Publications by authors named "Jian He"

917 Publications

Effectively Intervening Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells With a Combination of ROCK and TGF-β Signaling Inhibitors.

Invest Ophthalmol Vis Sci 2021 Apr;62(4):21

Department of Ophthalmology of Shanghai Tenth People's Hospital, and Tongji Eye Institute, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, China.

Purpose: Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key pathological event in proliferative retinal diseases such as proliferative vitreoretinopathy (PVR). This study aimed to explore a new method to reverse EMT in RPE cells to develop an improved therapy for proliferative retinal diseases.

Methods: In vitro, human embryonic stem cell-derived RPE cells were passaged and cultured at low density for an extended period of time to establish an EMT model. At different stages of EMT after treatment with known molecules or combinations of molecules, the morphology was examined, transepithelial electrical resistance (TER) was measured, and expression of RPE- and EMT-related genes were examined with RT-PCR, Western blotting, and immunofluorescence. In vivo, a rat model of EMT in RPE cells was established via subretinal injection of dispase. Retinal function was examined by electroretinography (ERG), and retinal morphology was examined.

Results: EMT of RPE cells was effectively induced by prolonged low-density culture. After EMT occurred, only the combination of the Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor Y27632 and the TGF-β receptor inhibitor RepSox (RY treatment) effectively suppressed and reversed the EMT process, even in cells in an intermediate state of EMT. In dispase-treated Sprague-Dawley rats, RY treatment maintained the morphology of RPE cells and the retina and preserved retinal function.

Conclusions: RY treatment might promote mesenchymal-epithelial transition (MET), the inverse process of EMT, to maintain the epithelial-like morphology and function of RPE cells. This combined RY therapy could be a new strategy for treating proliferative retinal diseases, especially those involving EMT of RPE cells.
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http://dx.doi.org/10.1167/iovs.62.4.21DOI Listing
April 2021

The Combinations of Sulfur and Molybdenum Fertilization Improved Antioxidant Capacity in Grazing Nanjiang Brown Goat.

Biol Trace Elem Res 2021 Apr 14. Epub 2021 Apr 14.

School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621010, China.

To assess the impacts of sulfur (S) and molybdenum (Mo) fertilization on antioxidant capacity of grazing Nanjiang brown goat in copper (Cu)-polluted meadow, and explore the control methods of Cu pollution in natural pasture, fertilizer treatments and grazing experiments were carried out in Garzê Tibetan Autonomous Prefecture of the Western Sichuan Plateau, Sichuan Province, Southwest China. 24 hm Cu-polluted meadows were fenced and randomly divided into four groups (3 replications/group, 2 hm/replication): (1) control group, no fertilizer; (2) treatment groups, applied 1 kg Mo+40 kg S, 2 kg Mo+80 kg S, and 3 kg Mo+120 kg S per hectare for group I, group II, and group III, respectively. Seventy-two healthy Nanjiang brown goats (1 year old, 30.9 ± 1.1 kg) were randomly divided into 4 groups (3 replications/group, 6 goats/replication) and assigned to the tested pastures. The grazing experiment lasted for 60 days. The results showed that the contents of N, S, Mn, Zn, and Mo in herbage in fertilized pastures were higher than those in control group (P < 0.01). The contents of Cu and Se in herbage in fertilized pastures were lower than those in control group (P < 0.01). There were no differences among the fertilized pastures (P > 0.05). The contents of Mn, Zn, Mo, and S in serum and liver in the treatment goats were higher than those in control animals (P < 0.01). The contents of Cu and Se in serum and liver in the treatment goats were lower than those in control animals (P < 0.01). There was no difference in Fe and Co contents in herbage, serum, and liver among the four groups (P > 0.05). The levels of Hb, RBC, and PCV in blood in the treatment goats and the activities of SOD, GSH-Px, T-AOC, CAT, and Cp in serum were higher than those in control goats (P < 0.01). The contents of MDA in the treatment goats were lower than those in control animals (P < 0.01). The contents of serum Cu and Mo, and liver Cu in group III were lower than those in group I and group II (P < 0.01). Taken together, the combinations of S and Mo fertilization did not influence the mineral contents in herbage, serum, and liver, but reduced the toxicity of Cu in Cu-polluted grassland and improved antioxidant capacity in grazing Nanjiang brown goat from fertilized pastures.
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http://dx.doi.org/10.1007/s12011-021-02702-5DOI Listing
April 2021

Comparison of the antiviral effect of Arbidol and Chloroquine in treating COVID-19.

Ann Palliat Med 2021 Mar;10(3):3307-3312

Department of Respiratory and Critical Care Medicine, The 4th Hospital of Kunming City, Anning, China.

Background: The novel coronavirus disease 2019 (COVID-19) was broken out in December 2019 and soon became a global health emergency. Effective treatment for COVID-19 is urgently needed. In the present study, we aimed to evaluate the antiviral effect of Arbidol vs. Chloroquine in treating COVID-19.

