Xian Jiang - West China Hospital
PubFacts is viewed by over 25,000 people per day (700,000 per month)!
Claim your profile, edit publications, view metrics, add additional information:
West China Hospital
Publications Authored By Xian Jiang
CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.
These miRNAs have been shown to be upregulated in sorafenib-resistant cells and participate in the mechanisms underlying sorafenib resistance. The AlncRNA contains tandem sequences of 6 copies of the complementary binding sequences to the target miRNAs and is expressed by an adenoviral vector (Ad5-AlncRNA). Infection of Ad5-AlncRNA into sorafenib-resistant HCC cells blocked the function of miRNAs, and sequentially inhibited the downregulation of PTEN and activation of AKT. Ad5-AlncRNA significantly inhibited proliferation and induced apoptosis of sorafenib-resistant cells and enhanced the effects of sorafenib in vitro and in animal models. Inhibition of autophagy decreased the sensitivity of sorafenib-resistant cells to Ad5-AlncRNA, while its induction had the opposite effect. These results indicate that targeting multiple miRNAs by the artificial lncRNA could be a potential promising strategy for overcoming sorafenib resistance in the treatment of HCC.
The smart integration of geometric and electronic effect confers a substantial enhancement of desired dehydrogenation pathway as well as electro-oxidation activity for the formic acid oxidation reaction (FAOR). We anticipate that the obtained nanocatalyst may hold great promises in fuel cell devices, and furthermore, the facile synthetic strategy demonstrated here can be extendable for the fabrication of other multicomponent nanoalloys with desirable morphologies and enhanced electrocatalytic performances.
The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook (v5.1.0). Meta-analysis was conducted using RevMan (v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI (1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI (0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI (0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI (0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI (0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.
PubMed, Embase, Cochrane Library, Scopus, Google Scholar and Research Gate were searched (from inception to April 2016). Primary outcome was operation time. Secondary outcomes were postoperative complications (anastomotic leak, stricture, bleeding, marginal ulcer and wound infection), percent excess weight loss during one-year follow-up, reoperation, and postoperative hospital stay. Odds ratios (OR) were calculated for dichotomous outcomes and mean differences (MD) for continuous outcomes.
Twelve trials were included comprising 13,626 patients (3309 hand-sewn vs. 6791 circular vs. 3526 linear). There was no difference in operation time when hand-sewn anastomosis was compared with mechanical gastrojejunostomy (MD, -6.00; 95% confidence interval (CI), -34.85 to 22.85; P = 0.68), circular stapled anastomosis (MD, -5.24; 95% CI, -32.71 to 22.24; P = 0.71) or linear stapled anastomosis (MD, - 3.75; 95% CI, -64.81 to 57.31; P = 0.90). Hand-sewn anastomosis had significantly lower incidence rate of postoperative bleeding (OR, 0.48; 95% CI, 0.31-0.74; P = 0.001) and wound infection (OR, 0.19; 95% CI, 0.08-0.45; P = 0.0002) than circular stapled anastomosis; there were no significant differences in the other secondary outcome. And there were no significant differences in all the comparable outcomes between hand-sewn anastomosis and linear stapled anastomosis.
This meta-analysis revealed no significant differences between mechanical and hand-sewn anastomosis except for greater incidence rates of postoperative bleeding and wound infection with the use of circular staplers. Besides, more trials with adequate power are required and a cost analysis also worth trying. REGISTRATION NO.
The cellular target of this small molecule was identified to be the succinate dehydrogenase subunit B (SDHB) protein of complex II of the mitochondrial electron transfer chain (ETC). The molecule protects the integrity of the ETC and allows treated cells to continue to proliferate after apoptosis induction. Moreover, this molecule blocked dopaminergic neuron death and reversed Parkinson-like behavior in a rat model of Parkinson's disease.
Stable transfectants, HCCC-HNF(low) and RBE-HNF(high), were generated from human CCA HCCC-9810 and RBE cells, respectively. The regulatory effect of HNF6 on miR-122 was evaluated by luciferase reporter assay. Cell proliferation, cycle distribution, migration and invasion were analyzed. The xenograft model was used to assess the effects of HNF6 overexpression on tumorigenesis, growth, metastasis and therapeutic potentials.
Human CCA tissues and cells expressed lower levels of HNF6, which positively correlated with miR-122. HNF6 regulated the expression of miR-122 by stimulating its promoter. HNF6 overexpression inhibited cell proliferation by inducing cell cycle arrest at G1 phase through regulating miR-122, cyclin G1 and insulin-like growth factor-1 receptor. HNF6 inhibited the migration and invasion of CCA cells by regulating matrix metalloproteinase-2 and metalloproteinase-9, reversion-inducing-cysteine-rich protein with kazal motifs, E-cadherin and N-cadherin. Co-transfection of anti-miR-122 abrogated the effects of HNF6. HNF6 overexpression inhibited the ability of cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors.
The results indicate that HNF6 may serve as a tumor suppressor by regulating miR-122, and its overexpression may represent a mechanism-based therapy for CCA.
Subjective assessment was made by both patients and dermatologists. Patients were also examined for evidence of complications. All patients experienced improvement (p < 0.05). There was no statistically significant difference between the two sides (p > 0.05). The pain after a short period of laser therapy was more severe for QS Alex than for QS Nd:YAG laser. Vesicles developed in 1 patient after QS Alex therapy. Both QS Alex laser and QS Nd:YAG laser were equally effective at improving bilateral nevus of Ota. Patients tolerate QS Nd:YAG laser better than QS Alex laser.
Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.
We found that ISL ameliorated the inflammatory process in psoriasis models but not in their respective controls. Moreover, the anti-inflammatory effects of ISL were attributed to the suppression of nuclear factor-κB (NF-κB) activity, which consequently resulted in the reduction of pro-inflammation cytokines IL-6 and IL-8 expression. In conclusion, ISL exhibited anti-inflammatory effects in psoriasis models, by downregulating IL-6 and IL-8 via suppression of NF-κB activity, suggesting that ISL might serve as a potential candidate for treatment of psoriasis and other autoimmune inflammatory diseases.
ISL could ameliorate the inflammatory process of psoriasis. ISL could suppress NF-κB and subsequent production of a series of pro-inflammatory cytokines. Dual-inhibitory activity against IL-6 and IL-8 of ISL is implemented via inhibiting NF-κB. ISL exerts no inhibitory effects on normal human keratinocytes or wild-type Balb/c mice, implying its low toxicity and safety.
The activated hypoxia-inducible pathways, which are mainly regulated by HIF-1, contribute to the resistance of hypoxic MTC cells to cabozantinib. Cabozantinib upregulated HIF-1α expression at translational levels and increased the expression of the downstream factors including VEGF, lactate dehydrogenase A (LDHA), HGF, and MET. 2ME2 corrected the activated pathways by cabozantinib through downregulating HIF-1α expression and inhibiting its nuclear translocation in hypoxic MTC cells. Administration of 2ME2 enhanced the efficacy of cabozantinib in suppressing the growth of MTC cell line xenografts and patient-derived xenografts established in mice. Given that 2ME2 targets insensitive hypoxic cancer cells to cabozantinib and can inhibit the activated pathways by cabozantinib, the present results warrant further investigation of 2ME2, particularly in combination with cabozantinib, for the treatment of MTC.
