Publications by authors named "Song Xu"

497 Publications

Growth of ZnInS on MOF-Derived Ni-Fe LDH to Construct Ternary-Shelled Nanotubes for Efficient Photocatalytic Hydrogen Evolution.

Inorg Chem 2021 Jun 22. Epub 2021 Jun 22.

Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, Changzhou University, Changzhou 213164, P. R. China.

A rational design of a novel ternary-shelled nanotube is attractive in photocatalytic water splitting. Herein, ZnInS nanosheets were grown on the surface of MIL-88A-derived Ni-Fe layered double hydroxide (LDH) to fabricate ternary-shelled nanotubes ([email protected] LDH) a self-assembly strategy. Characterization indicates that the [email protected] LDH heterostructure exhibits a high surface area and a well-defined ternary-shelled hollow structure. The optimal heterostructure presents a remarkably improved photocatalytic hydrogen production rate (2035.81 μmol g h) compared with bare ZnInS and MIL-88A-derived Ni-Fe LDH under visible light illumination. The effect of ZnInS loading on the photocatalytic performance and stability of [email protected] LDH is systematically studied. The [email protected] LDH heterostructure can make better use of the inner space, provide abundant reactive sites, improve light harvesting, accelerate interfacial electron transfer, and further promote photocatalytic hydrogen evolution. Based on the electrocatalytic performance, the probable photocatalytic mechanism and the electron transfer pathway can be proposed. Our work provides a facile and efficient strategy to construct ternary-shelled heterojunction photocatalysts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.1c01064DOI Listing
June 2021

Rictor is a novel regulator of TRAF6/TRAF3 in osteoclasts.

J Bone Miner Res 2021 Jun 22. Epub 2021 Jun 22.

Department of Cell Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Southern Medical University, Guangzhou, 510515, China.

Tumor necrosis factor receptor-associated factors (TRAFs) are crucial for receptor activator of nuclear factor-κB (RANK) activation in osteoclasts. However, the upstream mechanisms of TRAF members in the osteoclastic lineage remain largely unknown. Here, we demonstrated that Rictor, a key component of mechanistic target of rapamycin complex 2 (mTORC2), was crucial for TRAF6/TRAF3 expression in osteoclasts. Our ex vivo and in vivo studies showed that Rictor ablation from the osteoclastic lineage reduced osteoclast numbers and increased bone mass in mice. Mechanistically, we found that Rictor ablation restricted osteoclast formation which disrupted TRAF6 stability and caused autophagy block in a manner distinct from mTORC1, resulting in reduced TRAF3 degradation. Boosting TRAF6 expression or knockdown of TRAF3 levels in Rictor-deficient cells could both overcome the defect. Moreover, Rictor could interact with TRAF6 upon RANKL stimulation and loss of Rictor impaired TRAF6 stability and promoted its ubiquitinated degradation. These findings established an innovative link between Rictor, TRAF protein levels and autophagic block. More importantly, mTOR complexes in the osteoclastic lineage are likely switches for coordinating TRAF6 and TRAF3 protein levels, and Rictor may function as an essential upstream regulator of TRAF6/TRAF3 that is partially independent of mTORC1 activity. Inhibitors targeting Rictor may therefore be valuable for preventing or treating osteoclast-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4398DOI Listing
June 2021

Comparison of lateral entry and crossed entry pinning for pediatric supracondylar humeral fractures: a meta-analysis of randomized controlled trials.

J Orthop Surg Res 2021 Jun 9;16(1):366. Epub 2021 Jun 9.

Department of Orthopedics, Ningbo No. 6 Hospital, 1059 Zhongsandong Road, Ningbo, Zhejiang, 315040, People's Republic of China.

Background: Closed reduction and pinning entry fixation have been proposed as treatment strategies for displaced supracondylar humeral fractures (SCHFs) in children. However, controversy exists regarding the selection of the appropriate procedure. Hence, this meta-analysis was conducted to compare the effect of lateral and crossed pin fixation for pediatric SCHFs, providing a reference for clinical treatment.

Methods: Online databases were systematically searched for randomized controlled trials (RCTs) comparing lateral pinning entry and crossed pinning entry for children with SCHFs. The primary endpoints were iatrogenic ulnar nerve injuries, complications, and radiographic and functional outcomes.

Results: Our results showed that iatrogenic ulnar nerve injuries occurred more commonly in the crossed pinning entry group than in the lateral pinning entry group (RR = 4.41, 95% CI 1.97-9.86, P < 0.05). However, its risk between the crossed pinning with mini-open incisions group and the lateral pinning entry group was not significantly different (RR = 1.58, 95% CI 0.008-29.57, P = 0.76). The loss of reduction risk was higher in the lateral pinning entry group than in the crossed pinning entry group (RR = 0.66; 95% CI 0.49-0.89, P < 0.05). There were no significant differences in the carry angle, Baumann angle, Flynn scores, infections, and other complications between these two groups.

Conclusions: The crossed pinning entry with mini-open incision technique reduced the loss of reduction risk, and the risk of iatrogenic ulnar nerve injury was lower than in the lateral pinning entry group. The crossed pinning entry with mini-open incision technique is an effective therapeutic strategy for managing displaced supracondylar humeral fractures in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-021-02505-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188794PMC
June 2021

Bacillus amyloliquefaciens FH-1 significantly affects cucumber seedlings and the rhizosphere bacterial community but not soil.