Methods: We retrospectively analyzed 62 patients with COVID-19 diagnosed according to the guidelines for diagnosis and treatment of COVID-19 in China. They were divided into two groups depending on the antiviral drugs that they received. Participants in the Arbidol group (n=42) received 0.2 g Arbidol, tid for 10 days,and those in Chloroquine group (n=20) received 500 mg Chloroquine, bid for 10 days. The coronavirus negative conversion time and the length of hospital stay were analyzed and compared between the two groups.

Results: There was no significant difference in demographic and clinical characteristics between the two groups. After antiviral treatment, the nasopharyngeal specimen negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the length of hospital stay in the Arbidol group were significantly shorter than those in the Chloroquine group (18.50 vs. 25.05 days, P=0.001; 23.52 vs. 28.75 days, P=0.001). Adverse events observed during the antiviral treatment period were comparable between the two groups. Overall, 3 (7.14%) participants in the Arbidol group and 4 (20.0%) in the Chloroquine group experienced adverse events during antiviral treatment.

Conclusions: These results suggest that Arbidol is advantageous over Chloroquine in terms of the SARS-CoV-2 negative conversion and the length of hospital stay in treating COVID-19 patients.
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http://dx.doi.org/10.21037/apm-21-400DOI Listing
March 2021

Response of the critically endangered Przewalski's gazelle (Procapra przewalskii) to selenium deprived environment.

J Proteomics 2021 Apr 5:104218. Epub 2021 Apr 5.

School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, China.

Selenium (Se) is an essential mineral nutrient for animals. Se deprivation can lead to many disorders and even death. This study investigated the response of Przewalski's gazelle (P. przewalskii) to Se-deprived environment. We found that Se deprivation in soil and forage not only influenced the mineral contents of the blood and hair in P. przewalskii, but also severely disrupted their blood parameters. We identified significant changes in the abundance of 146 proteins and 25 metabolites (P < 0.05) in serum, including the selenoproteins L8IG93 (glutathione peroxidase) and F4YD09 (Cu/Zn superoxide dismutase). Furthermore, the major known proteins and metabolites associated with the Se stress response in P. przewalskii were Cu/Zn superoxide dismutase, the vitamin K-dependent protein C, the C4b-binding protein alpha chain, complement component C7, lipase linoleic acid, peptidase D, thymidine, pseudo-uridine, L-phenylalanine, L-glutamine, PGA1, and 15-deoxy-delta-12,14-PGJ2. The main signaling pathways involved included complement and coagulation cascades, metabolic pathways, and stress granule formation. Our results indicate that the intake of Se-deficient forage elicited an oxidative stress response in P. przewalskii. These findings provide insights into the response mechanisms of this threatened gazelle to Se stress, and enable the development of conservation strategies to protect populations on the Qinghai-Tibetan Plateau. SIGNIFICANCE: This study is the first to point out the presence of oxidative stress in P. przewalskii in selenium-deficient areas through proteomics and metabolomics studies. These findings should prove helpful for conservation efforts aimed at P. przewalskii populations and maintenance of the integrity of their ecological environment.
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http://dx.doi.org/10.1016/j.jprot.2021.104218DOI Listing
April 2021

Construction of a risk map to understand the vulnerability of various types of cancer patients to COVID-19 infection.

MedComm (Beijing) 2021 Mar 21;2(1):69-81. Epub 2021 Jan 21.

State Key Laboratory of Oncogenes and Related Genes Center for Single-Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine Shanghai China.

COVID-19 is leading to a global pandemic and invades human cells via . was found to be abundantly expressed in many organs and cells. However, there is no evidence about the potential risk of various types of cancer patients vulnerable to the infection of COVID-19. To obtain a risk map that indicates the novel coronavirus vulnerability of different types of cancer, we analyzed in this work the RNA sequencing datasets of cancer patients. By interrogating the datasets, we not only identified the cancer types vulnerable to COVID-19 attacks, but also we reported that variations in the mRNA expression level of correlate to various prognosis phenomenon in different types of cancer cohorts, and illustrated the underlying mechanism involved or may be related to lymphocytes infiltration. From these discoveries, we constructed an infection risk map, which indicates the vulnerability of different types of cancer to COVID-19 infection, also elucidated the correlationship between and the prognosis of cancer. We found that high expression levels lead to high risk of COVID-19 infection and poor prognosis of breast invasive carcinoma (BRCA), while better prognosis in ovarian serous cystadenocarcinoma (OV) patient cohorts. Moreover, our study demonstrated that this different pattern may correlate with the immune infiltration level.
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http://dx.doi.org/10.1002/mco2.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014155PMC
March 2021

Novel Gene Regulation in Normal and Abnormal Spermatogenesis.

Cells 2021 Mar 17;10(3). Epub 2021 Mar 17.

The NHC Key Laboratory of Male Reproduction and Genetics, Family Planning Research Institute of Guangdong Province, Guangzhou 510600, China.

Spermatogenesis is a complex and dynamic process which is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulating the normal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubular myoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.
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http://dx.doi.org/10.3390/cells10030666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002376PMC
March 2021

The Tree Shrew as a Model for Cancer Research.

Front Oncol 2021 9;11:653236. Epub 2021 Mar 9.

National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, China.

