Biology Direct最新文献

{"title":"ALKBH5 activates CEP55 transcription through m6A demethylation in FOXP2 mRNA and expedites cell cycle entry and EMT in ovarian cancer.","authors":"Junhui Yu, Xing Chen, Xiaoxiao Ding, Kang Lin, Tianxin Zhang, Kai Wang","doi":"10.1186/s13062-024-00551-5","DOIUrl":"10.1186/s13062-024-00551-5","url":null,"abstract":"<p><strong>Background: </strong>Centrosomal protein of 55 kDa (CEP55) overexpression has been linked to tumor stage, aggressiveness of the tumor, poor prognosis, and metastasis. This study aims to elucidate the action of CEP55 in ovarian cancer (OC) and the regulation by the alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5)/Forkhead box protein P2 (FOXP2) axis.</p><p><strong>Methods: </strong>Differentially expressed genes in OC were identified using in silico identification, followed by prognostic value assessment. Lentiviral vectors were constructed to downregulate CEP55 in OC cells, and colony formation, EdU, TUNEL, flow cytometry, Transwell assays, and Phalloidin staining were conducted. Transcription factors regulating CEP55 were predicted and verified, and rescue experiments were performed. The effect of ALKBH5-mediated demethylation on FOXP2 mRNA stability and OC cell cycle and EMT were analyzed.</p><p><strong>Results: </strong>High expression of CEP55 in OC was linked to unsatisfactory prognosis of patients. Knockdown of CEP55 repressed proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) while inducing apoptosis and cell cycle arrest in OC cells. FOXP2 bound to the promoter of CEP55 to repress CEP55 transcription. FOXP2 regulated transcriptional repression of CEP55 to impede the malignant progression of OC and inhibit tumor metastasis. ALKBH5-mediated demethylation modification induced mRNA degradation of FOXP2. Knockdown of ALKBH5 induced cell cycle arrest and inhibited EMT in OC cells.</p><p><strong>Conclusions: </strong>ALKBH5 hinders FOXP2-mediated transcriptional repression of CEP55 to promote the malignant progression of OC via cell cycle and EMT.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"105"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FXR1 associates with and degrades PDZK1IP1 and ATOH8 mRNAs and promotes esophageal cancer progression.","authors":"Faiz Ali Khan, Dalia Fouad, Farid S Ataya, Na Fang, Jingcheng Dong, Shaoping Ji","doi":"10.1186/s13062-024-00553-3","DOIUrl":"10.1186/s13062-024-00553-3","url":null,"abstract":"<p><strong>Background: </strong>The growing body of evidence suggests that RNA-binding proteins (RBPs) have an important function in cancer biology. This research characterizes the expression status of fragile X-related protein 1 (FXR1) in esophageal cancer (ESCA) cell lines and understands its mechanistic importance in ESCA tumor biology.</p><p><strong>Methods: </strong>The role of FXR1, PDZK1IP1, and ATOH8 in the malignant biological behaviors of ESCA cells was investigated using in-vitro and in-vivo experiments.</p><p><strong>Results: </strong>FXR1 was aberrantly overexpressed at both the transcript and protein levels in ESCA cells. Deficiency of FXR1 in ESCA cells was associated with decreased cell proliferation, viability and compromised cell migration compared to the control group. In addition, the inhibition of FXR1 leads to the promotion of apoptosis and cell cycle arrest in ESCA cells. Furthermore, FXR1 knockdown stabilizes senescence markers, promoting cellular senescence and decreasing cancer growth. Mechanistically, FXR1 negatively regulated PDZK1IP1 or ATOH8 transcripts by promoting mRNA degradation via direct interaction with its 3'UTR. PDZK1IP1 or ATOH8 overexpression predominantly inhibited the tumor-promotive phenotype in FXR1-overexpressed cells. Furthermore, FXR1 inhibition and PDZK1IP1 or ATOH8 overexpression in combination with FXR1-overexpressed cells significantly decreased xenograft tumor formation and enhanced nude mouse survival without causing apparent toxicity (P < 0.01). In the FXR1 knockdown group, the tumor weight of mice decreased by 80% compared to the control group (p < 0.01).