Sci Rep 2021 Jun 8;11(1):12055. Epub 2021 Jun 8.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, People's Republic of China.

Plant growth-promoting bacteria (PGPB) inoculants have been applied worldwide. However, the ecological roles of PGPB under different soil conditions are still not well understood. The present study aimed to explore the ecological roles of Bacillus amyloliquefaciens FH-1 (FH) on cucumber seedlings, rhizosphere soil properties, and the bacterial community in pot experiments. The results showed that FH had significant effects on cucumber seedlings and the rhizosphere bacterial community but not on soil properties. The FH promoted cucumber seedlings growth, reduced the rhizosphere bacterial diversity, increased Proteobacteria, and decreased Acidobacteria. Linear discriminant analysis (LDA) effect size (LEfSe) revealed that FH enriched two taxa (GKS2_174 and Nannocystaceae) and inhibited 18 taxa (mainly Acidobacteria, Actinobacteria, BRC1, Chloroflexi, Plantctomycetes, and Verrucomicrobia). Co-occurrence network analysis demonstrated that FH increased bacteria-bacteria interactions and that Bacillus (genus of FH) had few interactions with the enriched and inhibited taxa. This might indicate that FH does not directly affect the enriched and inhibited taxa. Correlation analysis results displayed that cucumber seedlings' weight and height/length (except root length) were significantly correlated with the 18 inhibited taxa and the enriched taxa Nannocystaceae. It was speculated that FH might promote cucumber seedling growth by indirectly enriching Nannocystaceae and inhibiting some taxa from Acidobacteria, Actinobacteria, BRC1, Chloroflexi, Plantctomycetes, and Verrucomicrobia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91399-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187646PMC
June 2021

Chlorogenic Acid Sustained-release Gel for Treatment of Glioma and Hepatocellular Carcinoma.

Eur J Pharm Biopharm 2021 Jun 4. Epub 2021 Jun 4.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, China. Electronic address:

Chlorogenic acid (CGA) may provide an effective and safe option for tumor treatment. However, its application is limited because of short residence time in vivo and repeated administration required. A phospholipid-based in situ gel containing chlorogenic acid (CGA PG) was prepared via a simple way. The CGA PG exhibited good fluidity, easy injectability, high-drug-loading capacity, and suitable sustained-release behavior whether in vitro or in vivo. Furthermore, CGA PG could suppress tumor growth with no significant side effects. Overall, CGA PG may be a promising sustained drug delivery system with excellent therapeutic effect on glioma and hepatocellular carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpb.2021.05.028DOI Listing
June 2021

The synthesis review of the approved tyrosine kinase inhibitors for anticancer therapy in 2015-2020.

Bioorg Chem 2021 Aug 24;113:105011. Epub 2021 May 24.

Natural Medicine Research Center, College of veterinary medicine, Sichuan Agricultural University, Chengdu 611130, PR China.

In the 21st century, cancer is the major public health problem worldwide. Based on the important roles of protein tyrosine kinase, the accelerated hunt for potent small-molecule tyrosine kinase inhibitors has led to the success of 30 newly inhibitors in this family for the cancer therapy in last five years. In this review, we updated their synthesis methods, and compared the original research routes with the optimized routes for each PTK inhibitor against different target, in order to make an outlook on the future synthesis of potential PTK inhibitors for anticancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.105011DOI Listing
August 2021

MiR-146a Negatively Regulates Aspergillus fumigatus-Induced TNF-α and IL-6 Secretion in THP-1 Macrophages.

Mycopathologia 2021 Jun 4. Epub 2021 Jun 4.

Jiangsu Key Laboratory of Molecular Biology for Skin, Institute of Dermatology, Diseases and STIs, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210042, People's Republic of China.

Aspergillus fumigatu (A. fumigatus) is one of the most common important fungal pathogens that cause life-threatening infectious disease in immunocompromised individuals. However, the host immune response against this pathogenic mold is not fully understood. MicroRNAs (miRNAs) play essential roles in regulating innate immunity. Thus, we investigated the function of miR-146a in inflammatory responses in macrophages after A. fumigatus stimulation in this study. We found that TNF-α and IL-6 were increased in THP-1 macrophage-like cells treated with A. fumigatus at both the mRNA and protein levels. The interaction between THP-1 macrophage-like cells and A. fumigatus resulted in a long-lasting increase in miR-146a expression dependent on p38 MAPK and NF-κB signaling. In A. fumigatus-challenged THP-1 macrophage-like cells, overexpression of miR-146a by miR-146a mimics decreased TNF-α and IL-6 production, whereas downregulation of miR-146a by anti-miR-146a significantly enhanced the level of TNF-α and IL-6. Our study demonstrates that the crosstalk between miR-146a and the inflammation-regulating p38 MAPK and NF-κB pathways might be a fine-tuning mechanism in the modulation of the inflammatory response in macrophages infected with A. fumigatus. Our findings illuminate the crucial role of miR-146a in the pathogenesis of human diseases associated with A. fumigatus infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11046-021-00538-0DOI Listing
June 2021

Effect of liquid volume and microflora source on degradation rate and microbial community in corn stover degradation.