NRP-1 expression in clinical gastric cancer specimens was examined by immunohistochemistry and its association with clinicopathology analyzed. The expression of NRP-1 in a panel of human gastric cancer cells was examined by real-time RT-PCR and immunoblotting. Stable transfectants depleted of NRP-1, termed MGC-803-NRP(low), were generated from MGC-803 cells. Cell proliferation was analyzed by the Cell Counting Kit-8 and Bromodeoxyuridine incorporation assays, and migrating ability analyzed by migration assays. The xenograft model was used to assess the effects of NRP-1 depletion on tumorigenesis, growth, metastasis and therapeutic potentials. The role of NRP-1 as co-receptors in the signaling pathways stimulated by ligands was examined. The key molecules involved in cell proliferation, migration and related signaling pathways were detected by immunoblotting.
Gastric cancer tissues expressed higher levels of NRP-1 compared to normal gastric mucosa. Its expression correlated with clinical staging, tumor differentiation and pathological types. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest in the G1/S phase by upregulating p27, and downregulating cyclin E and cyclin-dependent kinase 2. NRP-1 depletion reduced the ability of cells to migrate by inhibiting the phosphorylation of focal adhesion kinase. NRP-1 depletion suppressed tumorigenesis, tumor growth and lung metastasis by inhibiting cell proliferation and tumor angiogenesis in situ. Therapeutic NRP-1 shRNA inhibited the growth of established BGC823 tumors. Depletion of NRP-1 inhibited the activation of VEGF/VEGFR2, EGF/EGFR and HGF/c-Met pathways stimulated by respective recombinant human VEGF-165, EGF and HGF proteins.
The present results indicate that NRP-1 may be a potentially valuable biomarker and therapeutic target for gastric cancer.
01 mM AS), and negative control group (without treatments). Cell proliferation was detected by CCK-8 assay. Apoptosis was analyzed by Hochest33342 staining and flow cytometry. Western Blot was carried out to detect the expression of Bcl-2 and Bax protein. Aβ1-42 treatment inhibited cell proliferation and increased cell apoptosis of HUVEC cells. Interestingly, AS at concentrations of 10 mM, 1 mM, 0.1 mM and 0.01 mM reversed the effects of Aβ1-42 by increasing cell survival rate and reducing apoptosis of HUVEC cells. Furthermore, the expression of Bcl-2 protein was increased whereas the expression of Bax protein was decreased in AS groups. Compared with Aβ1-42 group, the ratio of Bcl-2/Bax was significantly increased in AS groups (P < 0.05). These results suggested that AS may be effective in protecting cells from damage caused by aggregated Aβ1-42. And this effect may be attributed to the increase of Bcl-2 and decrease of Bax under AS treatment.
Akt and its downstream factors were highly activated and/or upregulated in sorafenib-resistant cells. Inhibition of autophagy decreased the sensitivity of sorafenib-resistant cells to sorafenib, while its induction had the opposite effect. Differential screening of miRNAs showed higher levels of miR-21 in sorafenib-resistant HCC cells. Exposure of HCC cells to sorafenib led to an increase in miR-21 expression, a decrease in PTEN expression and sequential Akt activation. Transfection of miR-21 mimics in HCC cells restored sorafenib resistance by inhibiting autophagy. Anti-miR-21 oligonucleotides re-sensitized sorafenib-resistant cells by promoting autophagy. Inhibition of miR-21 enhances the efficacy of sorafenib in treating sorafenib-resistant HCC tumors in vivo. We conclude that miR-21 participates in the acquired resistance of sorafenib by suppresing autophagy through the Akt/PTEN pathway. MiR-21 could serve as a therapeutic target for overcoming sorafenib resistance in the treatment of HCC.
First we used a microRNA (miRNA or miR) microarray to screen potential miRNAs whose expression can be altered by HDAC1 depletion. Of these miRNAs, miR-34a is important as it is often inactivated in cancer cells and acts as a tumor suppressor for various types of cancer. The reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) results confirmed that miR-34a was upregulated by HDAC1 knockdown. Cells depleted of HDAC1 had lower abilities to migrate, invade and adhere, which were restored by a miR-34a antagomiR. Depletion of HDAC1 also resulted in impaired microfilaments and microtubules, while co-transfection of the miR-34a antagomiR attenuated these changes in the cellular cytoskeleton. The HDAC1/miR-34a axis regulated the expression and activation of CD44 and its downstream factors including Bcl-2, Ras homolog family member A (RhoA), LIM domain kinase 1 (LIMK-1) and matrix metalloproteinase (MMP)-2. The latter three proteins were responsible for the organization of tubulin and actin cytoskeleton and the formation of cellular pseudopodia. In conclusion, results of the present study indicated that HDAC1 depletion inhibits the metastatic abilities of gastric cancer cells by regulating the miRNA-34a/CD44 pathway, which may be a potential target for the treatment of gastric cancer.
Ultrasound: On the right side of the upper cervical skin to submandibular gland rear could see tubular low echo area. MRI: Visible on the right side of the neck tube signal, after the submandibular gland rear. Three-dimensional CT: Visible on the right side of the neck by skin sinus crossings as deep as the tonsillar fossa lumen containing contrast agent. Clinical diagnosis: The second branchial cleft cyst and fistula.
A cohort of 88 paired of cervical cancer and the adjacent normal cervical epithelial tissues were collected. Quantitative RT-PCR (qRT-PCR) assay was used to detect the expression of miR-26b and its correlations with clinicopathological factors were statistically analyzed. Finally, the survival was assessed by the Kaplan-Meier method and proportional hazards model.
The expression level of miR-26b in cervical cancer tissues was significantly lower than that in the adjacent normal cervical tissues (P<0.001). Reduced miR-26b was observed to be significantly correlated with advanced FIGO stage, higher incidence of lymph node metastasis and recurrence of cervical cancer patients (P=0.002, 0.036 and 0.029, respectively). In addition, patients with low-miR-26b expression showed poorer recurrence-free survival (RFS) and overall survival (OS) than those with high-miR-26b expression (P=0.0043 and 0.0015, respectively). Furthermore, multivariate analyses demonstrated that low miR-26b expression was an independent prognostic factor for predicting the 5-year RFS and OS of cervical cancer patients (P=0.013 and 0.007, respectively).
Our results showed that reduced miR-26b was correlated with tumor development and poor prognosis in human cervical cancer. The status of miR-26b expression may be a potential prognostic biomarker for cervical cancer patients.
Compared to Sanger sequencing, good consistency was found between the results of the ARMS (Kappa = 0.839) and HRM (Kappa = 0.839). The sensitivities of the methods were compared after a consensus was reached: if two of the three methodologies showed a similar result, it was considered as the consensus result. The frequency of KRAS mutations in our population was 34.5%, and discordant findings were observed in five samples. No significant difference in sensitivity was found among the three methodologies.
From the results, we can conclude that after careful in-laboratory validation, HRM is a good alternative to the ARMS and Sanger sequencing for KRAS mutation testing.
The results have demonstrated that ATO synergized with sorafenib to inhibit the proliferation and promote the apoptosis of HCC cells by diminishing the increased activation of Akt by sorafenib. ATO was shown to inhibit the expression or activation of Akt downstream factors, including glycogen synthase kinase (GSK)-3β, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which regulate cell apoptosis and were upregulated or activated by sorafenib. Both sorafenib and ATO downregulated the expression of cyclin D1, resulting in HCC cells arrested at G0/G1 phase. ATO downregulated the expression of Bcl-2 and Bcl-xL and upregulated the expression of Bax, indicating that ATO could induce the apoptosis of HCC cells through the intrinsic pathways; but sorafenib showed little effects on these proteins of Bcl-2 family. ATO synergized with sorafenib to suppress the growth of HCC tumors established in mice by inhibiting the proliferation and inducing the apoptosis of HCC cells in situ. These results indicate that ATO may be a potential agent that given in combination with sorafenib acts synergistically for treating HCC.
The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.