</p><p><strong>Conclusions: </strong>Our results demonstrate FXR1's oncogenic involvement in ESCA cell lines, suggesting that FXR1 may be implicated in ESCA development by regulating the stability of PDZK1IP1 and ATOH8 mRNAs. For the first time, our findings emphasize the importance of FXR1-PDZK1IP1 and -ATOH8 functional modules in the development of ESCA, which might have potential diagnostic or therapeutic implications.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"104"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF19A inhibits bladder cancer progression by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway.","authors":"Hao Deng, Guanghai Ji, Jun Ma, Jun Cai, Shaoping Cheng, Fan Cheng","doi":"10.1186/s13062-024-00562-2","DOIUrl":"10.1186/s13062-024-00562-2","url":null,"abstract":"<p><strong>Background: </strong>The role of the RING finger protein superfamily in carcinogenesis has been widely studied, but one member of this family, RNF19A, has not yet been thoroughly explored in bladder cancer (BCa).</p><p><strong>Methods: </strong>The expression levels of RNF19A in BCa samples and cell lines were analysed through data mining of public resources and further experiments. BCa cells in which RNF19A was stably overexpressed or knocked down were generated through lentivirus infection. The effects of RNF19A on cell proliferation, migration, and invasion were explored by performing a series of in vitro experiments, including CCK-8, colony formation, wound healing, and Transwell invasion assays. Using bioinformatics methods and multiple experiments, including western blot, qRT‒PCR, immunoprecipitation, cycloheximide, ubiquitination, and rescue assays, the mechanism underlying the effect of RNF19A on the progression of BCa was investigated.</p><p><strong>Results: </strong>Here, we found that RNF19A expression was reduced in BCa samples and cell lines and that lower RNF19A expression predicted shorter overall survival of BCa patients. Functionally, forced expression of RNF19A suppressed BCa cell proliferation, migration, and invasion by inactivating the AKT/mTOR signalling pathway, whereas silencing RNF19A had the opposite effects. Mechanistically, RNF19A could directly interact with ILK and promote its ubiquitination and degradation. Rescue experiments revealed that forced ILK expression partially rescued the decreased phosphorylation of AKT, mTOR, and S6K1 caused by RNF19A overexpression and that the increased levels of the p-AKT, p-mTOR, and p-S6K1 proteins induced by RNF19A knockdown were eliminated after silencing ILK. Similarly, the effects of RNF19A overexpression or knockdown on the phenotypes of cell proliferation, migration, and invasion could also be restored by forced or decreased ILK expression.</p><p><strong>Conclusions: </strong>RNF19A suppressed the proliferation, migration, and invasion abilities of BCa cells by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway. RNF19A might be a potential prognostic biomarker and promising therapeutic target for BCa.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"102"},"PeriodicalIF":5.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of potential natural therapeutics targeting cell wall biosynthesis in multidrug-resistant Enterococcus faecalis: a computational perspective.","authors":"Km Rakhi, Monika Jain, Amit Kumar Singh, Mohd Sajid Ali, Hamad A Al-Lohedan, Jayaraman Muthukumaran","doi":"10.1186/s13062-024-00538-2","DOIUrl":"10.1186/s13062-024-00538-2","url":null,"abstract":"<p><strong>Background: </strong>Identifying therapeutic inhibitors of crucial enzymes involved in the peptidoglycan biosynthesis pathway is pivotal for developing new treatments against multidrug-resistant Enterococcus faecalis V583. MurM, an essential enzyme in this pathway, plays a significant role in the bacterium's cell wall synthesis, making it an attractive druggable target for novel antimicrobial strategies. This study explored the potential of natural compounds as inhibitors of MurM, aiming to discover promising drug candidates that could serve as the foundation for future therapeutic development.