Objective: Chemotherapy failure derived from drug resistance is the most important reason causing the recurrence in colorectal cancer patients. Therefore, it is necessary to shed light on the mechanism of chemotherapy resistance in colorectal cancer patients. Methods: We looked into the contribution of Fusobacterium nucleatum and ANO1 to chemoresistance in the human colorectal carcinoma cell lines. We silence and overexpress ANO1 in HCT116 and HT29 cells with lentivirus and siRNA knockdown technique in the absence or presence of F. nucleatum, oxaliplatin or 5-fluorouracil (5-FU). ANO1, p-pg, cleaved PARP, cleaved caspase-3, and EGFR expression was measured by Western blot. Cell apoptosis was measured by flow cytometry. Results: We found that F. nucleatum promoted ANO1 expression on colon cancer cells. Moreover, ANO1 prevent colon cancer apoptosis from oxaliplatin and 5-FU. Additionally, knockdown ANO1 expression could block F. nucleatum protective effects and increase the apoptosis effects induced by oxaliplatin and 5-FU. Therefore, F. nucleatum might be biologically involved in the development of colon cancer chemoresistance via ANO1 pathway. Conclusions: Taken together, our findings provide a valuable insight into clinical management and therapy, which may ameliorate colorectal cancer patient outcomes.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant public health problem. This study investigated the antimicrobial properties and mechanisms of berberine (BBR), a plant alkaloid, against MRSA, evaluating its potential to enhance antibiotic therapy. Berberine only demonstrated variable but significant inhibitory effects on 50 clinical MRSA strains. When combined with antibiotics, synergistic effects were observed only with amikacin in 6 of the 50 MRSA strains. BBR disrupted MRSA cell wall integrity, leading to leakage of cellular contents. Network pharmacology analysis revealed that BBR targets multiple pathways essential for bacterial survival. The study confirmed the potent antimicrobial activity of berberine against MRSA and its capability to act synergistically with traditional antibiotics. Berberine’s impact on cell wall integrity and bacterial survival pathways highlights its potential as an adjunct therapy in MRSA treatment.

Hospital and community-acquired infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) have emerged as a significant public health challenge, highlighting the urgent need for novel antibiotics. In response, the antibacterial properties of natural products derived from traditional plants are being investigated as potential treatments for multidrug resistance. This study demonstrates the potent antibacterialimoact of Berberine (BBR), a compound derived from traditional Chinese medicine, against the community-associated MRSA (CA-MRSA) strain USA300 LAC. Through a comprehensive series of in vitro antibacterial experiments and gene-level investigations, we discovered that BBR compromises the integrity of the USA300 LAC cell wall structure. This mechanism of action is likely attributed to the inhibition of the tarO gene, which encodes a critical enzyme in the initial stage of wall teichoic acid (WTA) biosynthesis, thereby suppressing WTA synthesis, an essential component of the cell wall. Additionally, BBR upregulates the expression of lytic enzymes LytM and SsaA, resulting in accelerated hydrolysis of peptidoglycan, a major structural element of the cell wall. This disruption ultimately leads to the destruction of the USA300 LAC cell wall. Moreover, combined antibacterial assays reveal that BBR synergistically enhances the antibacterial effect of Oxacillin against USA300 LAC. Overall, our findings elucidate the antibacterial mechanism of BBR, a traditional Chinese medicine monomer, against MRSA and highlight its promising potential for clinical application in the treatment of MRSA.

Background: Human papillomavirus (HPV) can cause various gynecological diseases, create a long-term inflammatory immune microenvironment, and induce the occurrence of cervical tumors. However, the prevalence of HPV is species-specific in different eras or in different countries and regions. This paper aimed to investigate the characteristics of HPV infection in the Xuhui District, Shanghai City, China. Methods: We collected HPV data from 6,760 female testers, focusing on the younger population for data analysis. We focused more on the HPV subtypes to which young women were susceptible, performed t-Distributed Stochastic Neighbor Embedding (TSNE) analysis to screen for characteristic subtypes, and compared the prevalent subtypes lacking effective vaccine protection. Results: HPV infection exhibited a trend of affecting a younger population, and eight subtypes were more likely to occur in young people. HPV43, 51, 53, and 59 showed a higher incidence and lacked vaccine protection. We performed TSNE dimensionality reduction analysis to organize the HPV data. The results indicated that HPV16, 18, and 51 are characteristic subtypes in the younger population. The Thinprep cytologic test (TCT) also revealed that the infection with HPV43, 51, 53, and 59 also triggers significant pathological phenotypes. Conclusions: HPV51 is a subtype that occurs more frequently in young women, can induce a variety of significant pathological features, and lacks effective vaccine protection. This study inspires us to take measures to deal with HPV rejuvenation and conduct research on vaccines for specific HPV subtypes.