AMB Express 2021 Jun 1;11(1):80. Epub 2021 Jun 1.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, No. 32, West 7th Avenue, Tianjin Airport Economic Area, Tianjin, 300308, P R China.

Degradation is the bottleneck in the utilization of crop straw. In this paper, we screened the microbial consortia degrading corn stover from straw degrading consortia MC1 (M), sheep feces (Y), and mixtures (Q) of M, Y, and cattle feces. The effects of microflora source and liquid volume (representing dissolved oxygen) on the microbial community and degradation rate of corn stover were investigated. The results showed that the degradation rate and cellulase activity of a 200 mL liquid volume (L2) were significantly higher than that of 100 mL (L1). Microflora source had a significant effect on bacterial and fungal diversity, composition and taxa. Q and Y had higher bacterial and fungal α-diversity than that of M. The degradation rate was significantly correlated with cellulase activity but not with microbial diversity. This indicated that liquid volume had a significant effect on degradation rate while microflora source had a significant effect on microbial community in corn stover degradation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13568-021-01233-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169732PMC
June 2021

Delivery of siHIF-1α to Reconstruct Tumor Normoxic Microenvironment for Effective Chemotherapeutic and Photodynamic Anticancer Treatments.

Small 2021 May 25:e2100609. Epub 2021 May 25.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, P. R. China.

The tumor hypoxic microenvironment not only induces genetic and epigenetic changes in tumor cells, immature vessels formation for oxygen demand, but also compromises the efficiency of therapeutic interventions. On the other hand, conventional therapeutic approaches which kill tumor cells or destroy tumor blood vessels to block nutrition and oxygen supply usually facilitate even harsher microenvironment. Thus, simultaneously relieving the strained response of tumor cells and blood vessels represents a promising strategy to reverse the adverse tumor hypoxic microenvironment. In the present study, an integrated amphiphilic system (RSCD) is designed based on Angiotensin II receptor blocker candesartan for siRNA delivery against the hypoxia-inducible factor-1 alpha (HIF-1α), aiming at both vascular and cellular "relaxation" to reconstruct a tumor normoxic microenvironment. Both in vitro and in vivo studies have confirmed that the hypoxia-inducible HIF-1α expression is down-regulated by 70% and vascular growth is inhibited by 60%. The "relaxation" therapy enables neovascularization with more complete and organized structures to obviously increase the oxygen level inside tumor, which results in a 50% growth inhibition. Moreover, reconstruction of tumor microenvironment enhances tumor-targeted drug delivery, and significantly improves the chemotherapeutic and photodynamic anticancer treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/smll.202100609DOI Listing
May 2021

Comparison of Lobectomy and Sublobar Resection for Stage IA Elderly NSCLC Patients (≥70 Years): A Population-Based Propensity Score Matching's Study.

Front Oncol 2021 7;11:610638. Epub 2021 May 7.

Department of Lung Cancer Surgery, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.

Background: To investigate the differences in survival between lobectomy and sub-lobar resection for elderly stage I non-small-cell lung cancer (NSCLC) patients using the Surveillance, Epidemiology, and End Results (SEER) registry.

Method: The data of stage IA elderly NSCLC patients (≥ 70 years) with tumors less than or equal to 3 cm in diameter were extracted. Propensity-matched analysis was used. Lung cancer-specific survival (LCSS) was compared among the patients after lobectomy and sub-lobar resection. The proportional hazards model was applied to identify multiple prognostic factors.

Results: A total of 3,504 patients met criteria after propensity score matching (PSM). Although the LCSS was better for lobectomy than for sub-lobar resection in patients with tumors ≤ 3 cm before PSM (p < 0.001), no significant difference in the LCSS was identified between the two treatment groups after PSM (p = 0.191). Multivariate Cox regression showed the elder age, male gender, squamous cell carcinoma (SQC) histology type, poor/undifferentiated grade and a large tumor size were associated with poor LCSS. The subgroup analysis of tumor sizes, histologic types and lymph nodes (LNs) dissection, there were also no significant difference for LCSS between lobectomy and sub-lobar resection. The sub-lobar resection was further divided into segmentectomy or wedge resection, and it demonstrated that no significant differences in LCSS were identified among the treatment subgroups either. Multivariate Cox regression analysis showed that the elder age, poor/undifferentiated grade and a large tumor size were a statistically significant independent factor associated with survival.

Conclusion: In terms of LCSS, lobectomy has no significant advantage over sub-lobar resection in elderly patients with stage IA NSCLC if lymph node assessment is performed adequately. The present data may contribute to develop a more suitable surgical treatment strategy for the stage IA elderly NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.610638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139614PMC
May 2021

MiR-454-3p Promotes Oxaliplatin Resistance by Targeting PTEN in Colorectal Cancer.

Front Oncol 2021 4;11:638537. Epub 2021 May 4.

Department of Oncology, Zhangjiagang First People's Hospital, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.

