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Probiotics in Women's Health: Mechanisms, Benefits, and Potential Applications for Preventing Bacterial Vaginosis and Sexually Transmitted Diseases in Sexual Health Products 益生菌在妇女健康:机制,效益和潜在的应用,以防止细菌性阴道病和性传播疾病的性健康产品。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-17 DOI: 10.1111/apm.70086
Yousef Nami, Anahita Barghi, Mahsa Sadeghi, Tara Farhadi, Sajjad Babaei, Babak Haghshenas

This review summarizes key clinical findings on probiotics in addressing bacterial vaginosis (BV) and sexually transmitted diseases (STDs) in women. Lactobacillus bacteria play a critical role in maintaining a balanced vaginal microbiome by supporting an acidic environment and helping combat conditions like BV, AIDS, maternal group B Streptococcus (GBS), and candidiasis. Probiotics, either alone or combined with antibiotics, have shown promise in promoting microbiome recovery and potentially reducing recovery time. However, their efficacy depends on the strains used and specific conditions, emphasizing the need for further research. Additionally, probiotics can mitigate risks associated with excessive antibiotic use, including antibiotic resistance. The increasing interest in probiotics for women's sexual health has led to the development of specialized products, though identifying superior strains and optimal dosages remains an ongoing challenge. In conclusion, probiotics offer a non-invasive and cost-effective approach to supporting women's health by promoting microbiota balance and enhancing immune function. They offer a promising strategy for managing BV and potentially reducing STD risks. However, further research is necessary to standardize strains, dosages, and application methods in order to achieve consistent and effective outcomes.

本文综述了益生菌治疗女性细菌性阴道病(BV)和性传播疾病(std)的主要临床研究结果。乳酸菌在维持阴道微生物群平衡方面发挥着关键作用,它支持酸性环境,帮助对抗细菌性阴道炎、艾滋病、母体B群链球菌(GBS)和念珠菌病等疾病。益生菌,无论是单独使用还是与抗生素联合使用,都显示出促进微生物群恢复和潜在地缩短恢复时间的希望。然而,它们的效果取决于所使用的菌株和特定条件,强调需要进一步研究。此外,益生菌可以减轻与抗生素过度使用相关的风险,包括抗生素耐药性。对女性性健康益生菌的兴趣日益浓厚,导致了专门产品的开发,尽管确定优质菌株和最佳剂量仍然是一个持续的挑战。总之,益生菌通过促进微生物群平衡和增强免疫功能,为支持女性健康提供了一种非侵入性和成本效益高的方法。它们为管理细菌性阴道炎和潜在地降低性病风险提供了一种很有前途的策略。然而,为了获得一致和有效的结果,需要进一步的研究来规范菌株、剂量和应用方法。
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引用次数: 0
Exploring Eugenol as a Growth and Biofilm Inhibitor in Leptospira interrogans by a Combined Experimental and Computational Approach 丁香酚作为钩端螺旋体生长和生物膜抑制剂的实验与计算研究。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-17 DOI: 10.1111/apm.70088
Elumalai Rajalakshmi, Bavya Chandrasekhar, Elangovan Saranya, Thirumurthy Madhavan, Mohandass Ramya

Leptospira interrogans, known for its association with environmental biofilms, poses significant challenges in managing leptospirosis due to its persistent virulence and resistance to antimicrobial agents. Addressing the biofilms in infection and resistance necessitates novel anti-leptospiral agents and strategies, with bioactive compounds offering better biomolecules to combat leptospiral biofilms. This study investigates the role of eugenol against L. interrogans, which has been unexplored. In this study, we have evaluated the impact of eugenol on the growth and biofilm formation of L. interrogans. Eugenol inhibited 70% of biofilm formation at its MBIC70 (10 mM). These findings were further validated through fluorescence and scanning electron microscopy to assess cell viability and morphological changes. Furthermore, the expression levels of key genes, csrA and lipL32, associated with bacterial growth and biofilm formation, were analyzed using qRT-PCR. To complement these findings, molecular docking, c-DFT, and ADME profiles were performed to investigate the interaction of eugenol with the transpeptidase/penicillin-binding protein. The results strongly correlate with the biological outcomes observed in the experimental studies, supporting the efficacy of eugenol against L. interrogans.