The present study has demonstrated that sorafenib downregulated the expression of HIF-1α, making the hypoxic response switch from HIF-1α- to HIF-2α-dependent pathways, resulting in upregulation of HIF-2α, which contributes to the insensitivity of hypoxic HCC cells to sorafenib. HIF-2α played a dominant role in regulating VEGF, thus sorafenib in turn increased the expression of VEGF (a downstream molecule of both HIF-1 and HIF-2) and cyclin D1 (a downstream molecule of HIF-2), but reduced the expression of LDHA (a downstream molecule of HIF-1), in hypoxic HCC cells. 2ME2 significantly reduced the expression of both HIF-1α and HIF-2α, and their downstream molecules, VEGF, LDHA and cyclin D1, rendering hypoxic HCC cells to increased sensitivity to 2ME2. 2ME2 also inhibited the nuclear translocation of HIF-1α and HIF-2α proteins, but had no effect on their mRNA expression. 2M2 synergized with sorafenib to suppress the proliferation and induction of apoptosis of HCC cells in vitro and in vivo, and inhibited tumoral angiogenesis. These results indicate that 2ME2 given in combination with sorafenib acts synergistically for treating HCC.
The as-synthesized Pd tetrapods have a potential application in the formic acid (HCOOH)-induced reduction of highly toxic hexavalent chromium (Cr(VI)) owing to their improved catalytic performance for the HCOOH decomposition.
We report here the establishment of cell lines in which Bim or tBid can be inducibly expressed to initiate apoptosis in a controlled, quantitative manner. We used these cell lines to examine apoptotic events after Bax and Bak oligomerization but before cytochrome c release. The mitochondrial metalloprotease OMA1 was activated in this system in a Bax- and Bak-dependent fashion. Activated OMA1 cleaved the dynamin-like GTPase, optical nerve atrophy 1, an event that is critical for remodeling of mitochondrial cristae. Knockdown or knockout of OMA1 in these cells attenuated cytochrome c release. Thus it is clear that oligomerized Bax and Bak trigger apoptosis by causing both the permeabilization of the mitochondrial outer membrane and activation OMA1.
Fungal culture revealed light yellow filamentous colonies that were identified as Mucor irregularis by nucleotide sequencing of rRNA gene. Amphotericin B and dexamethasone were used in gradually increasing dosage. The treatment lasted 43 days, and the patient received 760 mg total amphotericin B. The patient was discharged after 2 months of treatment. The plaque became smooth, and fungal culture was negative. There was no recurrence for half a year through telephone follow-ups. A review of published studies revealed 23 cases of Mucor irregularis infection. Most cases resulted following injuries or surgical complications. Farmers and manual laborers were most at risk with males outnumbering females among patients. Amphotericin B and its liposomal preparations remain most effective treatment choices.
Expression of pERK increased significantly in the NTS in the control group following SNP infusion, and the expression peaked at 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than in control group. The BL group showed a relatively higher reduction in pERK expression than the SAD group, and the pERK expression in the NTS was localized to the caudal portion of the nuclei in the BL and SAD groups. These results suggest that the vestibular receptors may play a key role in maintaining blood pressure following acute hypotension; thus, the vestibular system may contribute to compensate for orthostatic hypotension.
Mice were pretreated with 5 or 45 mg/kg resveratrol for three days prior to bronchial perfusion with 25 mg/kg LPS. At 12 h after surgery, the ratio of the wet to the dry (w/d) lung was calculated to assess tissue edema. Histological changes of the lungs were detected using hematoxylin and eosin staining and the protein expression levels of TLR4, myd88 and nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF‑κB) were measured by western blot analysis. The concentration of interleukin (IL)‑6 and cyclooxygenase (COX)‑2 in the bronchoalveolar lavage fluid were detected by ELISA. The results showed that resveratrol can suppress the edema, inﬂammatory cell inﬁltration and alveolar structure damage of lungs in mice with ALI and decrease the lung w/d ratio. Additionally, resveratrol markedly decreased the expression of TLR4, myd88 and NF‑κB and decreased the concentration of inﬂammatory cytokines, including IL‑6 and COX‑2. Therefore, it can be concluded that resveratrol has a protective effect against ALI induced by LPS, at least in part by inhibiting the myd88‑dependent TLR4 signaling pathway. In conclusion, resveratrol pretreatment has a protective effect against LPS‑induced ALI in mice, which indicates that resveratrol may serve as a potential therapeutic agent for treating ALI in the clinic.
The as-prepared Pt NLAs are highly branched and three-dimensionally (3D) interconnected nanostructures, which are composed of many long Pt nanolances in various directions. PAH functionalization improves the electrocatalytic activity of the Pt NLAs for an oxygen reduction reaction (ORR) because of high interface proton concentration on the Pt surface and excellent anti-oxidation ability of the Pt nanolances. Meanwhile, the PAH molecules bound on the Pt NLAs surface act as barrier networks to restrain accessibility of alcohol, exhibiting a high ORR selectivity. In addition, the PAH functionalized Pt NLAs show excellent durability for the ORR due to their particular 3D interconnected structure. The work demonstrates that the PAH functionalized Pt NLAs are indeed promising cathodic electrocatalysts for practical application in direct alcohol fuel cells.
Two sorafenib-resistant HCC cell lines, which had been established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib-induced growth inhibition and apoptosis in vitro and in vivo. Sustained exposure to sorafenib activated Akt via the feedback loop of mTOR but independent of protein phosphatase 2A in HCC cells. Autophagy participated in the resistance to sorafenib as inhibition of autophagy reduced the sensitivity of sorafenib-resistant HCC cells to sorafenib, whereas activation of autophagy by rapamycin had the opposite effect. However, rapamycin did not show a synergistic effect with sorafenib to inhibit cell proliferation, while it also activated Akt via a feedback mechanism in sorafenib-resistant HCC cells. Inhibition of Akt reversed the acquired resistance to sorafenib by switching autophagy from a cytoprotective role to a death-promoting mechanism in the sorafenib-resistant HCC cells. Akt inhibition by GDC0068 synergized with sorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant feature in vivo. The results have provided evidence for clinical investigation of GDC0068, a novel ATP-competitive pan-Akt inhibitor, as the second-line treatment after the failure of sorafenib-medicated molecular targeted therapy for advanced HCC.
Sorafenib inhibits HIF-1α synthesis, making the hypoxic response switch from HIF-1α- to HIF-2α-dependent pathways and providing a mechanism for more aggressive growth of tumors. The present study has demonstrated that upregulation of HIF-2α induced by sorafenib contributes to the resistance of hypoxic HCC cells by activating the transforming growth factor (TGF)-α/epidermal growth factor receptor (EGFR) pathway. Blocking the TGF-α/EGFR pathway by gefitinib, a specific EGFR inhibitor, reduced the activation of STAT (signal transducer and activator of transcription) 3, AKT and ERK (extracellular signal-regulated kinase), and synergized with sorafenib to inhibit proliferation and induce apoptosis of hypoxic HCC cells. Transfection of HIF-2α siRNA into HCC cells downregulated the expression of VEGF (vascular endothelial growth factor), cyclin D1, HIF-2α and TGF-α, and inhibited the activation of EGFR. HIF-2α siRNA inhibited the proliferation and promoted the apoptosis of HCC cells in vitro, and synergized with sorafenib to suppress the growth of HCC tumors in vivo. The results indicate that targeting HIF-2α-mediated activation of the TGF-α/EGFR pathway warrants further investigation as a potential strategy to enhance the efficacy of sorafenib for treating HCC.