In China, Cervical cancer is one of the common malignant tumors in females, and high-risk human papillomavirus (HR-HPV) infection is one of its main causative factors. However, human papillomavirus (HPV) infection rates may vary significantly among patients of different ages and HPV subtypes. This study aims to provide insights into developing cervical cancer screening strategies and selecting HPV vaccine antigen targets in the area. A retrospective analysis was conducted on the HPV testing results of 47,423 women from January 2017 to April 2023 at the Clinical Laboratory of the Eighth People’s Hospital in Shanghai. HPV DNA genotyping was performed using real-time quantitative polymerase chain reaction (PCR) in the molecular laboratory. Statistical analysis was carried out using GraphPad Prism 8.0.1 software. Binomial distribution analysis was used to calculate the 95% confidence intervals (95% CI), and the chi-square test was employed to compare categorical variables among different age groups, with a p-value of less than 0.05 indicating statistical significance. Among the 47,423 cervical HPV DNA test results, the overall infection rate was 18.9%, with single infections accounting for 13.93%, dual infections for 3.47%, and multiple infections for 1.5%. The age-specific prevalence of HPV infection exhibited a “U”-shaped curve, with the highest infection rates observed in the age groups under 30 and between 50 and 59 years. The five most common HR-HPV subtypes in Xuhui District were types 16, 39, 51, 52, 56, and 58 (accounting for 10.3%, 7%, 8%, 20.3%, 6%, and 12%, respectively), with type 52 showing the highest infection rate. The prevalence of moderate/severe HPV infection rates in the HPV 59, HPV 33, and HPV 35 gene subtypes increased over time, highlighting the importance of monitoring these subtypes. This study identified the primary HR-HPV genotypes prevalent among females in Xuhui District, Shanghai, and explored correlations between age, genotype, and HPV infection rates. While the findings provide a basis for recommending HPV screening for younger and older age groups, further studies integrating clinical outcomes such as cytological and pathological results are necessary to substantiate these conclusions and refine screening strategies. Due to variations in HPV trends globally and regional differences in genotypes, epidemiological analysis of HPV can accurately and visually reflect the distribution of specific HPV genotypes in a particular area, thereby aiding in the development of regional cervical cancer screening strategies and the selection of HPV vaccine antigen targets.

ΦC31 integrase, a site-specific recombinase, can efficiently target attB-bearing transgenes to endogenous pseudo attP sites within mammalian genomes. The sequence features of endogenous binding sites will help us to fully understand the site-specific recognition function by ΦC31 integrase. The present study was aimed to uncover the global map of ΦC31 integrase binding sites in bovine cells and analysis the features of these binding sites by comprehensive bioinformatics methods. In this study, we constructed a ChIP-seq method that can be used to uncover the global binding sites by phiC31 integrase. 6740 potential ΦC31 integrase binding sites were identified. A sequence motif was found that contains inverted repeats and has similarities to wild-type attP site. Using REPEATMASKER, we identified a total of 20,183 repeat-regions distributed in 50 repeat types for the 6740 binding sites. These sites enriched in “regulation of GTPase activity” of in the GO category of biological process and KEGG pathway of signal transmembrane transporter activity. This study is the first time to uncover the global map of binding sites for ΦC31 integrase using ChIP-sequencing method and analysis the features of these binding sites. This method will help us to fully understand the mechanism of the site-specific integration function by phiC31 integrase and will potentially boost its genetic manipulations in both gene therapy and generation of transgenic animals.