Colorectal cancer is one of the most common malignancies worldwide. Oxaliplatin is the first-line chemotherapeutic agent for the treatment of advanced colorectal cancer. However, acquired resistance to oxaliplatin limits its therapeutic efficacy, and the underlying mechanism remains largely unclear. In this study, we compared the expression of a panel of microRNAs (miRNAs) between oxaliplatin-sensitive and -resistant HCT-116 colorectal cancer cells. We found that miR-454-3p was significantly up-regulated in oxaliplatin-resistant cells and was the most differently expressed miRNA. Interestingly, we observed that inhibition of miR-454-3p resensitized resistant cells to oxaliplatin and enhanced oxaliplatin-induced cellular apoptosis. Moreover, we determined that miR-454-3p promoted oxaliplatin resistance through targeting PTEN and activating the AKT signaling pathway. study revealed that overexpression of miR-454-3p decreased the sensitivity of HCT-116 xenograft tumors to oxaliplatin treatment in a mouse model. Clinically, overexpression of miR-454-3p was associated with decreased responsiveness to oxaliplatin-based chemotherapy, as well as a short progression-free survival. Taken together, our study indicated that the expression of miR-454-3p could be used to predict oxaliplatin sensitivity, and targeting miR-454-3p could overcome oxaliplatin resistance in colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.638537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129568PMC
May 2021

Prognostic value of ferroptosis-related genes in patients with lung adenocarcinoma.

Thorac Cancer 2021 Jun 12;12(12):1890-1899. Epub 2021 May 12.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: The prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.

Methods: We retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.

Results: Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.

Conclusions: The FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201541PMC
June 2021

Chlorogenic acid is a positive regulator of MDA5, TLR7 and NF-κB signaling pathways mediated antiviral responses against Gammacoronavirus infection.

Int Immunopharmacol 2021 Jul 7;96:107671. Epub 2021 May 7.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

Chlorogenic acid (CGA) is a phenolic compound that has been well studied for its antiviral, anti-inflammatory and immune stimulating properties. This research was aimed to focus on the antiviral properties of CGA on infectious bronchitis virus (IBV) in vivo and in vitro for the very first time. The outcome of in vitro experiments validated that, out of five previously reported antiviral components, CGA significantly reduced the relative mRNA expression of IBV-N in CEK cells. At high concentration (400 mg/kg), CGA supplementation reduced IBV-N mRNA expression levels and ameliorated the injury in trachea and lungs. The mRNA expression levels of IL-6, IL-1β, IL-12, and NF-κB were considerably turned down, but IL-22 and IL-10 were enhanced in trachea. However, CGA-H treatment had considerably increased the expression levels of MDA5, MAVS, TLR7, MyD88, IRF7, IFN-β and IFN-α both in trachea and lungs. Moreover, CGA-H notably induced the CD3+, CD3+ CD4+ and CD4+/CD8+ proliferation and significantly increased the IgA, IgG, and IgM levels in the serum. In conclusion, these results showed that at high concentration CGA is a strong anti-IBV compound that can effectively regulate the innate immunity through MDA5, TLR7 and NF-κB signaling pathways and have the potential to induce the cell mediated and humoral immune response in IBV infected chickens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.107671DOI Listing
July 2021

Primary ciliated muconodular papillary tumor: A rare pulmonary disease and literature review of 65 cases.

Thorac Cancer 2021 Jun 7;12(12):1917-1922. Epub 2021 May 7.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

A ciliated muconodular papillary tumor (CMPT) or bronchiolar adenoma (BA) is a rather rare and unique type of lung tumor characterized by tripartite cellular components with a papillary-predominant structure including ciliated columnar cells, mucinous cells, and basal cells. Here, we present the case of a 64-year-old woman who was diagnosed with CMPT in our center. In addition to reporting the clinicopathological characteristics of this case, we also conducted whole exome sequencing (WES) to explore the underlying mechanism. According to current evidence, CMPTs tends to be benign or of low grade malignancy. However, this requires further validation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201536PMC
June 2021

An update of new small-molecule anticancer drugs approved from 2015 to 2020.

Eur J Med Chem 2021 Aug 17;220:113473. Epub 2021 Apr 17.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, PR China.

A high incidence of cancer has given rise to the development of more anti-tumor drugs. From 2015 to 2020, fifty-six new small-molecule anticancer drugs, divided into ten categories according to their anti-tumor target activities, have been approved. These include TKIs (30 drugs), MAPK inhibitors (3 drugs), CDK inhibitors (3 drugs), PARP inhibitors (3 drugs), PI3K inhibitors (3 drugs), SMO receptor antagonists (2 drugs), AR antagonists (2 drugs), SSTR inhibitors (2 drugs), IDH inhibitors (2 drugs) and others (6 drugs). Among them, PTK inhibitors (30/56) have led to a paradigm shift in cancer treatment with less toxicity and more potency. Each of their structures, approval statuses, applications, SAR analyses, and original research synthesis routes have been summarized, giving us a more comprehensive map for further efforts to design more specific targeted agents for reducing cancer in the future. We believe this review will help further research of potential antitumor agents in clinical usage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2021.113473DOI Listing
August 2021

Differences in Lung Cancer Treatment Preferences Among Oncologists, Patients and Family Members: A Semi-Structured Qualitative Study in China.