Expression of c-Fos protein increased significantly in the NTS in the sham group after sodium nitroprusside (SNP) administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared to that of the sham group. The SAD group showed relatively more reduction in c-Fos protein expression than the BL group, and the SAD+BL group showed the least expression among the three experimental groups. The c-Fos protein expression in the NTS following acute hypotension was localized to the caudal portions of the nuclei in the BL and SAD groups. These results suggest that the role of vestibular receptors in maintaining blood pressure following acute hypotension is less potent than that of the baroreceptors but more potent than other afferent inputs in conscious rats. In addition, afferent signals for maintaining blood pressure originating from the vestibular receptors and the baroreceptors may converge in the caudal portion of the NTS.
To compare the clinical outcomes of A-BPO combination gel with vehicle gel for treatment or maintenance therapy of patients with acne vulgaris.
An electronic search of the database PubMed (1966 to September 2012), Embase (1984 to September 2012), and Cochrane Controlled Trials Register (CENTRAL; 3rd Quarter, 2012) was undertaken to identify relevant studies. Main clinical outcomes were success rate, treatment-related adverse events (AEs), AEs leading to discontinuation, satisfaction with the effectiveness, and overall satisfaction.
Six studies were finally included in this meta-analysis. The A-BPO group yielded better clinical outcomes regarding the success rate (p<0.00001), satisfaction with the effectiveness of treatment (p=0.005), and overall satisfaction (p=0.005) compared to the vehicle group. The incidence of treatment-related AEs in the A-BPO group was comparable with that of vehicle group (p=0.09), while the A-BPO group was associated with a slightly increase in the incidence of AEs leading to discontinuation when compared with the vehicle group (p=0.02).
A-BPO combination gel yields better clinical outcomes including success rate, satisfaction with the effectiveness, and overall satisfaction compared to vehicle gel, despite an increased incidence of AEs leading to discontinuation. The A-BPO combination agent most likely contributes to the treatment of moderate acne vulgaris rather than severe acne vulgaris, but it may be useful in maintenance therapy of patients with severe acne vulgaris.
In contrast, down-regulation of survivin expression using small hairpin RNA (shRNA) vectors and the small-molecule inhibitor YM155, or inhibition of survivin function using a recombinant cell-permeable dominant-negative survivin protein (dNSur9), promoted CDDP-induced apoptosis. CDDP-resistant sub-lines generated from the parental SGC7901 and BGC823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF-1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (pAKT). Specific inhibition of AKT reduced the expression of HIF-1α and survivin, whereas specific inhibition or depletion of HIF-1α reduced survivin expression but had no effect on the expression of phosphorylated AKT. The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF-1α enhanced the sensitivity of CDDP-resistant cells to CDDP. Specific inhibition of survivin, AKT and HIF-1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up-regulation of survivin by AKT and HIF-1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.
0 cm size, lower limb reached 2.0 cm x 1.8 cm, the size of the mass on the left side of the supraclavicular reached 3.0 cm x 2.5 cm of the size of the mass, the three homogeneous medium hard, focally border and clear, the activity can be puncture cytological examination in return for: left supraclavicular see more protein and blood samples and a small amount of sample are arranged heap of fiber cells. Nuclear magnetic resonance (NMR): on the right side of the neck, with three at the left supraclavicular neoplasm, between 2.5-5.5 cm in size, high in T2, T1 low mixed signals, lesion boundaries clear.
The expression of DUOX2 protein was observed in all groups which mainly located in basal layer, spinous layer and dermal papilla layer. Compared with the psoriasis non-lesion group and normal skin group, the expression level of DUOX2 protein in psoriasis lesion group was significant higher (P<0. 01). The expression of DUOX2 protein in AD lesion group was stronger than that in AD non-lesion group and normal skin group (P<0. 01). In addition, the expression level of DUOX2 protein in AD lesion group was significant higher than that in psoriasis lesion group (P<0. 01). RT-PCR test revealed DUOX2 mRNA was expressed positively in psoriasis and AD lesions.
The strong expression of DUOX2 in psoriasis vulgaris lesion and AD lesion suggested that DUOX2 may play an important role in the mechanisms of cutaneous anti-inflammation.
Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.
Both cell lines endogenously secret IL-6, and blockage of IL-6 or JAK2 inhibited the activation of JAK2 and STAT3. Depletion of STAT3 downregulated Skp2 expression, and thereby increased the expression of p27 and p21. The depletion of STAT3 inhibited the ability of cells to migrate and invade, and impaired the cellular cytoskeleton mainly microtubules; while the depletion of p27 partially restored the impaired ability to migrate, and reversed the impaired microfilaments, further inhibited the ability to invade, but had little effect on microtubules and cellular adhering ability of STAT3-depleted cells. STAT3 depletion inhibited the activity of RhoA and the interaction with stathmin, downregulated the expression of pFAK (phosphorylated focal adhesion kinase), acetylated-tubulin, RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and Sp1, upregulated E-cadherin, and reduced the activities of MMP (matrix metalloproteinase)-2 and -9. The depletion of p27 increased RhoA (Ras homolog family member A) activity, upregulated RECK, and downregulated E-cadherin and Sp1 in STAT3-depleted cells. The results indicate that the interaction between STAT3 and Skp2/p27/p21 pathway plays an important role in mediating the motility, migration and invasion of gastric cancer cells, and inhibition of STAT3 may be a useful therapeutic approach for metastasis of gastric cancer, but caution needs to be taken for its effects on Skp2/p27/p21 pathway.
The protective function of PAH layers and enhanced antietching capability of Pd atom are responsible for the formation of the Pd icosahedra. Very importantly, the as-prepared PAH functionalized Pd icosahedra exhibit superior electrocatalytic activity and ethanol tolerant ability toward the oxygen reduction reaction (ORR) compared to the commercially available Pt black in alkaline media. At 0.95 V (vs RHE), the ORR specific kinetic current density at the Pd icosahedra is 4.48 times higher than that at commercial Pt black. The fact demonstrates the appropriate surface modification of the Pd nanoparticles by nonmetallic molecules can be regarded as an effective way to enhance the electrocatalytic activity toward the ORR.
In the proposed PAH-K(2)PtCl(4)-HCHO synthesis system, the raw material could be reutilized to re-synthesize the Pt-NCs, and the particle size of the Pt-NCs could be readily controlled by the reduction rate of the Pt(II) species in the Pt(II)-PAH complex. After UV/Ozone and electrochemical cleaning, the residual PAH on the Pt-NC surfaces still strongly influenced the d-band centre of Pt due to the strong N-Pt interaction. The as-prepared 6 nm Pt-NCs showed superior electrocatalytic activity (mass activity and specific activity) and stability towards the oxygen reduction reaction (ORR) in both H(2)SO(4) and HClO(4) electrolytes compared to the commercial E-TEK Pt black, owing to the combination of the facets effect and electronic effect.
In contrast, Skp2 shRNA had only a slight effect on the above properties of BGC823 cells, which express a low level of Skp2. In accord, knockdown of Skp2 suppressed the ability of MGC803 cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors, by inhibiting cell proliferation and enhancing cell apoptosis. In contrast, overexpression of Skp2 promoted tumorigenesis of BGC823 cells in mice. Skp2 depletion induced cell cycle arrest in the G(1)/S phase by upregulating p27, p21, and p57 and downregulating cyclin E and cyclin-dependent kinase 2. Skp2 depletion also increased caspase-3 activity, impeded the ability of cells to form filopoidia and locomote, upregulated RECK (reversion-inducing cysteine-rich protein with kazal motifs), and downregulated matrix metalloproteinase (MMP)-2 and MMP-9 activity and expression. The results suggest that downregulating Skp2 warrants investigation as a promising strategy to treat gastric cancers that express high levels of Skp2.
Primary cultured human skin fibroblasts were irradiated with different doses of UVA light. Cell viability, cell cycle phase, β-galactosidase, and the length of telomeres were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, cytochemical staining, and real-time polymerase chain reactions, respectively.