钩端螺旋体以其与环境生物膜的关联而闻名,由于其持续的毒力和对抗菌剂的耐药性,对钩端螺旋体病的管理构成了重大挑战。解决生物膜感染和耐药性问题需要新的抗钩端螺旋体药物和策略,生物活性化合物提供更好的生物分子来对抗钩端螺旋体生物膜。本研究探讨了丁香酚对甜菜芽孢杆菌的作用,这是一个尚未被探索的领域。在本研究中,我们评估了丁香酚对疑问乳杆菌生长和生物膜形成的影响。丁香酚在其MBIC70 (10 mM)下抑制70%的生物膜形成。这些发现通过荧光和扫描电镜进一步验证,以评估细胞活力和形态变化。此外,利用qRT-PCR分析了与细菌生长和生物膜形成相关的关键基因csrA和lipL32的表达水平。为了补充这些发现,我们进行了分子对接、c-DFT和ADME分析,以研究丁香酚与转肽酶/青霉素结合蛋白的相互作用。该结果与实验研究中观察到的生物学结果密切相关,支持丁香酚对疑问乳杆菌的作用。
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引用次数: 0
Targeting Extracellular Polymeric Substances and Multidrug-Resistant Bacteria Biofilms Using Zinc Oxide–Enhanced Chitosan/Polyvinyl Alcohol Nanofibers Deposited on Bacterial Cellulose 利用氧化锌增强壳聚糖/聚乙烯醇纳米纤维沉积在细菌纤维素上的细胞外聚合物和多重耐药细菌生物膜。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-17 DOI: 10.1111/apm.70082
Suman Esakkimuthu, V. S. Ganga, Ashok Arumugam, Sadhasivam Subramaniam

The rapid emergence of antimicrobial resistance, particularly among multidrug-resistant bacteria (MDRB) and biofilm-associated infections, poses a critical public health threat. In this study, a multifunctional nanocomposite with enhanced antibiofilm potential was developed by integrating zinc oxide nanoparticles (ZnO NPs) into a bacterial cellulose (BC)-based scaffold. ZnO NPs, synthesized via the co-precipitation method, displayed uniform spherical morphology and were comprehensively characterized using UV–Vis, FTIR, FE-SEM, EDS, XRD, and DLS analyses. A composite nanofiber matrix was fabricated by electrospinning a chitosan (CS)/polyvinyl alcohol (PVA) blend containing ZnO NPs onto BC, yielding structurally stable BC-PVA-CS-ZnO nanofibers (NFs). Both ZnO NPs and nanofibers exhibited antioxidant activity (30.42% and 34.54%, respectively), and hemocompatibility, confirming their biocompatible nature. Antibacterial studies against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa revealed significant bacterial inhibition, while biofilm assays demonstrated disruption rates of 29.5% (ZnO NPs) and 24.4% (nanofibers), respectively, against P. aeruginosa. The synergistic integration of ZnO with CS/PVA and BC effectively disrupted extracellular polymeric substances (EPS) and suppressed MDR biofilms. Owing to its structural integrity, biodegradability, and tissue compatibility, the engineered nanocomposite demonstrates strong potential as an alternative to conventional antibiotics for wound management and prevention of biofilm-related resistant infections.