Patient Prefer Adherence 2021 15;15:775-783. Epub 2021 Apr 15.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Background: Cancer treatment decision-making often needs to balance benefits, harms, and costs. This study sought to identify the differences in cancer treatment preference among oncologists, patients and their family members in China.

Methods: A semi-structured face-to-face qualitative interview was conducted among oncologists, patients and their family members recruited in four tertiary hospitals in China. The interview guide was developed based on literature review and expert consultation. Participants were asked to indicate their preferences when making lung cancer treatment decisions. All interviews were audio-taped, transcribed verbatim, and thematic analyzed. The preferences were compared among three groups of participants.

Results: A total of 17 participants (5 oncologists, 6 dyads of patients and family members) were interviewed between June and July 2019. Five themes, namely, survival benefit, adverse effect/symptom, treatment process, treatment cost, and the impact on daily life were identified. The oncologists and family members gave highest priority on survival benefit, while the patients are concerned most about treatment cost and quality of life.

Conclusion: This study reveals different preferences for cancer treatment among oncologists, patients and their family members in China. Education is needed to empower patients and family members and promote share decision-making in this country.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/PPA.S299399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055254PMC
April 2021

New pectic polysaccharides from Codonopsis pilosula and Codonopsis tangshen: structural characterization and cellular antioxidant activities.

J Sci Food Agric 2021 Apr 15. Epub 2021 Apr 15.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Background: Codonopsis pilosula and Codonopsis tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from the roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography.

Results: The core structures of both CPP-1 and CTP-1 comprise the long homogalacturonan region (HG) as the backbone and the rhamnogalacturonan I (RG-I) region as the side chains. CPP-1 has methyl esterified galacturonic acid units and a slightly lower molecular weight than CTP-1. Biological testing suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H O -induced oxidative stress by up-regulating nuclear factor-erythroid 2-related factor 2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of differences in their structures.

Conclusion: All of the results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. © 2021 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsfa.11261DOI Listing
April 2021

Clinical analysis of seven pediatric patients with coronavirus disease 2019 (COVID-19) in Jingzhou, Hubei, China: a retrospective study.

Transl Pediatr 2021 Mar;10(3):616-624

Department of Pediatrics, The First Affiliated Hospital of Yangtze University, Jingzhou, China.

Background: The novel coronavirus disease 2019 (COVID-19) epidemic has spread globally, along with its incidence among children. The purpose of this study was to evaluate the clinical characteristics and outcomes of children infected with COVID-19 and to provide a reference for clinical work.

Methods: The study retrospectively reviewed the clinical characteristics and prognosis of 7 children diagnosed with COVID-19 infection at The First People's Hospital of Jingzhou between January 30 and February 29, 2020.

Results: Of the 7 cases, 2 were male and 5 were female, aged 3 months and 14 days to 12 years old (median age 3 years old). There was 1 asymptomatic carrier, 5 cases with mild type infection, which had the main symptoms of cough (4/5) and fever (4/5), and 1 case of moderate type. Among the 7 cases, serum white blood cell count was increased in 1 case, decreased in 1 case, liver transaminase was increased in 1 case, lactate dehydrogenase was increased in 3 cases, creatine kinase MB (CK-MB) was increased in 2 cases, and C-reactive protein was elevated in 2 cases. A total of 4 cases were complicated with mycoplasma pneumoniae and/or influenza B virus infection. A single case of chest computed tomography (CT) showed viral pneumonia. With routine antiviral and symptomatic support therapy, the median time taken for the results of nucleic acid testing by pharyngeal swab to become negative was 14 days (6-26 days) and the median hospital stay was 15 days (8-31 days). All participants were cured and subsequently discharged from hospital. Only 1 case was positive for nucleic acid testing by pharyngeal swab 1 month after being discharged, and the anal swab of 1 case for nucleic acid testing was positive 2 months after being discharged.

Conclusions: All children with COVID-19 who were included in this study in Jingzhou were infected via family clustering, and the laboratory examinations were not specific. Fever and cough were common symptoms, but all cases were mild and had good prognoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tp-21-48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039793PMC
March 2021

Mutations Associated with No Durable Clinical Benefit to Immune Checkpoint Blockade in Non-S-Cell Lung Cancer.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300050, China.

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13061397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003499PMC
March 2021

Postoperative pain control with continuous paravertebral nerve block and intercostal nerve block after two-port video-assisted thoracic surgery.

Wideochir Inne Tech Maloinwazyjne 2021 Mar 25;16(1):273-281. Epub 2020 Sep 25.

Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo,, China.

Introduction: Effective pain control after video-assisted thoracic surgery (VATS) is critical because of the correlation between postoperative pain and recovery after surgery. Due to the limitations of traditional analgesic modalities, in this study, we present a method of placing a paravertebral catheter (PVC) or an intercostal catheter (ICC) in the sub-pleural space, followed by continuous ropivacaine injection by an infusion pump after surgery.

Aim: To investigate the impact of continuous paravertebral nerve block and intercostal nerve block on postoperative pain control in patients who underwent two-port thoracic surgery.