After UVA irradiation, inhibited proliferation, S phase accumulation and increased expression of senescence-associated β-galactosidase were observed in cultured fibroblasts. Moreover, the length of telomeres in UVA-treated cells was shortened in a dose-dependent manner as compared to controls (p < 0.05).
These results suggest that telomere length in human dermal fibroblasts can be shortened by a single high dosage of UVA radiation, and that acute photodamage might contribute to early photoaging in human skin via rapid telomere shortening. This study potentially provides the basis for better understanding of the molecular mechanism of photoaging.
The autoimmune-mediated apoptosis of melanocytes might be an important part of the etiology of vitiligo, which prevents the formation of melanocytes in the skin. Here we propose a novel hypothesis for vitiligo treatment using in situ melanocyte regeneration induced by melanocyte-lineage-specific genes (MLSGs). This may serve as an intelligent bioengineering prototype. The hypothesis is based on the fact that MLSGs regulate melanocyte differentiation through epigenetic reprogramming, which includes microphthalmia-associated transcription factor (MITF), paired box 3 (PAX3), and Notch signaling. MITF directs the terminal differentiation of melanocytes, and PAX3 helps to establish the properties of the melanocyte stem cells. Notch signaling promotes adult stem cell proliferation and self-renewal. This process could be mimicked by Notch intracellular domain (NICD). MLSGs could also stimulate anti-apoptotic gene expression. Recent improvements in relevant biotechniques allow the transdermal delivery of MLSG proteins into the patient, where they enter cells through protein transduction. This process may promote melanocyte regeneration in situ with little impact on the hair follicular cycle or on carcinogenesis. This simple and efficient treatment may have significant impact on the treatment of vitiligo patients.
Compared with the control group, each the number of intracellular viable bacteria did not change significantly under the condition of 20 ng/mL of either TNF-alpha or IFN-gamma (P > 0.05), as well as 40 ng/mL of TNF-alpha (P < 0.05). However, it was reduced significantly after the addtion of 40 ng/mL of IFN-gamma (P < 0.05), while was also decreased by the combination of TNF-alpha and IFN-gamma, of which effect was less than that achieved by IFN-gamma alone (P > 0.05).
IFN-gamma, not TNF-alpha, can enhance the bactericidal function of keratinocytes, and the bactericidal effect, is weaker when treatment is combing IFN-gamma with TNF-alpha.
The aim of the present study was to determine whether transfection of siRNA targeting HIF-2α could enhance the efficacy of doxorubicin, the most commonly used drug in the treatment of HCC. Transfection of HIF-2 siRNA into human HCC cells downregulated the expression of HIF-2α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α, and cyclin D1, but had little effect on the expression of HIF-1α, fms-related tyrosine kinase-1 (Flt-1), the glucose transporter (GLUT)-1, and lactate dehydrogenase A (LDHA). Doxorubicin itself only downregulated VEGF expression. Furthermore, HIF-2 siRNA inhibited proliferation, induced cell cycle arrest at the G(0)/G(1) phase, and acted synergistically with doxorubicin to inhibit the growth of human HCC cells in vitro. Transfection of HIF-2 siRNA also downregulated tumoral expression of HIF-2α, VEGF, TGF-α, and cyclin D1 in vivo, and acted synergistically with doxorubicin to suppress the growth of HepG2 tumors established in immunodeficient mice by inhibiting cell proliferation, tumor angiogenesis and microvessel perfusion. The results of the present study suggest that targeting HIF-2α with siRNA warrants investigation as a potential strategy to enhance the efficacy of doxorubicin in the treatment of HCC.
Sodium hydrosulfide (NaHS), a donor of H(2)S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine γ-lyase (CSE), were applied to the rats to investigate the effects of H(2)S on CCl(4)-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2)S, hepatic H(2)S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4) significantly reduced serum levels of H(2)S, hepatic H(2)S production and CSE expression. NaHS attenuated CCl(4)-induced acute hepatotoxicity by supplementing exogenous H(2)S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters.
Exogenous H(2)S attenuates CCl(4)-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2)S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.
The survival, HO-1 activity, Banff rejection activity index, serum levels of IL-2 and TNF-α, infiltration of CD4(+), CD8(+), and T(reg) (CD4(+)CD25(+)Foxp3(+)) cells into donor livers, and expression of Foxp3, TGF-β, and IL-10 were examined. A mixed lymphocyte reaction (MLR) was performed.
Intraportal delivery of AAV-HO-1 resulted in persistent expression of HO-1 and increased activity of HO-1 in transplanted livers, leading to prolonged survival of recipients. Overexpression of HO-1 reduced the Banff rejection activity index, and production of IL-2 and TNF-α, inhibited infiltration of CD4(+) and CD8(+) cells, and increased infiltration of T(reg) cells, into donor livers. The spleens of recipients expressed higher levels of Foxp3, TGF-β, and IL-10 than those of control rats, and the transplanted livers expressed higher levels of Foxp3 and TGF-β. Splenocytes from the tolerant recipients had higher percentages of T(reg) cells, and responded poorly to the allogeneic donor splenocytes.
Persistent expression of HO-1 in donor livers by intraportal delivery of AAV-HO-1 improves the survival by expanding T(reg) cells. HO-1-based therapies, as described herein, promise new strategies to prevent the rejection of liver transplants.
Reverse transcription-polymerase chain reaction and immunohistochemistry (IHC) were used to examine HLA-G expression in normal mammary and breast cancer cell lines and normal and human breast cancer tissues. Reverse transcription-polymerase chain reaction confirmed that normal epithelial MCF-12A cells had no HLA-G mRNA expression, whereas cancer cell lines MCF-7, T47D, and MDA-MB-231 and NCI/Adr-Res had various levels of HLA-G mRNA expression. Twelve (12) normal and 38 breast cancer tissues were examined by IHC. Fifty-eight (58) percent (22/38) of cancers had medium to strong staining to HLA-G, whereas only 8% (1/12) of normal breast tissues had medium to strong staining, and the difference was significant (p < 0.05). HLA-G staining was found in the membranes and cytoplasm of cancer cells. In conclusion, breast cancer cells overexpress HLA-G mRNA and protein, and this probably contributes to immune evasion.
We performed intra-cardiac injection in nude mice to explore bone metastatic ability of different cell lines. The results showed that knockdown of BSP significantly inhibited the proliferation of MDA-MB-231BO cells and their adhesion to bone matrix. We also observed bone destruction caused by bone resorption around some adhering cells. The appearances of the cells changed in BSP gene silenced group, and the secretion of TGF-beta1 and RANKL decreased. The results showed BSP gene silence can partial inhibition bone metastasis of breast cancer cells in nude mice by X-ray assay and hematoxylin-eosin staining. Based on our research, siRNA-mediated BSP silencing can inhibit proliferation and adhesion to bone matrix of bone-seeking breast cancer cells and change their surface structure, thus inhibits their bone metastatic ability.
The present study aimed to investigate effect of pretreatment with propofol on the ketamine-induced rapid antidepressant-like action in rats receiving forced swimming test. Open field test and forced swimming test were used to investigate behavior changes of rats receiving different medication. Expression of brain derived neurotrophic factors (BDNF) and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) pGluR1-Ser845 in hippocampus was measured with sandwich-ELISA and Western Blot, respectively. Results demonstrated that rats receiving propofol alone showed neither antidepressant-like effects nor increased BDNF content; pretreatment with propofol could increase the ketamine-induced antidepressant-like effects and the expression of AMPA pGluR1-Ser845 in hippocampus, but could not further reinforce the increased BDNF content induced by ketamine in hippocampus; after AMPA receptor was antagonized, the strengthening effect of propofol on ketamine-induced antidepressant-like action significantly decreased. The results indicated that propofol in a sub-anesthetic dose could increase the ketamine-induced antidepressant-like effect.