</p><p><strong>Methods: </strong>The three-dimensional structure of MurM was predicted, optimized, and its binding pocket was analyzed by comparing it with related structures. Over 4,70,000 natural compounds from the COCONUT database were subjected to virtual high-throughput screening (vHTS). The top lead candidates were selected based on their Lipinski's profile, ADME profile, toxicity profile, estimated binding free energy (ΔG) and estimated inhibition constant (Ki). Interaction pattern analysis was used to evaluate the non-covalent interactions between the inhibitors and key residues in MurM's binding pocket. Molecular dynamics simulations were performed over 300 ns to assess the structural stability and impact of these inhibitors on MurM's enzyme.</p><p><strong>Results: </strong>Three lead compounds-CNP0056520, CNP0126952, and CNP0248480-were identified and prioritized with estimated ΔG ranging from - 9.35 to -7.9 kcal/mol. Molecular dynamics simulations revealed minimal impact on MurM's overall structure and dynamics, with the candidate inhibitors forming stable protein-ligand complexes. These interactions were supported by several non-covalent interactions between the candidate inhibitors and key residues within MurM's binding pocket.</p><p><strong>Conclusion: </strong>These findings suggest that the identified natural product candidates could serve as promising inhibitors of MurM, potentially leading to novel therapeutics targeting cell wall biosynthesis in multidrug-resistant E. faecalis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"101"},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of gut microbiota dynamics in an Alzheimer's disease mouse model through clade-specific marker-based analysis of shotgun metagenomic data.","authors":"Francesco Favero, Angela Re, Mohammed Salim Dason, Teresa Gravina, Mara Gagliardi, Marta Mellai, Marco Corazzari, Davide Corà","doi":"10.1186/s13062-024-00541-7","DOIUrl":"10.1186/s13062-024-00541-7","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder significantly impairing cognitive faculties, memory, and physical abilities. To characterize the modulation of the gut microbiota in an in vivo AD model, we performed shotgun metagenomics sequencing on 3xTgAD mice at key time points (i.e., 2, 6, and 12 months) of AD progression. Fecal samples from both 3xTgAD and wild-type mice were collected, DNA extracted, and sequenced. Quantitative taxon abundance assessment using MetaPhlAn 4 ensured precise microbial community representation. The analysis focused on species-level genome bins (SGBs) including both known and unknown SGBs (kSGBs and uSGBs, respectively) and also comprised higher taxonomic categories such as family-level genome bins (FGBs), class-level genome bins (CGBs), and order-level genome bins (OGBs). Our bioinformatic results pinpointed the presence of extensive gut microbial diversity in AD mice and showed that the largest proportion of AD- and aging-associated microbiome changes in 3xTgAD mice concern SGBs that belong to the Bacteroidota and Firmicutes phyla, along with a large set of uncharacterized SGBs. Our findings emphasize the need for further advanced bioinformatic studies for accurate classification and functional analysis of these elusive microbial species in relation to their potential bridging role in the gut-brain axis and AD pathogenesis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"100"},"PeriodicalIF":5.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfidptosis-related subtype and prognostic signature in prostate cancer.","authors":"Zhen Kang, Zheng-Hua Wan, Rui-Cheng Gao, Dong-Ning Chen, Qing-Shui Zheng, Xue-Yi Xue, Ning Xu, Yong Wei","doi":"10.1186/s13062-024-00544-4","DOIUrl":"10.1186/s13062-024-00544-4","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear.</p><p><strong>Methods: </strong>Firstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot.</p><p><strong>Results: </strong>Although SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients.</p><p><strong>Conclusion: </strong>This study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"97"},"PeriodicalIF":5.