抗菌素耐药性的迅速出现,特别是在耐多药细菌(MDRB)和生物膜相关感染中,构成了严重的公共卫生威胁。在这项研究中,通过将氧化锌纳米颗粒(ZnO NPs)整合到细菌纤维素(BC)基支架中,开发了一种具有增强抗生物膜潜力的多功能纳米复合材料。采用共沉淀法合成的ZnO纳米粒子形貌均匀,并通过UV-Vis、FTIR、FE-SEM、EDS、XRD和DLS分析对其进行了综合表征。将含有ZnO纳米粒子的壳聚糖(CS)/聚乙烯醇(PVA)共混物在BC上静电纺丝制备复合纳米纤维基体,得到结构稳定的BC-PVA-CS-ZnO纳米纤维。氧化锌纳米颗粒和纳米纤维均表现出抗氧化活性(分别为30.42%和34.54%)和血液相容性,证实了其生物相容性。对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌的抑菌研究显示,其对细菌有明显的抑制作用,而生物膜实验显示,对铜绿假单胞菌的破坏率分别为29.5% (ZnO NPs)和24.4%(纳米纤维)。ZnO与CS/PVA和BC的协同整合有效地破坏了细胞外聚合物(EPS)并抑制了MDR生物膜。由于其结构完整性、可生物降解性和组织相容性,该工程纳米复合材料在伤口管理和预防生物膜相关耐药感染方面显示出强大的潜力,可替代传统抗生素。
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引用次数: 0
Streptococcus mutans and Cariogenic Biofilms: Mechanisms, Disruption Strategies, and Future Therapeutic Directions 变形链球菌和龋齿生物膜:机制、破坏策略和未来治疗方向。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-17 DOI: 10.1111/apm.70093
Renu Sarah Samson, Anchu Rachel Thomas, Zahida Parveen, Antony Vincent Samrot, Meivelu Moovendhan, Rajalakshmi Deenadhayalan, Ramesh Kumar Varadharajan

Dental caries, a significant global health concern, is intricately linked to the development and persistence of cariogenic biofilms on tooth surfaces. These complex microbial ecosystems orchestrate a multifactorial process of decay, adhering to teeth, producing acids that erode enamel, and exhibiting resistance to traditional therapies. This review delves into the intricate mechanisms of cariogenic biofilm formation and pathogenesis, exploring adhesion, acid production, extracellular polymeric substance (EPS) mediated acid tolerance, and nutrient acquisition within the biofilm. We then explore novel strategies for disrupting these biofilms, including next-generation antimicrobials, anti-adhesion molecules, biofilm-dispersing enzymes, and the potential of probiotics and prebiotics. Finally, the review examines promising future directions in oral disease treatment, highlighting the potential of personalized medicine, biofilm-modifying enzymes and peptides, host modulation strategies, and the development of combination therapies and advanced delivery systems for enhanced biofilm control. Understanding the mechanisms of cariogenic biofilms and exploring innovative treatment strategies could pave the way for more effective prevention and management of dental caries.

龋齿是一个全球性的重大健康问题,它与牙齿表面致龋生物膜的形成和持续存在有着复杂的联系。这些复杂的微生物生态系统协调了一个多因素的腐烂过程,附着在牙齿上,产生腐蚀牙釉质的酸,并表现出对传统疗法的抵抗力。本文从生物膜的粘附、产酸、胞外聚合物质(EPS)介导的酸耐受性以及生物膜内的营养获取等方面深入探讨了龋病生物膜形成和发病的复杂机制。然后,我们探索了破坏这些生物膜的新策略,包括下一代抗菌剂,抗粘附分子,生物膜分散酶,以及益生菌和益生元的潜力。最后,本文回顾了口腔疾病治疗的未来发展方向,强调了个性化医疗、生物膜修饰酶和肽、宿主调节策略、联合疗法的发展和先进的生物膜控制递送系统的潜力。了解蛀牙生物膜的机制,探索创新的治疗策略,可以为更有效地预防和管理蛀牙铺平道路。
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引用次数: 0
Mapping Prevalence, Antimicrobial Resistance, and Biofilm Production of Dairy Farm Associated Coagulase-Positive Staphylococcus aureus From Punjab, India 印度旁遮普省奶牛场相关凝固酶阳性金黄色葡萄球菌的流行、抗菌素耐药性和生物膜生产
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-12 DOI: 10.1111/apm.70089
Deepthi Vijay, Jasbir Singh Bedi, Pankaj Dhaka, Randhir Singh, Anil Kumar Arora, Jatinder Paul Singh Gill