Animal disease models are necessary in medical research, and an appropriate animal model is of great importance for studies about the prevention or treatment of cancer. The most important thing in the selection of animal models is to consider the similarity between animals and humans. The tree shrew () is a squirrel-like mammal which placed in the order Scandentia. Whole-genome sequencing has revealed that tree shrews are extremely similar to primate and humans than to rodents, with many highly conserved genes, which makes the data from studies that use tree shrews as models more convincing and the research outcomes more easily translatable. In tumor research, tree shrews are often used as animal models for hepatic and mammary cancers. As research has progressed, other types of tree shrew tumor models have been developed and exhibit clinical manifestations similar to those of humans. Combining the advantages of both rodents and primates, the tree shrew is expected to be the most powerful animal model for studying tumors.
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http://dx.doi.org/10.3389/fonc.2021.653236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985444PMC
March 2021

Value of contrast-enhanced CT texture analysis in predicting IDH mutation status of intrahepatic cholangiocarcinoma.

Sci Rep 2021 Mar 25;11(1):6933. Epub 2021 Mar 25.

Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China.

To explore the value of contrast-enhanced CT texture analysis in predicting isocitrate dehydrogenase (IDH) mutation status of intrahepatic cholangiocarcinomas (ICCs). Institutional review board approved this study. Contrast-enhanced CT images of 138 ICC patients (21 with IDH mutation and 117 without IDH mutation) were retrospectively reviewed. Texture analysis was performed for each lesion and compared between ICCs with and without IDH mutation. All textural features in each phase and combinations of textural features (p < 0.05) by Mann-Whitney U tests were separately used to train multiple support vector machine (SVM) classifiers. The classification generalizability and performance were evaluated using a tenfold cross-validation scheme. Among plain, arterial phase (AP), portal venous phase (VP), equilibrium phase (EP) and Sig classifiers, VP classifier showed the highest accuracy of 0.863 (sensitivity, 0.727; specificity, 0.885), with a mean area under the receiver operating characteristic curve of 0.813 in predicting IDH mutation in validation cohort. Texture features of CT images in portal venous phase could predict IDH mutation status of ICCs with SVM classifier preoperatively.
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http://dx.doi.org/10.1038/s41598-021-86497-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994625PMC
March 2021

Zinc finger protein 91 accelerates tumour progression by activating β-catenin signalling in pancreatic cancer.

Cell Prolif 2021 Mar 23:e13031. Epub 2021 Mar 23.

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Objectives: ZFP91, an E3 ligase, has been reported to possess cancer-promoting functions. This study aimed to elucidate the exact role of ZFP91 in tumour progression of pancreatic cancer and underlying mechanisms.

Materials And Methods: We analysed the correlation between ZFP91 expression and pancreatic cancer through TCGA and GEO data sets. Growth curve, colony formation, wound healing and transwell invasion assays were conducted to evaluate proliferation, migration and invasion of lentivirus transfected pancreatic cancer cells. GSEA and Western blot analysis were performed to validate the regulatory effect of ZFP91 on β-catenin. Drug response curve and orthotopic implantation model reflected the sensitivity of chemotherapies.

Results: ZFP91 overexpression is prevalent in pancreatic cancer and negatively correlated with overall survival. ZFP91 knock-down attenuated proliferation, migration and invasion of pancreatic cancer cells. β-catenin was a downstream gene of ZFP91, and its agonist could reverse the phenotype. ZFP91 promoted EMT and chemoresistance in pancreatic cancer.

Conclusions: We demonstrated that ZFP91 promoted pancreatic cancer proliferation, migration and invasion through activating β-catenin signalling. EMT and chemoresistance were also regulated by ZFP91. ZFP91 might be a potential therapeutic target for pancreatic cancer.
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http://dx.doi.org/10.1111/cpr.13031DOI Listing
March 2021

Feasibility and Clinical Value of CT-Guided I Brachytherapy for Pain Palliation in Patients With Breast Cancer and Bone Metastases After External Beam Radiotherapy Failure.

Front Oncol 2021 5;11:627158. Epub 2021 Mar 5.

Department of Interventional Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

To evaluate the feasibility and clinical value of CT-guided iodine-125 (I) brachytherapy for pain palliation in patients with breast cancer and bone metastases after external beam radiotherapy failure. From January 2014 to July 2016, a total of 90 patients, who had received the standard therapies for bone metastases but still suffered moderate-to-severe pain, were retrospectively studied. About 42 patients were treated with both I brachytherapy and bisphosphonates (Group A), and 48 patients were treated with bisphosphonates alone (Group B). In Group A, 45 I brachytherapy procedures were performed in 42 patients with 69 bone metastases; the primary success rate of I seed implantation was 92.9%, without severe complications. Regarding pain progression of the two groups, Group A exhibited significant relief in "worst pain," "least pain," "average pain," and "present pain" 3-day after treatment and could achieve a 12-week-remission for "worst pain," "least pain," "average pain," and "present pain." The morphine-equivalent 24-h analgesic dose at 3 days, 4 weeks, 8 weeks, and 12 weeks was 91 ± 27, 53 ± 13, 31 ± 17, and 34 ± 12 mg for Group A, and 129 ± 21, 61 ± 16, 53 ± 15, and 105 ± 23 mg for Group B. Group A experienced a lower incidence of analgesic-related adverse events and better quality of life than Group B. The CT-guided I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure.
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http://dx.doi.org/10.3389/fonc.2021.627158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973096PMC
March 2021

Host-Guest Interaction-Mediated Photo/Temperature Dual-Controlled Antibacterial Surfaces.

