Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Spatio-temporal analysis of toxigenic genes expression in the growing Bufo gargarizans based on RNA sequencing data.

BACKGROUND: Bufo gargarizans Cantor, a widely distributed amphibian species in Asia, produces and releases toxins through its retroauricular and granular glands. Although various tissues have been sequenced, the molecular mechanisms underlying the toxin production remain unclear. To elucidate these mechanisms, abdominal skin (non-toxic secretory glands) and retroauricular gland (toxic secreting glands) samples were collected at different time points (3, 6, 12, 24, and 36 months) for RNA sequencing (RNA-seq) and analysis. RESULTS: In comparison to the S group during the same period, a total of 3053, 3026, 1516, 1028, and 2061 differentially expressed genes (DEGs) were identified across five developmental stages. Gene Ontology (GO) analysis revealed that DEGs were primarily enriched in biological processes including cellular processes, single-organism processes, metabolic processes, and biological regulation. In terms of cellular components, the DEGs were predominantly localized in the cell and cell parts, whereas molecular function indicated significant enrichment in binding and catalytic activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the metabolism and synthesis of various substances, such as lipid metabolism, cofactor and vitamin metabolism, tryptophan metabolism, steroid biosynthesis, and primary bile acid biosynthesis, were accompanied by the development of toads. Additionally, using trend analysis, we discovered candidate genes that were upregulated in the retroauricular glands during development, and the abundance of these genes in the abdominal skin was extremely low. Finally, we identified 26 genes that are likely to be involved in toxin production and that are likely to be involved in toxin anabolism. CONCLUSION: Overall, these results provide new insights into the genes involved in toxin production in B. gargarizans, which will improve our understanding of the molecular mechanisms underlying toxigenic gene expression.

Qi-dan-dihuang decoction ameliorates renal fibrosis in diabetic rats via p38MAPK/AKT/mTOR signaling pathway.

CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND METHODS: The compounds in QDD were identified by high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD-low (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. RESULTS: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.

Efficacy and safety of moxibustion for ulcerative colitis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ulcerative colitis (UC) is a global chronic inflammatory bowel disease, and the poor efficacy of currently available pharmacological regimens makes the management of UC a great challenge. Moxibustion has shown great potential in the management of UC. However, its effectiveness and safety are still controversial. The purpose of this study is to synthesise the latest evidence regarding the clinical efficacy and safety of moxibustion for UC. METHODS AND ANALYSIS: The Cochrane Library, PubMed, EMBASE, CNKI, Wanfang, VIP and SinoMed databases will be searched from inception to July 2023, to identify all randomised controlled trials with moxibustion for UC. The primary outcome will be clinical efficacy, as measured by validated scales. The serum inflammatory factor, colonoscopy results, quality of life, recurrence rate and adverse events will be the secondary outcomes. The Cochrane Risk of Bias 2.0 tool will be used to assess the methodological quality of each included trial. All data extraction will be carried out independently by two investigators. RevMan V.5.4 software will be used for data analysis and Cochran's Q statistic and I2 test will be used to assess heterogeneity between studies. In addition, we will perform subgroup analyses, sensitivity analyses and publication bias if the available data are sufficient. The strength of evidence will be graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: Ethics approval is not required for this review. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023425481.

Research progress on the structure, derivatives, pharmacological activity, and drug carrier capacity of Chinese yam polysaccharides: A review.

Chinese yam is a traditional Chinese medicine that has a long history of medicinal and edible usage in China and is widely utilised in food, medicine, animal husbandry, and other industries. Chinese yam polysaccharides (CYPs) are among the main active components of Chinese yam. In recent decades, CYPs have received considerable attention because of their remarkable biological activities, such as immunomodulatory, antitumour, hypoglycaemic, hypolipidaemic, antioxidative, anti-inflammatory, and bacteriostatic effects. The structure and chemical alterations of polysaccharides are the main factors affecting their biological activities. CYPs are potential drug carriers owing to their excellent biodegradability and biocompatibility. There is a considerable amount of research on CYPs; however, a systematic summary is lacking. This review summarises the structural characteristics, derivative synthesis, biological activities, and their usage as drug carriers, providing a basis for future research, development, and application of CYPs.