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the impact of MreB on the morphology and pathogenicity of the aquatic pathogen Spiroplasma eriocheiris.","authors":"Rong Li, Xiaohui Cao, Jiaxin Chen, Tingting He, Yan Zhang, Wen Wang, Yaqi Wang, Yifei Wang, Yanyan Qiu, Mengji Xie, Kailin Shi, Yuhua Xu, Siyuan Zhang, Peng Liu","doi":"10.1186/s13062-024-00537-3","DOIUrl":"10.1186/s13062-024-00537-3","url":null,"abstract":"<p><strong>Background: </strong>Spiroplasma eriocheiris has been proved to be a pathogen causing tremor disease of Eriocheir sinensis, it is also infectious to other aquatic crustaceans, resulting in a serious threat on the sustainable development of the aquaculture industry. S. eriocheiris is a helical-shaped microbe without a cell wall, and its motility is related to the cytoskeleton protein MreB which belongs to the actin superfamily and has five MreB homologs.</p><p><strong>Results: </strong>In this study, we purified MreB3, MreB4 and MreB5, and successfully prepared monoclonal antibodies. After S. eriocheiris treated with actin stabilizator Phalloidin and inhibitors A22, we found that Phalloidin and A22 affect the S. eriocheiris morphology by altering MreB expression. We confirmed that the ability of S. eriocheiris to invade E. sinensis was increased after treatment with Phalloidin, including that the morphology of E. sinensis blood lymphocytes was deteriorated, blood lymphocytes viability was decreased, peroxidase activity and cell necrosis were increased. On the contrary, the pathogenicity of S. eriocheiris decreased after treatment with A22.</p><p><strong>Conclusions: </strong>Our findings suggest that the MreB protein in S. eriocheiris plays a crucial role in its morphology and pathogenicity, providing new insights into potential strategies for the prevention and control of S. eriocheiris infections.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"98"},"PeriodicalIF":5.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of renal ischemia-reperfusion injury and tubular epithelial cell ferroptosis by pparγ m6a methylation: mechanisms and therapeutic implications.","authors":"Wei Liu, Ziqing Xiong, Tianmei Fu, Juan Yang, Juan Zou, Yize Wu, Linju Kuang, Qian Wang, Song Li, Aiping Le","doi":"10.1186/s13062-024-00515-9","DOIUrl":"10.1186/s13062-024-00515-9","url":null,"abstract":"<p><p>This study aimed to elucidate the role and underlying mechanisms of Peroxisome proliferator-activated receptor gamma (PPARγ) and its m6A methylation in renal ischemia-reperfusion (I/R) injury and ferroptosis of tubular epithelial cells (TECs). High-throughput transcriptome sequencing was performed on renal tissue samples from I/R injury models and sham-operated mice, complemented by in vivo and in vitro experiments focusing on the PPARγ activator Rosiglitazone and the manipulation of METTL14 and IGF2BP2 expression. Key evaluations included renal injury assessment, ferroptosis indicator measurement, and m6A methylation analysis of PPARγ. Our findings highlight the critical role of the PPARγ pathway and ferroptosis in renal I/R injury, with Rosiglitazone ameliorating renal damage and TEC ferroptosis. METTL14-mediated m6A methylation of PPARγ, dependent on IGF2BP2, emerged as a pivotal regulator of PPARγ expression, renal injury, and ferroptosis. This study reveals that PPARγ m6A methylation, orchestrated by METTL14 through an IGF2BP2-dependent mechanism, plays a crucial role in mitigating renal I/R injury and TEC ferroptosis. These insights offer promising avenues for therapeutic strategies targeting acute kidney injury.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"99"},"PeriodicalIF":5.7,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex antimicrobial activities of the self-assembled amphiphilic polypeptide β nanofiber KF-5 against vaginal pathogens.","authors":"Ling Fang, Tiancheng Yang, Haojue Wang, Jun Cao","doi":"10.1186/s13062-024-00546-2","DOIUrl":"https://doi.org/10.1186/s13062-024-00546-2","url":null,"abstract":"<p><strong>Background: </strong>Vaginal infections caused by multidrug-resistant pathogens such as Candida albicans and Gardnerella spp. represent a significant health challenge. Current treatments often fail because of resistance and toxicity. This study aimed to synthesize and characterize a novel amphiphilic polypeptide, KF-5, and evaluate its antibacterial and antifungal activities, biocompatibility, and potential mechanisms of action.