ACS Appl Mater Interfaces 2021 Mar 18;13(12):14543-14551. Epub 2021 Mar 18.

College of Materials Science & Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Development of smart switchable surfaces to solve the inevitable bacteria attachment and colonization has attracted much attention; however, it proves very challenging to achieve on-demand regeneration for noncontaminated surfaces. We herein report a smart, host-guest interaction-mediated photo/temperature dual-controlled antibacterial surface, topologically combining stimuli-responsive polymers with nanobactericide. From the point of view of long-chain polymer design, the peculiar hydration layer generated by hydrophilic poly(2-hydroxyethyl methacrylate) (polyHEMA) segments severs the route of initial bacterial attachment and subsequent proliferation, while the synergistic effect on chain conformation transformation poly(-isopropylacrylamide) (polyNIPAM) and guest complex dissociation azobenzene/cyclodextrin (Azo/CD) complex greatly promotes the on-demand bacterial release in response to the switch of temperature and UV light. Therefore, the resulting surface exhibits triple successive antimicrobial functions simultaneously: (i) resists ∼84.9% of initial bacterial attachment, (ii) kills ∼93.2% of inevitable bacteria attack, and (iii) releases over 94.9% of killed bacteria even after three cycles. The detailed results not only present a potential and promising strategy to develop renewable antibacterial surfaces with successive antimicrobial functions but also contribute a new antimicrobial platform to biomedical or surgical applications.
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http://dx.doi.org/10.1021/acsami.0c21626DOI Listing
March 2021

Multiple Biological Activities of Maxim. Extracts and UPLC-ESI-Q-TOF/MS Characterization of Their Phytochemical Composition.

Front Pharmacol 2021 10;12:599778. Epub 2021 Feb 10.

Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China.

przewalskii Maxim. is an evergreen shrub that is used as a traditional medicine in China. However, the modern pharmacology and the chemical components of this plant has not been studied. In this paper, we aimed to investigate the antifungal, anti-inflammatory and antioxidant activities and underlying mechanism of its aqueous and ethanol extracts, and analyze their chemical composition and active compounds of . The antifungal activity was determined , and anti-inflammatory and antioxidant activities and underlying mechanism of its aqueous and ethanol extracts were evaluated and in RAW 264.7 cells. The chemical composition were analyzed using UPLC-ESI-Q-TOF/MS, and the contents of six compounds were determined via HPLC. Both extracts of showed promising anti-inflammatory activity ; decreased the production of four inflammatory cytokines, namely, nitric oxide, IL-1β, IL-6 and TNF-, in RAW 264.7 cells induced by lipopolysaccharide; and exhibited weak cytotoxicity. The extracts significantly scavenged DPPH radicals, superoxide radicals and hydroxyl radicals to exert antioxidant effects . The two extracts also exhibited cellular antioxidant activity by increasing superoxide dismutase and CAT activities and decreasing malondialdehyde content in RAW 264.7 cells induced by LPS. However, the antifungal activity of the two extracts was weak. Nine flavonoids were identified by UPLC-ESI-Q-TOF/MS. Of these, six compounds were analyzed quantitatively, including avicularin, quercetin, azaleatin, astragalin and kaempferol, and five compounds (myricetin 3-O-galactoside, paeoniflorin, astragalin, azaleatin and kaempferol) were found in this species for the first time. These compounds demonstrated antioxidant activities that were similar to those of the extracts and were thought to be the active compounds in the extracts extracts presented promising anti-inflammatory and antioxidant activities. The extracts contained amounts of valuable flavonoids (8.98 mg/g fresh material) that were likely the active compounds in the extract contributing to the potential antioxidant activity. These results highlight the potential of as a source of natural antioxidant and anti-inflammatory agents for the pharmaceutical industry.
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http://dx.doi.org/10.3389/fphar.2021.599778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957927PMC
February 2021

Ultrasound-Guided Pudendal Nerve Block Combined with Propofol Deep Sedation versus Spinal Anesthesia for Hemorrhoidectomy: A Prospective Randomized Study.

Pain Res Manag 2021 26;2021:6644262. Epub 2021 Feb 26.

Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, China.