Catalpol antagonizes LPS-mediated inflammation and promotes osteoblast differentiation through the miR-124-3p/DNMT3b/TRAF6 axis.

BACKGROUND: Dysregulated inflammation and osteoblast differentiation are implicated in osteoporosis. Exploring the activity of catalpol in inflammation and osteoblast differentiation deepens the understanding of osteoporosis pathogenesis. METHODS: LPS was used to treated hFOB1.19 cells to induce inflammation and repress osteoblast differentiation. FOB1.19 cells were induced in osteoblast differentiation medium and treated with LPS and catalpol. Cell viability was assessed using CCK-8. ALP and Alizarin red S staining were conducted for analyzing osteoblast differentiation. The levels of IL-1ß, TNF-α and IL-6 were examined by ELISA. The methylation of TRAF6 promoter was examined through MS-PCR. The binding of miR-124-3p to DNMT3b and DNMT3b to TRAF6 promoter was determined with dual luciferase reporter and ChIP assays. RESULTS: LPS enhanced secretion of inflammatory cytokines and suppressed osteoblast differentiation. MiR-124-3p and TRAF6 were upregulated and DNMT3b was downregulated in LPS-induced hFOB1.19 cells. Catalpol protected hFOB1.19 cells against LPS via inhibiting inflammation and promoting osteoblast differentiation. MiR-124-3p targeted DNMT3b, and its overexpression abrogated catalpol-mediated protection in LPS-treated hFOB1.19 cells. In addition, DNMT3b methylated TRAF6 promoter to restrain its expression. Catalpol exerted protective effects through suppression of the miR-124-3p/DNMT3b/TRAF6 axis in hFOB1.19 cells. CONCLUSION: Catalpol antagonizes LPS-mediated inflammation and suppressive osteoblast differentiation via controlling the miR-124-3p/DNMT3b/TRAF6 axis.

Enhancing doctor-patient relationships in community health care institutions: the Patient Oriented Four Habits Model (POFHM) trial-a stepped wedge cluster randomized trial protocol.

BACKGROUND: The poor relationship between doctors and patients is a long-standing, global problem. However, current interventions tend to focus on the training of physicians, while patient-targeted interventions still need to be improved. Considering that patients play a significant role in outpatient consultations, we developed a protocol to assess the effectiveness of the Patient Oriented Four Habits Model (POFHM) in improving doctor-patient relationships. METHODS: A cross-sectional incomplete stepped-wedge cluster randomized trial design will be conducted in 8 primary healthcare institutions (PHCs). Following phase I of "usual care" as control measures for each PHC, either a patient- or doctor-only intervention will be implemented in phase II. In phase III, both patients and doctors will be involved in the intervention. This study will be conducted simultaneously in Nanling County and West Lake District. The primary outcomes will be evaluated after patients complete their visit: (1) patient literacy, (2) sense of control and (3) quality of doctor-patient communication. Finally, a mixed-effects model and subgroup analysis will be used to evaluate the effectiveness of the interventions. DISCUSSION: Fostering good consultation habits for the patient is a potentially effective strategy to improve the quality of doctor-patient communication. This study evaluates the implementation process and develops a rigorous quality control manual using a theoretical domain framework under the collective culture of China. The results of this trial will provide substantial evidence of the effectiveness of patient-oriented interventions. The POFHM can benefit the PHCs and provide a reference for countries and regions where medical resources are scarce and collectivist cultures dominate. TRIAL REGISTRATION: AsPredicted #107,282 on Sep 18, 2022; https://aspredicted.org/QST_MHW.

Association of long-term particulate matter exposure with all-cause mortality among patients with ovarian cancer: A prospective cohort.