5 J/cm2 UVA affect the proliferation, collage protein, SOD and GSH-Px activity in the fibroblast cells (P < 0.05). Sodium selenite (10-100 microg/L) and aloin (1-100 mg/L) could enhance the proliferation and the SOD and GSH-Px activity. A increased collagen synthesis in dose dependant manner was also observed (P < 0.05).
Sodium selenite and aloin in a certain range of concentration have protective effects on ultraviolet radiation induced fibroblast proliferation inhibition, oxidative injury, and decreased collagen synthesis.
Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.
The cells were subjected to adhesion, migration or invasion assays, and co-cultured with human lung tissues in a microgravity rotary cell culture system to examine cellular infiltration in situ. ATRA-differentiated cells expressed high levels of CXCR4, and adhered more strongly to matrigel. Their ability to migrate and invade was enhanced by SDF-1alpha and lung homogenate, and diminished by pre-treatment with an anti-CXCR4 blocking antibody. SDF-1alpha was expressed in the lung tissues of all seven human donors. ATRA-differentiated NB4 cells infiltrated into lung tissues, and this was reduced by pre-treatment with an anti-CXCR4 blocking antibody. The interaction of SDF-1alpha and CXCR4 plays an important role in pulmonary cellular infiltration during DS, suggesting that targeting SDF-1alpha and CXCR4 may provide the basis for potential treatments in the management of DS.
We found the following: i) the MCF-7 cells have higher expression of TFRC and SLC11A2 compared with MCF-12A epithelia; ii) SLC40A1 was only expressed in MCF-12A epithelia but not in MCF-7 cells; iii) iron increased mRNA levels of the SLC11A2 gene in both MCF-12A and MCF-7 cells; iv) TFRC antisense oligonucleotides reduced TFRC mRNA levels and intracellular total iron, and inhibited the proliferation of the 4T1 cells in cell culture; v) TFRC antisense oligonucleotide inhibited tumor growth and lung metastases in the 4T1 mammary adenocarcinoma mouse model. In conclusion, breast cancer cells up-regulate the expression of iron importer genes and down-regulate the expression of iron exporter SLC40A1 to satisfy their increased demand for iron. Suppression of transferrin receptor by antisense results in inhibition of tumor growth and lung metastasis in the 4T1 mammary adenocarcinoma mouse model.
5 mmol/L 5-ALA did not affect the proliferation, melanogenesis and tyrosinase activity in B16 melanoma cell. The cell yielding in UVA group increased significantly (P < 0.05) compared with that of negative control group after UVA irradiation (3, 4 J/cm2), but the proliferation of the treated B16 cells were suppressed after UVA irradiation (5 J/cm2). IPL (20, 30, 40 J/cm2) or IPL plus ALA did not have any significant effects on cell proliferation. IPL or IPL plus ALA have inhibitory effects on melanogenesis without any influence on cell tyrosinase activity in B16 cells. ALA, as the photosensitizer, combined with IPL could have stronger effect than IPL alone.
We demonstrated that UVA could stimulate the proliferation of B16 cells, increase the melanogenesis and tyrosinase activity of the cells. IPL or IPL plus ALA have inhibitory effects on melanogenesis without any influence on cell proliferation and tyrosinase activity in B16 cells. IPL plus ALA had stronger effect than IPL alone.
The optimum condition of time and temperature was approached using temperature of 41 degrees C, 42 degrees C, 43 degrees C, 44 degrees C and 45 degrees C, and time of 0.5 h, 1.0 h, 1.5 h, 2.0 h and 2.5 h to induce HSV-2 reactivation. The optimum concentration of Forskolin was also decided using 25, 50, 75, 100 and 125 micromoL/L to activate the virus from latency. PCR was used to authenticate HSV-2 latent infection and reactivation. The morphological changes were observed when the virus was reactivated from latency.
The optimum concentration of ACV was 60 micromoL/L to establish latency in SH-SY5Y cells. Suitable infective dose of HSV-2 was 1-10 MOI to construct latency and reactivation in SH-SY5Y cells. The time of virus latency in SH-SY5Y cells could reach up to 14 d. Heat stress of 43 degrees C, 1.5 h and 75 micromoL/L Forskolin were the optimum condition to induce virus reactivation. The morphologic changes in SH-SY5Y cells recurred by HSV-2: Cytopathic effects-were more and more obvious with time lasting from 24 h to 72 h after reactivation from latency. PCR and results of electrophoresis proved the cell model of latent infection and reactivation was set up successfully.
The cell model system of HSV-2 latent infection and reactivation in SH-SY5Y cells was established. The research provided usefulness for study on HSV-2 of latency, reactivation and pathogenic mechanism.
The shRNA expression vectors targeting human Del1, and vascular endothelial growth factor (VEGF) were constructed. Gene transfection of Del1-shRNA downregulated expression of Del1 in LS-174T cells in vivo and in vitro, but did not alter the proliferative or survival properties of cells in vitro. Gene transfection of VEGF-shRNA downregulated expression of both VEGF and Del1 in LS-174T cells in vivo and in vitro. Both Del1-shRNA and VEGF-shRNA gene therapies exhibited anti-tumor activities and they also showed a synergistic effect in suppressing growth of colon tumors by anti-angiogenesis and anti-proliferation. Although further investigation to clarify the mechanisms explaining the role of Del1 in tumor growth, and the interaction between VEGF and Del1, is required, the results indicate that downregulation of Del1 presents a potent therapeutic strategy to combat colon cancer.
A kallistatin expression plasmid was constructed and its expression was detected after intratumoral gene transfer. Both kallistatin gene therapy and meloxicam suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and the combinational therapy showed a stronger effect in suppressing tumor growth, tumor angiogenesis and cell proliferation, and increasing cell apoptosis, than the respective monotherapies. Gene transfer of kallistatin inhibited tumor angiogenesis, and slightly inhibited cell proliferation and increased cell apoptosis in situ, but had no effect on expression of vascular endothelial growth factor, basic fibroblast growth factor, proliferating cell nuclear antigen, Bcl-2, Bax, or activation of caspase-3. Meloxicam therapy inhibited cell proliferation, induced cell apoptosis, reduced expression of proliferating cell nuclear antigen, increased activation of caspase-3, and upregulated Bax. Meloxicam also slightly inhibited tumor angiogenesis with no effect on the expression of vascular endothelial growth factor or basic fibroblast growth factor. Combining two novel anticancer agents, kallistatin targeting tumoral vascularization and meloxicam targeting cell proliferation and apoptosis, warrants investigation as a therapeutic strategy to combat HCC.
Intraportal delivery of AAV-ASHIF led to long-term localized expression of transgenic ASHIF in rat liver, and suppressed the growth of CBRH7919 HCC tumors established in rat liver by inhibiting the formation of neovessels and tumor cell proliferation. TAE therapy caused the necrosis and shrinkage of liver tumors; however, neovessels quickly formed and the residual tumors underwent rapid expansion. TAE enhanced tumor and liver hypoxia, which in turn upregulated expression of HIF-1alpha, vascular endothelial growth factor, glucose transporter-1, lactate dehydrogenase A, and proliferating cell nuclear antigen. Intraportal injection of AAV-ASHIF augmented the therapeutic effects of TAE and diminished its undesirable effects, resulting in extensive tumor cell death and suppression of the growth of liver tumors. In conclusion, this study has revealed that HIF-1 impedes the response of liver tumors to TAE. Antisense HIF-1alpha therapy is warranted as an approach for enhancing the efficacy of TAE to treat unresectable liver cancers.