Several anesthesia techniques were applied to hemorrhoidectomy, but postoperative pain and urinary retention were still two unsolved problems. The aim of this prospective randomized study was to evaluate the effect of ultrasound-guided pudendal nerve block (PNB) combined with deep sedation compared to spinal anesthesia for hemorrhoidectomy. . One hundred and twenty patients undergoing Milligan-Morgan hemorrhoidectomy were randomized to receive PNB combined with deep sedation using propofol (Group PNB,  = 60) or spinal anesthesia (Group SA,  = 60). Pain intensity was assessed using the visual analogue scale (0: no pain to 10: worst possible pain). The primary outcome was pain scores recorded at rest at 3, 6, 12, 24, 36, and 48 h and on walking at 12, 24, 36, and 48 h postoperatively. Secondary outcomes were analgesic consumption, side effects, and patient satisfaction after surgery. . Ultrasound-guided bilateral PNB combined with deep sedation using propofol could successfully be applied to Milligan-Morgan hemorrhoidectomy. Postoperative pain intensity was significantly lower in Group PNB compared to Group SA at rest at 3, 6, 12, 24, 36, and 48 h ( < 0.001) and during mobilization at 12, 24, 36, and 48 h ( < 0.001) postoperatively. Sufentanil consumption in Group PNB was significantly lower than that in Group SA, during 0-24 h ( < 0.001) and during 24-48 h ( < 0.001) postoperatively. Urinary retention was significantly lower in Group PNB compared to Group SA (6.9% vs 20%, =0.034). The patients in Group PNB had higher satisfaction compared to Group SA ( < 0.001). . Ultrasound-guided PNB combined with propofol sedation is an effective anesthesia technique for Milligan-Morgan hemorrhoidectomy.
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http://dx.doi.org/10.1155/2021/6644262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935604PMC
February 2021

Overexpression of long non-coding RNA XIST promotes IL-1β-induced degeneration of nucleus pulposus cells through targeting miR-499a-5p.

Mol Cell Probes 2021 Mar 17;57:101711. Epub 2021 Mar 17.

Department of Orthopedics, Zhejiang Hospital, Xihu District, Hangzhou City, Zhejiang Province, 310030, China. Electronic address:

Background: Long non-coding RNA X-interactive specific transcript (XIST) is implicated in many diseases. However, its role and interaction with microRNA (miR)-499a-5p in intervertebral disc degeneration (IDD) remained unclear.

Methods: Nucleus pulposus (NP) tissue samples were collected and nucleus pulposus cells (NPCs) were isolated for Interleukin-1β (IL-1β) treatment and identification. XIST and miR-499a-5p expressions in the tissue were measured with quantitative real-time polymerase chain reaction (qRT-PCR). After IL-1β treatment, NPC apoptosis was detected by flow cytometry. The potential binding sites of XIST and miR-499a-5p were predicted by starBase and confirmed by dual-luciferase reporter assay. Relative expressions of tissue inhibitor of metalloproteinases-3 (TIMP-3), Matrix metalloproteinases-3 (MMP-3), MMP-13, Collagen II, Aggrecan and apoptosis-related proteins (Bcl-2 associated X protein, Bax; B-cell lymphoma 2, Bcl-2; cleaved caspase-3) were measured by qRT-PCR and Western blot as needed.

Results: XIST expression was upregulated in the NP tissues of patients with IDD, and IL-1β treatment resulted in a degradation of NPCs. Overexpressed XIST promoted the effects of IL-1β on increasing NPC apoptosis and expressions of XIST, MMP-3, MMP-13, Bax and Cleaved caspase-3, but down-regulated TIMP-3, Collagen II, Aggrecan and Bcl-2 expressions. Silencing XIST, however, showed the opposite effects to its overexpression. MiR-499a-5p expression was downregulated in NP tissues of IDD patients and could bind with XIST, while its upregulation reversed the effects of overexpressed XIST in the IL-1β-treated NPCs.

Conclusion: Overexpressed XIST caused NPC degeneration through promoting apoptosis and extracellular matrix degradation of IL-1β-treated NPCs through targeting miR-499a-5p, and therefore can serve as a potential treatment for IDD.
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http://dx.doi.org/10.1016/j.mcp.2021.101711DOI Listing
March 2021

Intraoperative Assessment and Photothermal Ablation of the Tumor Margins Using Gold Nanoparticles.

Adv Sci (Weinh) 2021 Mar 18;8(5):2002788. Epub 2021 Jan 18.

The Fourth Affiliated Hospital Zhejiang University School of Medicine Yiwu 322000 P. R. China.

Surgical resection is commonly used for therapeutic management of different solid tumors and is regarded as a primary standard of care procedure, but precise localization of tumor margins is a major intraoperative challenge. Herein, a generalized method by optimizing gold nanoparticles for intraoperative detection and photothermal ablation of tumor margins is introduced. These nanoparticles are detectable by highly sensitive surface-enhanced Raman scattering imaging. This non-invasive technique assists in delineating the two surgically challenged tumors in live mice with orthotopic colon or ovarian tumors. Any remaining residual tumors are also ablated by using post-surgical adjuvant photothermaltherapy (aPTT), which results in microscale heat generation due to interaction of these nanoparticles with near-infrared laser. Ablation of these post-operative residual micro-tumors prolongs the survival of mice significantly and delays tumor recurrence by 15 days. To validate clinical translatability of this method, the pharmacokinetics, biodistribution, Raman contrast, aPTT efficiency, and toxicity of these nanoparticles are also investigated. The nanoparticles have long blood circulation time (≈24 h), high tumor accumulation (4.87 ± 1.73%ID g) and no toxicity. This high-resolution and sensitive intraoperative approach is versatile and can be potentially used for targeted ablation of residual tumor after resection within different organs.
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http://dx.doi.org/10.1002/advs.202002788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927626PMC
March 2021

Development and validation of a CT-based radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma.