Material And Methods: A total of 269 patients underwent various types of two-port VATS at Hwa Mei Hospital. Among them, we retrospectively compared paravertebral block versus intercostal nerve block to intravenous patient-controlled analgesia after VATS. Data regarding postoperative pain score on postoperative day 0, 1, 2, 3, and discharge day pain score, tramadol requirements, drainage duration, postoperative hospital stay, postoperative complications, and chronic pain 3 months after surgery were collected and analyzed.

Results: Compared with the control group, patients who received a continuous nerve block, including the PVC group and ICC group, had a lower postoperative pain score (p < 0.001), shorter drainage duration (4.63 ±2.84 to 5.61 ±2.66 days, p = 0.004), reduced postoperative hospital stay (6.04 ±3.01 to 7.69 ±3.26 days, p < 0.001), and a reduced frequency of tramadol (0.95 ±1.27 1.79 ±2.13 times, p < 0.001). Additionally, there was no significant difference in chronic pain between groups.

Conclusions: In our study, PVC and ICC appeared to be safe and effective analgesic techniques to reduce postoperative pain, thus shortening the duration of postoperative hospital stay and improving the satisfaction of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5114/wiitm.2020.99349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991946PMC
March 2021

Japanese Encephalitis in China in the Period of 1950-2018: From Discovery to Control.

Biomed Environ Sci 2021 Mar;34(3):175-183

Department of Arbovirus, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3967/bes2021.024DOI Listing
March 2021

Application of mediastinal drainage tube in intrathoracic esophageal anastomotic leakage for early diagnosis and effective treatment: a retrospective study.

J Cardiothorac Surg 2021 Mar 25;16(1):52. Epub 2021 Mar 25.

Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Background: Intrathoracic esophageal anastomotic leakage (AL) is one of the most fatal complications after esophagectomy. In this study, we placed an additional drainage tube in the esophagus bed and evaluated its effect in early diagnosis and treatment of AL.

Methods: From January 2010 to August 2020, 312 patients with esophageal or cardia carcinoma underwent esophageal resection with intrathoracic esophagogastric anastomosis. A total of 138 patients with only one pleural drainage tube were divided into the "Control Group" and 174 patients with a pleural drainage tube and an additional mediastinal drainage tube (MDT) were divided into the "Tube Group". For all patients, the incidence of postoperative AL, the time to diagnosis, time to recovery, and patient outcome were analyzed.

Results: No significant differences were observed in the AL rate (P = 0.837) and postoperative pain between two groups. However, in the Tube Group, almost all the patients were diagnosed prior to the appearance of hyperpyrexia, which was considered as the earliest and most common symptom after AL. In the Tube Group, a significant decrease was observed in the incidence of incurable fistula, which required re-operation or variable treatments under gastroscopy when compared to the Control Group (P = 0.032). Finally, patients in the Tube Group showed reduced post AL hospital day (P = 0.015) and a lower mortality, however, when compared to the Control Group, no significant differences were observed (P = 0.188).

Conclusions: Placement of an MDT does not prevent AL, but it is an effective approach for earlier diagnosis of AL and facilitates fistula healing and patient recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13019-021-01435-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993533PMC
March 2021

Diagnostic Role of Long Non-Coding RNAs in Breast Cancer: a Systematic Review and Meta-Analysis.

Clin Lab 2021 Mar;67(3)

Background: Recent research has suggested that long non-coding RNA (lncRNA) is involved in the tumorigenesis and development of breast cancer (BC). This meta-analysis aimed to identify the diagnostic role of lncRNAs in BC.

Methods: All relevant studies were systematically searched through PubMed, Web of Science, Cochrane Library, and EMBASE databases. The diagnostic values of lncRNAs were mainly assessed by pooled sensitivity (SEN), specificity (SPE), and summary receiver operating characteristic area under the curve (SROC AUC). Meta-DiSc 1.4, Review Manager 5.3 and STATA 12.0 were used for statistical analysis.

Results: A total of 24 eligible studies were included in this meta-analysis. The pooled SEN, SPE, and AUC were 0.75 (95% CI: 0.68 - 0.81), 0.77 (95% CI: 0.70 - 0.82), and 0.82 (95% CI: 0.79 - 0.86), respectively, suggesting that the lncRNAs test had a high accuracy for the diagnosis of BC. Obvious heterogeneity might come from the dysregulated state of lncRNAs through subgroup and meta-regression analysis (p < 0.001). Fagan diagram showed clinical value of lncRNAs test in BC.

Conclusions: Abnormal expression of lncRNAs exhibits a high efficacy for diagnosing BC, which is promising in clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2020.200662DOI Listing
March 2021

Multidimensional crosstalk between RNA-binding proteins and noncoding RNAs in cancer biology.

Semin Cancer Biol 2021 Mar 16. Epub 2021 Mar 16.