BACKGROUND: Evidence of the association between particles with a diameter of 2.5 µm or less (PM2.5) in long term and ovarian cancer (OC) mortality is limited. METHODS: This prospective cohort study analyzed data collected between 2015 and 2020 from 610 newly diagnosed OC patients, aged 18-79 years. The residential average PM2.5 concentrations 10 years before the date of OC diagnosis were assessed by random forest models at a 1 km × 1 km resolution. Cox proportional hazard models fully adjusted for the covariates (including age at diagnosis, education, physical activity, kitchen ventilation, FIGO stage, and comorbidities) and distributed lag non-linear models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of PM2.5 and all-cause mortality of OC. RESULTS: During a median follow-up of 37.6 months (interquartile: 24.8-50.5 months), 118 (19.34 %) deaths were confirmed among 610 OC patients. One-year PM2.5 exposure levels before OC diagnosis was significantly associated with an increase in all-cause mortality among OC patients (single-pollutant model: HR = 1.22, 95 % CI: 1.02-1.46; multi-pollutant models: HR = 1.38, 95 % CI: 1.10-1.72). Furthermore, during 1 to 10 years prior to diagnosis, the lag-specific effect of long-term PM2.5 exposure on the all-cause mortality of OC had a risk increase for lag 1-6 years, and the exposure-response relationship was linear. Of note, significant interactions between several immunological indicators as well as solid fuel use for cooking and ambient PM2.5 concentrations were observed. CONCLUSION: Higher ambient PM2.5 concentrations were associated with an increased risk of all-cause mortality among OC patients, and there was a lag effect in long-term PM2.5 exposure.

Prediagnosis Depression Rather Than Anxiety Symptoms Is Associated with Decreased Ovarian Cancer Survival: Findings from the Ovarian Cancer Follow-Up Study (OOPS).

Background: The relationship between prediagnosis depression, anxiety symptoms, and ovarian cancer (OC) survival is unknown. We aimed to explore these associations to provide further epidemiological evidence. Methods: We investigated the relationship between prediagnosis depression, anxiety symptoms, and OC survival in a prospective cohort study of newly diagnosed OC patients aged 18−79 years. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire 9 and Generalized Anxiety Disorder 7 at diagnosis, respectively. Deaths were ascertained until 31 March 2021 via medical records and active follow-up. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with prediagnosis depression and anxiety symptoms and all-cause mortality of OC. Results: We found 56 (9.4%) and 235 (39.3%) OC patients with depression and anxiety symptoms, respectively. During a median follow-up of 37.2 months (interquartile range 24.7−50.2 months), 130 deaths were confirmed. Compared with non-depression symptoms, patients with prediagnosis depressive symptoms showed a significantly increased risk of OC mortality (HR = 2.10, 95% CI: 1.20−3.70). Of note, the association was still robust when focusing on the OC patients with severe depressive symptoms (HR = 2.10, 95% CI: 1.07−4.12). However, we observed no association between prediagnosis anxiety symptoms of different severity and OC mortality. Interestingly, OC patients with combined moderate depression and anxiety symptoms had a significantly increased risk of OC mortality (HR = 3.23, 95% CI: 1.14−9.11) compared to those with no symptoms of depression and anxiety. Notably, Wilms's tumor 1 was significantly associated with depression and anxiety symptoms (p < 0.05). Conclusions: Prediagnosis depression increases the risk of OC mortality. Large multicenter studies are required to confirm this finding.

V2CTx MXene as novel anode for aqueous asymmetric supercapacitor with superb durability in ZnSO4 electrolyte.

Despite of great interests in aqueous asymmetric supercapacitors (ASC), their performance is often restricted by unsatisfactory specific capacitance of anode materials. Herein, accordion-like V2CTx MXene has been prepared and exploited as novel anode material for aqueous ASC in neutral ZnSO4 electrolyte. Profitting from the layered structure with expanded interlayer distance, the V2CTx electrode exhibits a high specific capacitance of 481F g-1 at 1 A g-1, a reasonable rate performance and intriguing cycling stability with capacitance retention of 84.3% after 60,000 cycles at 10 A g-1 in 2 M ZnSO4 electrolyte. Furthermore, an ASC device based on the V2CTx as anode and activated carbon (AC) as cathode was successfully assembled in the ZnSO4 electrolyte, which achieves a wide potential window up to 1.8 V. Remarkably, the V2CTx//AC ASC delivers a high energy density of 34 W h kg-1 at a power density of 954 W kg-1, as well as superb cycling stability with capacitance retention of 79% even after 100,000 charge/discharge cycles at 10 A g-1. The intriguing electrochemical performance, especially the ultralong cycling life, make the V2CTx MXene electrode promising in aqueous energy storage devices.