Chin J Cancer Res 2021 Feb;33(1):69-78

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Objectives: To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma (GA).

Methods: This retrospective study enrolled 592 patients with clinicopathologically confirmed GA (low-grade: n=154; high-grade: n=438) from January 2008 to March 2018 who were divided into training (n=450) and validation (n=142) sets according to the time of computed tomography (CT) examination. Radiomic features were extracted from the portal venous phase CT images. The Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection, data dimension reduction and radiomics signature construction. Multivariable logistic regression analysis was applied to develop the prediction model. The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram. The performance of the nomogram was assessed with respect to its calibration and discrimination.

Results: A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA (P<0.001 for both training and validation sets). A nomogram including the radiomics signature and tumor location as predictors was developed. The model showed both good calibration and good discrimination, in which C-index in the training set, 0.752 [95% confidence interval (95% CI): 0.701-0.803]; C-index in the validation set, 0.793 (95% CI: 0.711-0.874).

Conclusions: This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures, which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.01.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941693PMC
February 2021

The complete chloroplast genome of a distinctive meadow-rue, (Ranunculaceae).

Mitochondrial DNA B Resour 2021 Feb 8;6(2):404-405. Epub 2021 Feb 8.

School of Ecology and Nature Conservation, Beijing Forestry University, 35 East Qinghua Rd., Haidian District, Beijing, PR China.

is a morphologically distinctive species in the genus with very reduced filiform compound leaves and big pinkish flowers occurring in dry slopes of northern China. Herein, we report the first complete chloroplast genome sequence of . The chloroplast genome sequence was 155,923 bp in length, with large and small single-copy regions (LSC with 85,323 bp and SSC with 17,628 bp in length) separated by two inverted repeat regions (IRs with 26,486 bp). The total GC content was 38.3%. The complete plastome sequence contained 111 genes, including 77 protein-coding, 30 , and four genes. The phylogenetic analysis of based on the complete chloroplast genomes available online was also presented in this study.
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http://dx.doi.org/10.1080/23802359.2020.1870880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872574PMC
February 2021

Bioinspired protein corona strategy enhanced biocompatibility of Ag-Hybrid hollow Au nanoshells for surface-enhanced Raman scattering imaging and on-demand activation tumor-phototherapy.

Biomaterials 2021 Apr 20;271:120734. Epub 2021 Feb 20.

Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China; Institute of Translational Medicine, Zhejiang University, Hangzhou, 310009, China; State Key Laboratory of Modern Optical Instrumentations, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Silver-based hybrid nanoprobes for surface-enhanced Raman scattering (SERS) imaging show their tremendous potential for precise biological detection and mediated phototherapy. However, the severe toxicity induced by Ag to normal mammalian cells hinders its further application. Herein, we presented a versatile bioinspired protein corona strategy through assembling bovine serum albumin (BSA) protected Raman tag DTTC-conjugated Ag-hybrid hollow Au nanoshells (hollow AgAu-DTTC-BSA), which their silver ion release and reactive oxygen species (ROS) generation are significantly suppressed, enabling no damage to normal cells and tissues, but can be reactivated on-demand under laser-irradiation at the tumor site. These nanoshells could also produce strong localized surface plasmon resonance for efficient-stable photothermal effect and enhanced SERS activity under laser irradiation, approved by both theoretical and experimental calculations. Furthermore, the biocompatible hollow AgAu-DTTC-BSA could detect both primary tumor tissues and tiny liver metastases (~0.18 mm) in orthotopic/subcutaneous CT26 colon tumor-bearing mice models. We also demonstrate their excellent therapeutic efficacy for colorectal solid neoplasms by accurate SERS imaging-guided photothermal therapy, simultaneously assisted with toxic Ag ion and ROS. These results suggest that hollow AgAu-DTTC-BSA is promising imaging assisted photothermal agents for solid tumor theranostics and enhancing the potential of Ag-based nanoparticles for practical treatment.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120734DOI Listing
April 2021

Antiviral Bafilomycins from a Feces-Inhabiting sp.

J Nat Prod 2021 02 8;84(2):537-543. Epub 2021 Feb 8.

Group of Peptides and Natural Products Research, School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, People's Republic of China.

A new bafilomycin derivative () and another seven known bafilomycins (-) were isolated from feces-derived sp. HTL16. The structure of was elucidated by 1D and 2D NMR spectroscopic analysis. Biological testing demonstrated that these bafilomycins exhibited potent antiviral activities against the influenza A and SARS-CoV-2 viruses, with IC values in the nanomolar range, by inhibiting the activity of endosomal ATP-driven proton pumps.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01243DOI Listing
February 2021

The Prognostic Value of Myocardial Injury in COVID-19 Patients and Associated Characteristics.

Res Sq 2021 Feb 19. Epub 2021 Feb 19.