Center for Functional Genomics and Bioinformatics, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China. Electronic address:

RNA-binding proteins (RBPs) are well-known to bind RNA via a set of RNA-binding domains (RBDs) and determine the fate and function of their RNA targets; inversely, some RBPs, in certain cases, may be modulated by the bound RNAs rather than regulate their RNA partners. Current proteome-wide studies reveal that almost half of RBPs have no canonical RBDs, and the discovery of tens of thousands of noncoding RNAs (ncRNAs), especially those with the size larger than 200 nt (namely long noncoding RNAs, lncRNAs), makes the crosstalk between RBPs and RNAs more complicated. It is clear that macromolecular complexes formed by RBP and RNA are not only a form of existence of their RBP and RNA components in cells, but also represent a functional entity through which those RBPs and regulatory ncRNAs participate in the construction of regulatory networks in organism. In this review, we summarize the multidimensional crosstalk between RBPs and ncRNAs in cancer and discuss how RBPs achieve their function via the bound ncRNAs in different aspects of gene expression as well as how RBPs direct modification and processing of ncRNAs, in order to better understand tumor biology and provide new insights into development of strategies for cancer therapy and early detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semcancer.2021.03.007DOI Listing
March 2021

The Impact of Programmed Death-Ligand 1 Expression on the Prognosis of Early Stage Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Literatures.

Front Oncol 2021 23;11:567978. Epub 2021 Feb 23.

Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.

Introduction: Previous studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.

Methods: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.

Results: A total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18-2.05, p < 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29-2.18, p < 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male female: OR = 1.27, 95% CI:1.01-1.59, p = 0.038), histology (ADC . SCC: OR = 0.54, 95% CI:0.38-0.77, p = 0.001), TNM stage (I . II-III: OR = 0.45, 95% CI:0.34-0.60, p = 0.000), smoking status (Yes No: OR = 1.43, 95% CI:1.14-1.80, p = 0.002) and lymph node metastasis (N+ N-: OR = 1.97, 95% CI:1.26-3.08, p = 0.003).

Conclusions: The results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.567978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940546PMC
February 2021

Tannins extract from Galla Chinensis can protect mice from infection by Enterotoxigenic Escherichia coli O101.

BMC Complement Med Ther 2021 Mar 6;21(1):84. Epub 2021 Mar 6.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.

Background: Enterotoxigenic Escherichia coli (ETEC) is classically associated with acute secretory diarrhea, which induces 2 million people death in developing countries over a year, predominantly children in the first years of life. Previously, tannins (47.75%) were extracted from Galla Chinensis and prepared as Galla Chinensis oral solution (GOS) which showed significant antidiarrheal activity in a castor oil-induced diarrhea in mice. Whether the tannins extract were also effective in treatment of ETEC-induced diarrhea was determined in this study.

Methods: Mice were randomly divided into 6 groups (n = 22). The mice in the normal and untreated groups were given normal saline. Three GOS-treated groups were received different concentrations of GOS (5, 10 and 15%, respectively) at a dose of 10 mL/kg. Mice in the positive control group were fed with loperamide (10 mg/kg). The treatment with GOS started 3 days before infection with ETEC and continued for 4 consecutive days after infection. On day 3, mice were all infected with one dose of LD of ETEC, except those in the normal group. Survival of mice was observed daily and recorded throughout the study. On days 4 and 7, samples were collected from 6 mice in each group.

Results: GOS could increase the survival rate up to 75%, while in the untreated group it is 43.75%. The body weights of mice treated with 15% GOS were significantly increased on day 7 in comparison with the untreated group and the normal group. GOS-treatment recovered the small intestine coefficient enhanced by ETEC-infection. The diarrhea index of mice treated with GOS was significantly decreased. GOS increased the levels of IgG and sIgA in the terminal ileum and decreased the levels of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6 and IL-8) in serum. GOS could increase the amount of intestinal probiotics, Lactobacilli and Bifidobacteria. GOS could alleviate colon lesions induced by ETEC-infection. GOS showed higher potency than loperamide.

Conclusions: GOS could be a promising drug candidate for treating ETEC infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12906-021-03261-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937208PMC
March 2021

Polymeric Micelles in Cancer Immunotherapy.

Molecules 2021 Feb 25;26(5). Epub 2021 Feb 25.

Institute of Regulatory Science for Medical Device, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

Cancer immunotherapies have generated some miracles in the clinic by orchestrating our immune system to combat cancer cells. However, the safety and efficacy concerns of the systemic delivery of these immunostimulatory agents has limited their application. Nanomedicine-based delivery strategies (e.g., liposomes, polymeric nanoparticles, silico, etc.) play an essential role in improving cancer immunotherapies, either by enhancing the anti-tumor immune response, or reducing their systemic adverse effects. The versatility of working with biocompatible polymers helps these polymeric nanoparticles stand out as a key carrier to improve bioavailability and achieve specific delivery at the site of action. This review provides a summary of the latest advancements in the use of polymeric micelles for cancer immunotherapy, including their application in delivering immunological checkpoint inhibitors, immunostimulatory molecules, engineered T cells, and cancer vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26051220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956602PMC
February 2021

Core-shell [email protected](In) derived ZnO nanoparticles-embedded InO hollow tubular with oxygen vacancy for photocatalytic degradation of antibiotic pollutant.

J Hazard Mater 2021 07 17;414:125395. Epub 2021 Feb 17.

Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, PR China; School of Environmental & Safety Engineering, Changzhou University, Changzhou 213164, PR China. Electronic address:

Developing a novel core-multishelled metal oxide hollow tube with rich oxygen vacancy is highly attractive in photocatalytic degradation of antibiotic pollutant. Herein, [email protected] core-shell hollow microtubes were synthesized via one-step calcination of [email protected](In) formed by an in-situ self-assembly. TEM images demonstrate that 0D ZnO quantum dots (QDs) shell with 0.2 µm were well coated on the surface of 1D InO hollow tube as the core with 1.2 µm. The synthesized heterostructure indicates the enhanced photocatalytic performance in tetracycline (TC) degradation compared with single ZIF-derived ZnO and MIL-68(In)-derived InO under simulated solar irradiation. Besides, organic pollutants including malachite green (MG), methylene blue (MB) and rhodamine B (RhB) are further used to evaluate the photocatalytic activity of [email protected], and the effect of weight ratios between ZnO and InO on degradation efficiency is also studies. The [email protected] heterojunction can provide higher specific surface area, expose more active sites, possess appropriate number of oxygen vacancies, enhance light absorption and further effectively boost the transfer and separation of photoinduced charge carriers. In addition, the proposed photocatalytic mechanism and degradation pathway are discussed in detail based on active species trapping test, electron spin resonance (ESR) and LCMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.125395DOI Listing
July 2021

Possible treatment for UVB-induced skin injury: Anti-inflammatory and cytoprotective role of metformin in UVB-irradiated keratinocytes.

J Dermatol Sci 2021 Apr 9;102(1):25-35. Epub 2021 Feb 9.

Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China. Electronic address:

Background: Excessive inflammation and cell death induced by ultraviolet (UV) cause skin photodamage. Metformin possesses anti-inflammatory and cytoprotective effects. However, whether metformin inhibits inflammation and cell death in UVB-induced acute skin damage is unclear.

Objective: To evaluate the anti-inflammatory and cytoprotective effects of metformin in vitro and in vivo. Furthermore, its potential mechanism has been explored.

Methods: Transcriptome sequencing and multiplex cytokines analysis were used to evaluate the validity of in vitro UVB-induced acute damage keratinocyte model and anti-inflammatory effects of metformin. We also determined the expression and nuclear translocation of CCAAT/enhancer-binding protein beta (C/EBPβ), an important transcriptional factor of Interleukin-1beta (IL-1β). Cell viability and cell death of keratinocytes were evaluated upon UVB irradiation in the presence or absence of metformin. 0.6% metformin cream was applied on UVB-irradiated mice to explore its pharmacological effects in vivo.

Results: Transcriptional landscape of 50 mJ/cm UVB-irradiated HaCaT cells is typical of UVB-induced acute damage keratinocyte model in vitro. Metformin alleviated transcription and secretion of IL-1β, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPβ in this model. Metformin also protected keratinocytes from cell death caused by UVB-induced cellular secretions, which contributed to its cytoprotective effects. Topical administration of 0.6% metformin cream alleviated UVB-induced skin damage in mice.

Conclusion: We proved the protective roles of metformin in UVB-challenged keratinocytes and UVB-irradiated mice, which indicated the potential value of metformin in topical therapy against skin photodamage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdermsci.2021.02.002DOI Listing
April 2021

Synthesis and structure-activity relationship of lipo-diterpenoid alkaloids with potential target of topoisomerase IIα for breast cancer treatment.

Bioorg Chem 2021 Apr 8;109:104699. Epub 2021 Feb 8.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China.

Aconitine linoleate (11) isolated from the Aconitum sinchiangense W. T. Wang exhibited significant anti-tumor activity. Based on this, a series of novel lipo-diterpenoid alkaloids were synthesized and evaluated for their anticancer activities against MCF-7 and MCF-7/ADR cell lines. Seventeen compounds, including 18-20, 22, 24-32, 36, 39, 41-42 possessed higher anti-proliferative activities (IC < 20 μM) against MCF-7 cell lines, which were better than the reference drug etoposide (IC = 18.01 ± 1.64 μM), among which compound 24 (IC = 4.00 ± 0.30 μM) was found to be the most potent derivative, being 4.5-fold more active than etoposide. Meanwhile, eighteen compounds, including 18-22, 24, 26-32, 36, 38-39, 41-42 presented excellent activities (IC < 20 μM) against MCF-7/ADR cell lines, better than etoposide (IC = 35.48 ± 0.29 μM) and doxorubicin (IC = 67.61 ± 6.5 μM). The most potent compound (19) was 13.5- and 25.7-fold more active than etoposide and doxorubicin against MCF-7/ADR cell lines, respectively. The structure-activity relationship (SAR) studies indicated that the 3-OH, 8-lipo, 14-benzene ring, and nitrogen atom with proper alkaline are crucial elements for anti-proliferative activity of target lipo-diterpenoid compounds. The proper length, the double bonds or di-fluoro-substituted at C-8 fatty acid chain, the para-donating electron group on 14-benzene group, and 13-OH are all favorable for the enhancement of anti-proliferative activities. In conclusion, the introduction of the 8-lipo group into aconitine leads to significant increase of anti-proliferative activity against MCF-7 and MCF-7/ADR cells, which suggests these kinds of lipo-alkaloids are powerful and promising antitumor compounds for breast cancer, especially for drug-resistant breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.104699DOI Listing
April 2021