Regulating Sn self-doping and boosting solar water splitting performance of hematite nanorod arrays grown on fluorine-doped tin oxide via low-level Hf doping.

Hematite (α-Fe2O3) nanorod arrays grown on fluorine-doped tin oxide (FTO) substrate exhibit outstanding solar water splitting efficiency, benefiting from Sn self-doping induced by high-temperature annealing. However, this Sn self-doping couldn't be freely controlled without changing the optimized annealing conditions, which limits the further improvement of their photoelectrochemical (PEC) properties. Here, we report a facile hydrothermal synthesis with subsequent annealing approach to regulate the Sn diffusion via hafnium (Hf) doping as well as enhance the PEC performance of hematite photoanode. Upon increasing the Hf doping concentration, the Sn self-doping content was continuously suppressed. The very low doping-level of Hf (i.e., atomic Hf/Fe = 0.13 âˆ¼ 1.54%) was sufficient for enhancing the electrical conductivity. The Hf-doped α-Fe2O3 with the optimized dopant concentration (Hf/Fe = 1.34%, denoted as 0.25-Hf-Fe2O3) showed a photocurrent density of 1.79 mA/cm2 at 1.23 V vs. RHE, 70% higher than that of the Sn self-doped one (Pristine-Fe2O3). The donor density of 0.25-Hf-Fe2O3 increased 2.5 times compared to Pristine-Fe2O3 while its space-charge resistance and charge transfer resistance declined by 40% and 22%, respectively, verifying Hf doping improves the charge carrier density and accelerates the charge transfer for solar water oxidation. We offered here a prospective dopant alternative for preparing superior hematite-based photoanode.

Downregulation of CPT1A exerts a protective effect in dextran sulfate sodium-induced ulcerative colitis partially by inhibiting PPARα signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may progress to colorectal cancer in severe cases. Carnitine palmitoyltransferase-1A (CPT1A) has been reported to be upregulated in colorectal cancer. This paper aims to explore the role of CPT1A in UC and its pathogenesis. An in vivo mice model of UC was constructed by administrating 3% dextran sulfate sodium (DSS). The expression level of CPT1A was examined by quantitative real-time polymerase chain reaction and Western blot. The intestinal damage, inflammatory response and oxidative stress were assessed by hematoxylin and eosin staining, colon length, and commercial kits. Thereafter, an in vitro cell model of UC was established by stimulating HT-29 cells with 2% DSS. The peroxisome proliferator-activated receptor α (PPARα) signaling agonist GW7647 was used for treatment. Cell viability and apoptosis was assayed by cell counting kit-8 assay and terminal dUTP nick-end labeling assay, respectively. The inflammatory cytokines and oxidative stress-related factors was evaluated using corresponding commercial detection kits. In DSS-induced mice model of UC, CPT1A expression was upregulated. Interference of CPT1A attenuated histological damage, the disease activity index and colon length in colitis. We also found downregulation of CPT1A inhibited inflammatory response and oxidative stress, and inhibited PPARα signaling pathway in UC mice. Additionally, in DSS-induced HT-29 cells, downregulation of CPT1A promoted cell viability, reduced cell apoptosis, inflammatory response, and oxidative stress, which was partly abolished by additional treatment with GW7647. In summary, downregulation of CPT1A exerts a protective effect in DSS-induced UC partially through suppressing PPARα signaling, suggesting that CPT1A might be a potential target for the treatment of UC.

Status of traditional Chinese medicine healthcare services in nursing homes across China.

This study aimed to elucidate the status of traditional Chinese medicine (TCM) healthcare services provided in nursing homes across China. We investigated 484 nursing homes using self-compiled questionnaires with a convenient sampling method. Chi-squared and Wilcoxon rank-sum tests were used for univariate analysis and binary logistic regression for multi-factor analysis. Of the 443 nursing homes finally included, 215 (48.5%) provided TCM healthcare services. Nursing home leaders majored in integrated TCM and Western medicine, leaders with a better understanding of TCM and government policies, nursing homes charging over 5,000 CNY/month, and those with ≥500 beds were more likely to provide improved TCM healthcare services. Massage, moxibustion, cupping or scraping, plaster therapy, decocting pieces, and acupuncture were the most prevalent and popular TCM services. Lack of professionals, financial investment, and policy support were the most common factors limiting the provision of TCM healthcare services in Chinese nursing homes.