</p><p><strong>Results: </strong>The KF-5 peptide was synthesized via solid-phase peptide synthesis and self-assembled into nanostructures with filamentous and hydrogel-like configurations. Characterization by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) confirmed the unique nanostructural properties of KF-5. KF-5 (125, 250, or 500 µg/ml) demonstrated potent antibacterial and antifungal activities, with significant inhibitory effects on drug-resistant Candida albicans and Gardnerella spp. (P < 0.05). In vitro assays revealed that 500 µg/ml KF-5 disrupted microbial cell membranes, increased membrane permeability, and induced lipid oxidation, leading to cell death (P < 0.05). Cytotoxicity tests revealed minimal toxicity in human vaginal epithelial cells, keratinocytes, and macrophages, with over 95% viability at high concentrations. Molecular dynamics simulations indicated that KF-5 interacts with phospholipid bilayers through electrostatic interactions, causing membrane disruption. In vivo studies using a mouse model of vaginal infection revealed that 0.5, 1, and 2 mg/ml KF-5 significantly reduced fungal burden and inflammation, and histological analysis confirmed the restoration of vaginal mucosal integrity (P < 0.01). Compared with conventional antifungal treatments such as miconazole, KF-5 exhibited superior efficacy (P < 0.01).</p><p><strong>Conclusions: </strong>KF-5 demonstrates significant potential as a safe and effective antimicrobial agent for treating vaginal infections. Its ability to disrupt microbial membranes while maintaining biocompatibility with human cells highlights its potential for clinical application. These findings provide a foundation for further development of KF-5 as a therapeutic option for combating drug-resistant infections.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"96"},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIR194-2HG, a miRNA host gene activated by HNF4A, inhibits gastric cancer by regulating microRNA biogenesis.","authors":"Hong Cao, Zidi Wang, Qiwei Guo, Shanshan Qin, Dandan Li","doi":"10.1186/s13062-024-00549-z","DOIUrl":"https://doi.org/10.1186/s13062-024-00549-z","url":null,"abstract":"<p><strong>Background: </strong>MicroRNA host gene (MIRHG) lncRNA is a particular lncRNA subclass that can perform both typical and atypical lncRNA functions. The biological function of MIRHG lncRNA MIR194-2HG in cancer is poorly understood.</p><p><strong>Methods: </strong>Loss-of-function studies were performed in vivo and in vitro to reveal the biological function of MIR194-2HG in GC. MicroRNA PCR array, northern blotting, RNA sequencing, chromatin immunoprecipitation, and rescue assays were conducted to uncover the molecular mechanism of MIR194-2HG.</p><p><strong>Results: </strong>In this study, we reported an atypical lncRNA function of MIR194-2HG in GC. MIR194-2HG downregulation was clinically associated with malignant progression and poor prognosis in GC. Functional assays confirmed that MIR194-2HG knockdown significantly promoted GC proliferation and metastasis in vitro and in vivo. Mechanismically, MIR194-2HG was required for the biogenesis of miR-194 and miR-192, which were reported to be tumor-suppressor genes in GC. Moreover, hepatocyte nuclear factor HNF4A directly activated the transcription of MIR194-2HG and its derived miR-194 and miR-192. Meanwhile, BTF3L4 was proved to be a common target gene of miR-192 and miR-194. Rescue assay further confirmed that MIR194-2HG knockdown promotes GC progression through maintaining BTF3L4 overexpression in a miR-194/192-dependent manner.</p><p><strong>Conclusion: </strong>The dysregulated MIR194-2HG/BTF3L4 axis is responsible for GC progression. Targeting HNF4A to inhibit miR-192/194 expression may be a promising strategy for overcoming GC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"19 1","pages":"95"},"PeriodicalIF":5.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}