The aim of the present study was to determine whether gene transfer of antisense HIF-1alpha could enhance the therapeutic efficacy of doxorubicin to combat HCC. Both antisense HIF-1alpha therapy and doxorubicin suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, tumor angiogenesis, and cell proliferation, and induced tumor cell apoptosis. The combination therapy with antisense HIF-1alpha and doxorubicin was more effective in suppressing tumor growth, angiogenesis, and cell proliferation, and inducing cell apoptosis than the respective monotherapies. Gene transfer of antisense HIF-1alpha downregulated the expression of both HIF-1alpha and VEGF, whereas doxorubicin only downregulated VEGF expression. Antisense HIF-1alpha and doxorubicin synergized to downregulate VEGF expression. Both antisense HIF-1alpha and doxorubicin inhibited expression of proliferating cell nuclear antigen, and combined to exert even stronger inhibition of proliferating cell nuclear antigen expression. Antisense HIF-1alpha therapy warrants investigation as a therapeutic strategy to enhance the efficacy of doxorubicin for treating HCC.
The overlapping PCR extension and restriction enzyme-digestion were used to generate DNA fragments encoding designed shRNA based on sequences of ORF C of HBV genome. The pU6 derived vectors were constructed to develop plasmid based shRNA delivery systems termed pU6/HBVi. There were significant reductions in the expression of HBsAg and HBeAg between cells transfected with pU6/HBVi and control groups (as to HBsAg: P < 0. 01; and HBeAg: P < 0. 01). Consistently, the HBV DNA copies were reduced from 2.71 x 10(7) to <5 x 10(2) copies with or without pU6/HBVi. These results suggested that shRNA delivery by recombinant plasmids harboring shRNA encoding DNA fragment of interest generated either by overlapping PCR extension or restriction enzyme-digestion, could inhibit expressions of viral proteins and reduce viral replications. The pU6 derived plasmids might be a useful shRNA delivery system in mammalian cells. In addition, we found siRNA based on stealth 2311 was a potent RNAi target of HBV genome.
The experimental design consisted of three groups of 24 Wistar rats each: a sham-operation group (control group), a group subjected to intestinal I/R and then given saline (saline group), and a group subjected to intestinal I/R and then given oxymatrine (oxymatrine group). Intestinal I/R was induced by occluding the superior mesenteric artery for 45 min. Six rats from each group were killed at selected time points, and blood and intestinal samples were collected.
Morphological alteration, reduction of gamma-glutamyl transpeptidase (gamma-GGT) activity, and increased cell apoptosis confirmed intestinal I/R injury. The oxymatrine group had a significantly lower histological score and apoptosis index than the saline group, demonstrating that the preadministration of oxymatrine attenuated gut damage. Moreover, oxymatrine inhibited the production of lipid peroxides (LPO), decreased the serum levels of tumor necrosis factor (TNF)-alpha, and downregulated expression of phosphorylated p38 mitogen-activated protein kinase, Fas, and FasL, which had been elevated by I/R.
These results provide further evidence of the anti-inflammatory and anti-apoptotic activities of oxymatrine, which may become a potent drug for protecting the intestines against I/R injury.
Enterobacteia repetitive intergenic consensus sequences were used as primers to amplify the target sequences in S. typhimurium genomic DNA: Amplification products were separated by agarose gel electrophoresis, and electrophoresis maps were analyzed by gel image analysis system. To optimize template concentration, Mg2+ concentration, primers concentration and annealing temperature of PCR, the factor to be optimized was designed in different concentration grads and other factors were fixed. Analyzed 16 Salmonella strains and one E. coli strain by PCR conditions optimized.
The electrophoresis bands of amplified products were entire and most clear when template concentration was 100 ng/25 microl, Mg2+ concentration was 2.0 mmol/L, primers concentrations were 0.4 micromol/L respectively in the total volume of 25 microl of the reaction system, and annealing temperature was 52 degrees C. The ERIC-PCR fingerprint maps of different Salmonella strains with different sources were different. From 250 to 5000 bp, there were 3 to 13 bands, and in those there was a specific 250 bp band.
Important reaction conditions of ERIC-PCR had been optimized in this study. ERIC-PCR technique could discriminate Salmonella strains isolated from different regions. It could be used in Salmonella epidemiology investigation and homology tracing, so as to make up for the flaws of the traditional classification methods for salmonella.
The fused protein angiogenin-EGF was then expressed in HUVECs, and the subcellular localization of the recombinant protein was determined by confocal microscopy and TEM assay. Recombinant angiogenin was found to mainly concentrate in the pars granulosa of the nucleus, where the protein accumulates to form ribonucleoprotein particles.
Virus particles were purified by heparin column chromatography and titre were detected by Real-time PCR. An orthotopic liver transplantation model by Wistar to Wistar was set up using Kamada's two cuff technique. Purified rAAV-GFP was injected into portal vein and incubated for 2 hours at the donor liver cold preserved stage, and then performed OLT. Recipients were killed and visceral organs were sampled at 1 and 3 months after operation respectively, frozen section (3-5 microm) were prepared and gene expression rate in different tissues was examined under fluorescence microscope.
The inserted segment of HO-1 was identified through restriction enzyme cutting followed with electrophoresis, the result of DNA sequencing was in accordance with which found in Genbank. The GFP expression rate was over 80% in allograft at 1 and 3 month after transfection whereas there was no GFP expression in heart, lung, spleen, kidney and small bowel.
High titre rAAV carried HO-1 and GFP were constructed successfully. Steady and effective expression of GFP mediated by rAAV was demonstrated in liver allograft in rats.
ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial cells, and there was a positive correlation between the level of ODC mRNA and the staging of tumors. The expression of ODC correlated with cyclin D1, a cell cycle protein, in synchronized breast cancer MDA-MB-231 cells. Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression of ODC and cyclin D1, resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase, and the inhibition of colony formation, an anchorage-independent growth pattern, and the migratory ability of MDA-MB-231 cells. rAd-ODC/Ex3as also markedly reduced the concentration of putrescine, but not spermidine or spermine, in MDA-MB-231 cells. The results suggested that the ODC gene might act as a prognostic factor for breast cancer and it could be a promising therapeutic target.
1) was constructed, which produced intense expression of endostatin and inhibited angiogenesis in the chorioallantoic membrane assay. 4T1 breast tumors were established in BALB/c mice by subcutaneous injection of 1 x 10(5) 4T1 cells. The End-pcDNA3.1 plasmid diluted in the transfection reagent FuGENE was injected into the tumors (around 100 mm(2)), and paclitaxel was injected i.p. into the mice. Endostatin gene therapy synergized with paclitaxel in suppressing the growth of 4T1 tumors and their metastasis to the lung and liver. Both endostatin and paclitaxel inhibited tumor angiogenesis and induced cell apoptosis. Despite the finding that endostatin was superior to paclitaxel at inhibiting tumor angiogenesis, paclitaxel was nevertheless more effective at inducing tumor apoptosis. The combination of paclitaxel and endostatin was more effective in suppressing tumor growth, metastases, angiogenesis, and inducing apoptosis than the respective monotherapies. The combinational therapy with endostatin and paclitaxel warrants future investigation as a therapeutic strategy to combat breast cancer.
The plasmid designated pU6B/HBVi was transfected into 2.2.15 cells using Lipofectamine 2000 reagent. The HBsAg and HBeAg in the supernatants of the transfected cells were measured by ELISA. The HBV copies in the transfected cells were measured by quantitative PCR.
Compared with controls, not only concentration of HBsAg and HBeAg but also HBV copies in transfected 2.2.15 cells decreased significantly by the plasmid expressing shRNA against HBV.
HBV replication and expression in 2.2.15 cells are inhibited by stably expressed shRNA.