Crumpled graphene microspheres anchored on NiCo2O4 nanoparticles as an advanced composite electrode for asymmetric supercapacitors with ultralong cycling life.

The rational design of composite electrodes that may take full advantage of pseudocapacitive metal oxides and graphene is still challenging. Herein, nickel cobaltate (NiCo2O4) nanoparticle-anchored crumpled graphene microspheres (CGMs) were fabricated through a simple spray-assisted self-assembly process and used as a composite electrode for aqueous supercapacitors. Due to the porous spherical architecture and well-dispersed NiCo2O4 nanoparticles on graphene, the NiCo2O4/CGM electrode displays ideal electrochemical performance, including a specific capacitance of 369.8 F g-1 (at 1 A g-1), good rate performance of 85% capacitance retention even at 10 A g-1 and intriguing cycling stability. An aqueous asymmetric supercapacitor (ASC) with an operating voltage of 1.6 V was then assembled using the NiCo2O4/CGM composite and nitrogen-doped CGM (N-CGM) as the positive and negative electrodes in KOH electrolyte, respectively. The ASC device exhibited an excellent energy density of 24.7 W h kg-1 at a power density of 799.6 W kg-1, and an ultralong cycling life with a capacitance retention of 85% after 50 000 cycles. The satisfactory electrochemical performance and ultralong cycling stability indicate that the NiCo2O4/CGM electrode has promising applications in advanced supercapacitors.

Fe3O4 nanoplates anchored on Ti3C2Tx MXene with enhanced pseudocapacitive and electrocatalytic properties.

Ti3C2Tx, as novel members of the two-dimensional material family, hold great promise for electrochemical energy storage and catalysis, however, the electrochemical performance of Ti3C2Tx is largely limited by the self-restacking of their layers due to van der Waals forces. In this study, we report a high-performance electrode material, Ti3C2Tx supported Fe3O4 nanoplates (denoted as MXene-Fe), synthesized by a simple in situ wet chemistry method in a solvothermal system. The mesoporous MXene-Fe material as a supercapacitor electrode exhibits a high specific capacitance of 368.0 F g-1 at 1.0 A g-1 and long cycling stability with about 81% capacitance retention after 10 000 cycles at 10.0 A g-1. Moreover, the optimized MXene-Fe also displays high electrocatalytic activity and stability toward the oxygen evolution reaction in alkaline solution (1.0 M KOH) with a low overpotential of 290 mV at 10 mA cm-2 and a small Tafel slope of 65.1 mV dec-1. This work provides an effective strategy for developing novel Ti3C2Tx-based functional materials with outstanding electrochemical performance for supercapacitors and electrocatalysis.

CircCTNNA1 acts as a ceRNA for miR-363-3p to facilitate the progression of colorectal cancer by promoting CXCL5 expression.

BACKGROUND: Circular RNAs (circRNA) have been shown to be involved in the pathogenesis of colorectal cancer (CRC). CircCTNNA1 was found to be one of the upregulated circRNAs in CRC. However, there are few studies on circCTNNA1, so it is necessary to carry out further studies. METHODS: The expression of circCTNNA1, microRNA (miR)-363-3p, and chemokine C-X-C motif ligand 5 (CXCL5) was detected by quantitative real-time PCR (qRT-PCR). The protein levels of CXCL5 and metastasis markers were measured using western blot (WB) analysis. Cell proliferation, apoptosis, cell cycle, migration, and invasion were determined by cell counting kit 8 (CCK8) assay, colony formation assay, flow cytometry, and transwell assay. The relationship between miR-363-3p and circCTNNA1 or CXCL5 was evaluated via dual-luciferase reporter assay and RNA immunoprecipitation assay. Animal study was performed to explore the function of circCTNNA1 on CRC tumorigenesis. RESULTS: CircCTNNA1 and CXCL5 were highly expressed in CRC. Knockdown of circCTNNA1 could inhibit the proliferation, cell cycle, metastasis, and promote the apoptosis of CRC cells. MiR-363-3p could be sponged by circCTNNA1, and the inhibition effect of circCTNNA1 silencing on CRC progression could be reversed by miR-363-3p inhibitor. Moreover, miR-363-3p could interact with CXCL5, and CXCL5 overexpression also could reverse the suppressive effect of miR-363-3p on CRC progression. Downregulation of circCTNNA1 also could hinder the tumor growth of CRC in vivo. CONCLUSION: CircCTNNA1 enhanced CRC progression via regulating the miR-363-3p/CXCL5 axis.