Since December 2019, Coronavirus disease 2019 (COVID-19) has emerged as an international pandemic. COVID-19 patients with myocardial injury might need special attention. However, understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID-19 patients. This retrospective, single-center study finally included 304 hospitalized COVID-19 cases confirmed by real-time RT-PCR from January 11 to March 25, 2020. Myocardial injury was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19 associated mortality. Of 304 COVID-19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID-19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C-reactive protein (CRP, median, 84.9 vs 28.5 mg/L, p<0.001), procalcitonin levels (median, 0.29 vs 0.06 ng/ml, p<0.001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio, HR=7.02, 95% confidence interval, CI, 4.45-11.08, p<0.001) than those without myocardial injury. Myocardial injury (HR=4.55, 95% CI, 2.49-8.31, p<0.001), senior age, CRP levels, and novel coronavirus pneumonia (NCP) types on admission were independent predictors to mortality in COVID-19 patients. COVID patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury and higher HsTNI are both strongest independent predictors to COVID related mortality after adjusting confounding factors. In addition, senior age, CRP levels and NCP types are also associated with mortality. Not applicable.
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http://dx.doi.org/10.21203/rs.3.rs-251810/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899459PMC
February 2021

Studying Scale Dependency of Aerosol Cloud Interactions using Multi-Scale Cloud Formulations.

Mon Weather Rev 2020 Nov;77(11):3847-3868

Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.

The WRF-ACI model configuration is used to investigate the scale dependency of aerosol-cloud interactions (ACI) across the "grey zone" scales for grid and subgrid-scale clouds. The impacts of ACI on weather are examined across regions in the eastern and western U. S. at 36, 12, 4, and 1 km grid spacing for short-term periods during the summer of 2006. ACI impacts are determined by comparing simulations with current climatological aerosol levels to simulations with aerosol levels reduced by 90%. The aerosol-cloud lifetime effect is found to be the dominant process leading to suppressed precipitation in regions of the eastern U.S., while regions in the western U. S. experience offsetting impacts on precipitation from the cloud lifetime effect and other effects that enhance precipitation. Generally, the cloud lifetime effect weakens with decreasing grid spacing due to a decrease in relative importance of autoconversion compared to accretion. Subgrid-scale ACI are dominant at 36 km, while grid-scale ACI are dominant at 4 and 1 km. At 12 km grid spacing, grid-scale and subgrid-scale ACI processes are comparable in magnitude and spatial coverage, but random perturbations in grid-scale-ACI impacts make the overall grid-scale-ACI impact appear muted. This competing behavior of grid and subgrid-scale clouds complicate the understanding of ACI at 12 km within the current WRF modeling framework. The work implies including subgrid-scale-cloud microphysics and ice/mixed phase cloud ACI processes may be necessary in weather and climate models to study ACI effectively.
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http://dx.doi.org/10.1175/JAS-D-19-0203.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886284PMC
November 2020

Prognostic Value of the Albumin-to-Alkaline Phosphatase Ratio before Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma.

Chemotherapy 2021 Feb 18:1-7. Epub 2021 Feb 18.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Introduction: The aim of this study was to evaluate the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) in patients with nonmetastatic nasopharyngeal carcinoma (NPC).

Methods: Patients with nonmetastatic NPC who underwent chemoradiotherapy (CRT) were retrospectively analyzed. The AAPR was calculated using the last value of albumin to alkaline phosphatase that was measured within 1 week before CRT. The optimal cutoff value for the AAPR value was determined by an X-tile plot. Propensity score matching (PSM) was performed to balance the differences of the baseline characteristics. The Kaplan-Meier method and log-rank test were used to calculate the survival. A Cox proportional hazards regression model was conducted for the multivariate analysis.

Results: Totally, 87 patients with nonmetastatic NPC who underwent CRT were included in the analysis. The optimal cutoff level for the AAPR was 0.46. The group with an AAPR ≤0.46 was more likely to have poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (p = 0.023, p = 0.031 and p = 0.027, for OS, PFS, and DMFS, respectively). In Cox proportional hazards analysis, high AAPR was a better prognostic predictor.

Conclusion: AAPR may be a reliable prognostic index for nonmetastatic NPC patients.
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http://dx.doi.org/10.1159/000513058DOI Listing
February 2021

Modification of oncolytic adenovirus and its application in cancer therapy.

Discov Med 2020 Nov-Dec;30(161):129-144

National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.

Oncolytic virus refers to a type of virus that can replicate in tumor cells and eventually lyse them. Oncolytic adenoviruses are widely used because of their acceptable safety, but they are also limited in their clinical applications due to their own limitations. Therefore, the adenovirus is modified in multiple ways to improve the safety of the treatment, enhance the impact of oncolysis, and reduce the effect of neutralizing antibodies on the virus. The combined application of oncolytic adenovirus and other drugs plays a synergistic role in the treatment of tumors.
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February 2021

Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy for advanced biliary tract cancers with biliary obstruction: a multicentre, retrospective, controlled study.

Eur Radiol 2021 Feb 13. Epub 2021 Feb 13.

Department of Interventional Therapy, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, 106 Zhongshan Second Road, Guangzhou, 510080, Guangdong, China.

Objective: To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO).

Methods: We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed.

Results: Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1-9.3) than in the control group (4.3 months, 95% CI: 3.6-5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1-16.5; control: 8.5 months, 95% CI: 7.6-9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs.

Conclusions: Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO.