IGF significantly promoted proliferation of SW-13 cells, and its effect was positively correlated with its concentrations (P<0.05). IGF receptor-I antibody inhibited the effect of insulin-like growth factor with direct inhibitory effect on proliferation of SW-13 cells (P<0.05).
IGF can promote the growth of human adrenocortical carcinoma SW-13 cells via its receptor-I. IGF receptor-I antibody can inhibit the effect of the growth factor, suggesting a possible role of this receptor in the treatment of adrenocortical carcinoma.
The mean level of serum ANG in untreated NPC was (371.4 +/- 123.5) microg/L, which was significantly higher than that in healthy controls(292.5 +/- 74.2) microg/L (P < 0.01). Furthermore, the serum level of ANG increased with the development of tumor (P < 0.05). After treatment, all patients reached a response: partial response (PR) or complete response (PR), and the serum ANG level was (340.6 +/- 112.4) microg/L, which was significantly lower than that in untreated ones (P < 0.05), but still higher than that in healthy controls (P < 0.05).
Our results indicate that the serum ANG level increases in patients with NPC, and is correlate with primary tumor progression.
01). The level of IL-8 was increased 1 h after the irradiation of 30 mJ/cm2 UVB, and it reached the peak at 12 h. There was statistically significant difference between the IL-8 levels detected at different times (3 h, 6 h, 12 h, 24 h after irradiation) and that at 0 h (P<0.01).
UVB increase the secretion of IL-8, and the effect is dose-dependent to some extent.
He was treated with broad-spectrum antibiotics after hospitalization but the nodule formed a large abscess and then a deep ulcer instead of resolving. Examination of the culture by light microscopy revealed ovoid budding yeasts displaying collar-shaped structure. Subculture of the primary colonies onto Sabouraud's dextrose agar and medium containing rapeseed oil resulted in growth only on the medium containing rapeseed oil. All of the isolates was identified as Malassezia furfur. The pathogenicity of the isolates was tested in mice by intravenous injection of (3-5) x 10(8) cfu per mouse after immunosuppression with 500 mg/kg of prednisone intraporitoneally on day-2. In the mouse model, micro-abscess and inflammatory reaction and oval yeasts with budding were noted in histopathologic section of the viscera of the mice. A rib-like or serrate-like structure of the inner side of cell wall, characteristic for Malassezia spp., was observed by transmission electron microscopy. The patient received oral fluconazole and topical amphotericin B. The isolate before antifungal therapy was sensitive to both fluconazole and amphotericin B, while the isolate after antifungal treatment was only sensitive to amphotericin B. Proteinase activity of the isolates increased 1.43 times after antifungal treatment. This case indicated the invasive power of M. furfur in deep infection. Renal transplantation and reception of long-term immunosuppressive treatment are risk factors for the invasive infection of this fungus.
Though this is a most important property and a most basic parameter in colloid interface electrochemistry, no reliable method for its determination is available yet. In the present paper, based on the diffuse double-layer theory, mathematical relations are constructed between the average concentration of ions positively adsorbed in the diffuse double layer and the surface potential of solid particles, thus transforming the determination of surface potential of solid particles into that of the average concentration of ions in the diffuse double layer, and then by applying the standard relationships of Gouy-Chapman theory, the mathematical relations of the average concentration of ions in the diffuse double layer with surface charge density, electrical field strength at surface, and specific surface area of solid particles are constructed.
Surface makers on treated HL-60 cells were analyzed by flow cytometry. The proliferation of allogeneic human T cells was detected by MTT colorimetry.
Under the condition of a suitable dose (200 microg/L) of A23187 treatment of HL-60 cells for 24 hours, the expression of CD83 molecule, a characteristic marker on DCs, was highest. The typical dendritic outgrowth appeared at a time when HL-60 cells were treated with A23187 for 72 hours. However, when HL-60 cells were treated with A23187 for 96 hours, the expressions of CD80 (B7.1), CD86 (B7.2), MHC-class II molecule and CD54 on HL-60 cells reached peak, and marked activation of allogeneic T cells occurred.
Calcium ionophore A23187 can induce the HL-60 cells to differentiate into activated DCs-like cells.
Cooperation effect was showed when three different concentration chymopapain combined with PYM during 48 hours. It accorded with the change of enzyme activity of chymopapain in saline water. Cooperation effect was showed again when adding chymopapin for the second time at 48 hours.
Chymopapain has cytotoxicity on hepa-6 in vitro. Cooperation effect was showed when chymopapin was combined with PYM.
The protein (P5-StxA) was expressed in E. coli.
ELISA and Western blot were applied to characterize the binding interaction between the fusion protein, P5-StxA and KDR. Cytotoxicity assay showed that P5-StxA maintained similar toxicity to cell as StxA. In the model of angiogenesis, P5-StxA inhibited selectively VEGF-induced growth of preexisting vessels of the chick chorioallantoic membrane.
These studies demonstrate the small peptide, P5, maybe be used as carrier of toxin targeting to KDR.
The recombinant plasmid was transfected into the human umbilical vein endothelial cells (HUVECs) via Lipofectin transfection. The expression of ANG gene in transfected HUVECs was detected by fluorescence microscopy and immunohistochemical staining.
DNA sequencing showed the sequence of the synthetic ANG was correct and amino acid sequence of ANG was right. The green fluorescence could be seen in transfected HUVECs under fluorescence microscope. Immunohistochemical staining detection showed that ANG expressed in transfected cells.
Human ANG full-length cDNA has been obtained. The ANG protein was expressed in mammalian cells successfully.
The apoptosis, caused by deferoxamine mesylate, and gallium or indium bound to transferrin in the MCF-7 cells, can be completely inhibited by excess ferric chloride or equimolar iron-loaded transferrin. Gallium-transferrin and indium-transferrin complexes induced more apoptosis than their respective salts in the MCF-7 cells. Deferoxamine mesylate induced a small increase in the endogenous expression of both the bcl-2 and bax genes in the MCF-7 cells and this can be prevented by ferric chloride. In the 13762NF rat mammary adenocarcinoma model, in situ TUNEL assays showed that the iron-deficiency following a low iron diet or intravenous injection of deferoxamine mesylate produced 5.32 +/- 3.90% and 6.46 +/- 3.58% of apoptotic cells, respectively, compared to 2.01 +/- 1.20% of apoptotic cells in the control rats maintained on a normal diet (p < 0.05 and p < 0.01, respectively, Student's t-test). This is the first report of iron depletion caused by a low iron diet or deferoxamine mesylate treatment inducing apoptosis in rats bearing the 13762NF marnmary adenocarcinoma.
Five specific binding positive target molecule phage clones were obtained which were able to bind to cells whose surface had high KDR, among which, clone 3 and 13 could effectively block the vascularization of the chorioallantoic membrane of chick embryo, but they were not inhibitive on the proliferation of high KDR expression cells.
The peptides, being the inhibitors of VEGF, may be useful in the treatment of cancers.
T cells induced by DCs transfected with rV-CEA showed specific cytotoxicity against CEA-secreting tumor cells.
DCs transfected with rV-CEA can elicit activation of CEA-specific T cells.
The PHA-LAK cell activity on 143TK could reach 57.3% when the ratio of effective cell (EC) to target cell (TC) was 7.5:1. The antitumor effect did not increased or even decreased when the ratio of EC to TC was 15:1. CONCLUSIONS: (1)PHA-LAK cell has non-specific cytotoxicity against tumor cells and can overcome the problems of the quantity and activity of immunocyte of traditional adoptive cellular immunotherapy. (2)Under some conditions does MTT colorimetric assay be a susceptible, simple and convenient method for detecting the cytotoxicity of immunocytes.