The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1.

BACKGROUND: Phosphatidylinositol-4-phosphate-binding protein GOLPH3L is overexpressed in human ductal carcinoma of the breast, and its expression levels correlate with the prognosis of breast cancer patients. However, the roles of GOLPH3L in breast tumorigenesis remain unclear. METHODS: We assessed the expression and biological function of GOLPH3L in breast cancer by combining bioinformatic prediction, metabolomics analysis and RNA-seq to determine the GOLPH3L-related pathways involved in tumorigenesis. Dual-luciferase reporter assay and coimmunoprecipitation (Co-IP) were used to explore the expression regulation mechanism of GOLPH3L. RESULTS: We demonstrated that knockdown of GOLPH3L in human breast cancer cells significantly suppressed their proliferation, survival, and migration and suppressed tumor growth in vivo, while overexpression of GOLPH3L promoted aggressive tumorigenic activities. We found that miRNA-1185-2-3p, the expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, is directly involved in suppressing the expression of GOLPH3L. Metabolomics microarray analysis and transcriptome sequencing analysis revealed that GOLPH3L promotes central carbon metabolism in breast cancer by stabilizing the p53 suppressor SERPINE1. CONCLUSIONS: In summary, we discovered a miRNA-GOLPH3L-SERPINE1 pathway that plays important roles in the metabolism of breast cancer and provides new therapeutic targets for human breast cancer.

[Research on application of determination of MMP-13 in osteoarthritis].

Osteoarthritis (OA) is a complex chronic progressive disease attacked by biological and mechanical factors and a result from the anabolic and catabolic imbalance in chondrocyte, subchondral bone and extracellular matrix(ECM). Etiology and pathological of OA are not yet entirely clear. The degradation and destruction of collagen II caused by matrix metalloproteinase -13 (MMP-13) is considered the core factor in the occurrence and development of OA. The research of MMP-13 inhibitor provide ideas and methods for the treatment of OA. In this article,the role and determination of MMP-13 in OA and the development prospect of MMP-13 inhibitor in the treatment of OA research progress were reviewed.

A genomic-scale artificial microRNA library as a tool to investigate the functionally redundant gene space in Arabidopsis.

Traditional forward genetic screens are limited in the identification of homologous genes with overlapping functions. Here, we report the analyses and assembly of genome-wide protein family definitions that comprise the largest estimate for the potentially redundant gene space in Arabidopsis thaliana. On this basis, a computational design of genome-wide family-specific artificial microRNAs (amiRNAs) was performed using high-performance computing resources. The amiRNA designs are searchable online (http://phantomdb.ucsd.edu). A computationally derived library of 22,000 amiRNAs was synthesized in 10 sublibraries of 1505 to 4082 amiRNAs, each targeting defined functional protein classes. For example, 2964 amiRNAs target annotated DNA and RNA binding protein families and 1777 target transporter proteins, and another sublibrary targets proteins of unknown function. To evaluate the potential of an amiRNA-based screen, we tested 122 amiRNAs targeting transcription factor, protein kinase, and protein phosphatase families. Several amiRNA lines showed morphological phenotypes, either comparable to known phenotypes of single and double/triple mutants or caused by overexpression of microRNAs. Moreover, novel morphological and abscisic acid-insensitive seed germination mutants were identified for amiRNAs targeting zinc finger homeodomain transcription factors and mitogen-activated protein kinase kinase kinases, respectively. These resources provide an approach for genome-wide genetic screens of the functionally redundant gene space in Arabidopsis.