Key Points: • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.
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http://dx.doi.org/10.1007/s00330-021-07716-0DOI Listing
February 2021

Meta-analysis of the impact of role stress on the turnover intention of medical staff in tertiary hospitals.

Ann Palliat Med 2021 Jan;10(1):469-478

The Party and Government Office, The Affiliated Hospital of North Sichuan Medical College, Nanchong, China. Email:

Background: This study aimed to conduct a meta-analysis on the effect of role stress on the turnover intention of medical staff in tertiary hospitals.

Methods: Based on the inclusion and exclusion criteria of literatures, we searched the English language databases Science Direct, PubMed, Springerlink, CBM, ISI, and Web of Science for studies published between January 2000 and October 2020 on the effect of role stress on the turnover intention of medical staff in tertiary hospitals. Publications were strictly screened according to the standards, and RevMan5.3 was adopted to conduct a meta-analysis of the relevant data. The influence of role stress and its various dimensions, such as role conflict, role ambiguity, and role overload on medical staff in tertiary hospitals turnover intention was analyzed. The Q test was adopted for heterogeneity analysis and the Egger's test adopted to detect publication bias.

Results: A total of 12 publications meeting the requirements were included in this study. The results showed that the combined correlation coefficient r between total role stress and turnover intention was 0.2503 (95% CI: 0.2235‒0.3489). There was also a positive correlation between role stress and the turnover intention of medical staff in tertiary hospitals (r=0.2503). The meta-analysis results of each dimension of role stress showed turnover intention was positively correlated with role conflict (r=0.2838), role ambiguity (r=0.2628), and role overload (r=0.2687).

Conclusions: The greater the role stress of medical staff in tertiary hospitals, the stronger the turnover intention. Measures must be taken to avoid the loss of medical staff and improve the quality of medical services.
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http://dx.doi.org/10.21037/apm-20-2446DOI Listing
January 2021

T1rho shortening effect of fat in liver steatosis after fat suppression: approximate estimation in a methionine and choline-deficient (MCD) diet rat model.

Quant Imaging Med Surg 2021 Feb;11(2):870-875

Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

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http://dx.doi.org/10.21037/qims-20-1253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779932PMC
February 2021

Inter-observer agreement of computed tomography and magnetic resonance imaging on gross tumor volume delineation of intrahepatic cholangiocarcinoma: an initial study.

Quant Imaging Med Surg 2021 Feb;11(2):579-585

Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor, and local radiotherapy has a positive effect on patients with an unresectable tumor. Accurate delineation of gross tumor volume (GTV) is crucial to improve the efficacy of radiotherapy. The purpose of this article was to evaluate the consistency of CT, diffusion weighted imaging (DWI) and Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced MRI on GTV delineation of ICC.

Methods: Fourteen patients with ICC underwent CT (Plain and Portal, CT scans before and 70 s after the injection of Omnipaque, respectively), DWI, and Gd-EOB-DTPA-enhanced MRI (EOB 70 s and EOB 15 min, mDIXON scans at 70 s and 15 min after the injection of Gd-EOB-DTPA, respectively) examinations before radiotherapy. Volumes of GTV delineation on CT and MRI images were recorded. Dice similarity coefficient (DSC) was calculated to evaluate the spatial overlap.

Results: Tumor volume on DWI and EOB 15 min were larger than that on EOB 70 s significantly (both P=0.004). DSC of DWI was significantly larger than that of other CT and MRI sequences (all P≤0.002). DSC of EOB 15 min tended to be larger than that of other CT sequences and EOB 70 s, however, without significances (all P>0.005). Significant correlation was found between DSC and tumor volume (R=0.35, P=0.003).

Conclusions: DWI had significantly higher agreement on GTV delineation of ICC. GTV delineations of ICC on Gd-EOB-DTPA-enhanced MRI showed excellent inter-observer agreement. Fusion of CT and MRI images should be considered to improve the accuracy of GTV delineation.
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http://dx.doi.org/10.21037/qims-19-1093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779918PMC
February 2021

Clonal evolution in liver cancer at single-cell and single-variant resolution.

J Hematol Oncol 2021 Feb 2;14(1):22. Epub 2021 Feb 2.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.
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http://dx.doi.org/10.1186/s13045-021-01036-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852352PMC
February 2021

Development and application of reverse genetic technology for the influenza virus.

Virus Genes 2021 Apr 2;57(2):151-163. Epub 2021 Feb 2.

National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, 530021, Guangxi, China.

Influenza virus is a common virus in people's daily lives, and it has certain infectivity in humans and animals. Influenza viruses have the characteristics of a high mutation rate and wide distribution. Reverse genetic technology is primarily used to modify viruses at the DNA level through targeted modification of the virus cDNA. Genetically modified influenza viruses have a unique advantage when researching the transmission and pathogenicity of influenza. With the continuous development of oncolytic viruses in recent years, studies have found that influenza viruses also have certain oncolytic activity. Influenza viruses can specifically recognize tumor cells; activate cytotoxic T cells, NK cells, dendritic cells, etc.; and stimulate the body to produce an immune response, thereby killing tumor cells. This article will review the development and application of influenza virus reverse genetic technology.
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http://dx.doi.org/10.1007/s11262-020-01822-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851324PMC
April 2021