Antimicrobial-resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is an increasing concern in dairy production. Using a One Health approach, this cross-sectional study assessed the prevalence, antimicrobial resistance (AMR) profiles, and biofilm-forming ability of S. aureus from pooled bovine milk, animal handler hand swabs, and herd slurry collected from 405 farms across Punjab, India. The prevalence of coagulase-positive S. aureus was highest in hand swabs (43.7%), followed by milk (30.1%) and slurry (17.5%). Phenotypic resistance varied by source: milk isolates showed the greatest resistance to cefoxitin (37.7%) and penicillin (36.9%); hand swab isolates showed resistance to erythromycin (42.9%) and tetracycline (36.7%); and slurry isolates showed resistance to tetracycline (66.2%) and cefoxitin (59.2%). Multidrug resistance (MDR) was found in 45.9% of milk, 60.5% of hand swabs, and 92.9% of slurry isolates. MRSA was detected in 6.6% of milk, 2.8% of hand swab, and 1.4% of slurry isolates, with SCCmec type V as the most common type. Genotypic screening identified blaZ, mecA, tetK, ermC, and aacA-aphD, with the highest genotype–phenotype concordance for tetracycline resistance. Biofilm assays showed 94.9% of isolates formed biofilms; 28.4% were strong producers. MDR milk isolates showed the highest strong biofilm capacity (39.3%). This study underscores the need for integrated AMR surveillance and improved dairy biosecurity.

耐抗生素金黄色葡萄球菌,包括耐甲氧西林金黄色葡萄球菌(MRSA),在乳制品生产中日益受到关注。采用One Health方法,本横断面研究评估了金黄色葡萄球菌的流行率、抗菌素耐药性(AMR)概况和生物膜形成能力,这些金黄色葡萄球菌来自印度旁遮普省405个农场收集的混合牛奶、动物处理人员的手擦子和牛群的浆液。手拭子中凝固酶阳性金黄色葡萄球菌感染率最高(43.7%),其次是牛奶(30.1%)和浆液(17.5%)。表型耐药来源不同:乳分离株对头孢西丁(37.7%)和青霉素(36.9%)的耐药性最大;手拭子分离株对红霉素(42.9%)和四环素(36.7%)耐药;浆液分离株对四环素(66.2%)和头孢西丁(59.2%)耐药。45.9%的牛奶、60.5%的手拭子和92.9%的浆液分离株存在多药耐药(MDR)。在6.6%的牛奶、2.8%的手拭子和1.4%的浆液分离物中检测到MRSA,其中SCCmec V型是最常见的类型。基因型筛选发现,blaZ、mecA、tetK、ermC和aacA-aphD在四环素耐药基因型-表型一致性最高。生物膜试验显示94.9%的分离菌形成生物膜;28.4%的企业是实力雄厚的生产商。MDR乳分离菌的生物膜容量最高(39.3%)。这项研究强调了进行抗菌素耐药性综合监测和改善奶牛生物安全的必要性。
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引用次数: 0
Targeting Pili-Mediated Interactions to Control Dental Plaque Formation 靶向毛纤毛介导的相互作用控制牙菌斑形成。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-12 DOI: 10.1111/apm.70081
Shivam Kumar Tiwari, A. Thayalan, Vengadesan Krishnan

Dental plaque is a complex microbial biofilm that contributes significantly to the onset of oral diseases and related infections. The initial attachment of primary colonizers to the salivary pellicle, which coats the tooth surface, is a critical first step in plaque development. Primary colonizers use pili on their cell surfaces to facilitate attachment to host surfaces and other bacteria. Pili-mediated adhesion and interbacterial coaggregation promote oral biofilm growth. Recent structural studies of primary colonizers and other oral bacteria have provided new insights into the role of pili in dental plaque formation. Understanding the molecular intricacies of pilus assembly and adhesion paves the way for the development of antiadhesive approaches to control dental plaque formation. Disrupting initial bacterial attachment by targeting pili- and pili-mediated interactions may offer a promising strategy to prevent oral biofilm development and associated infections. This review provides updates on pili and pilus components in oral bacteria, with a focus on the primary colonizers of dental plaque from a structural perspective.

牙菌斑是一种复杂的微生物生物膜,对口腔疾病和相关感染的发生起着重要的作用。牙菌斑最初附着在覆盖牙齿表面的唾液膜上,这是牙菌斑发展的关键第一步。最初的定殖菌利用细胞表面的菌毛来促进与宿主表面和其他细菌的附着。毛纤毛介导的粘附和细菌间共聚集促进口腔生物膜的生长。最近对牙菌斑形成过程中毛菌的结构和其他口腔细菌的研究为毛菌在牙菌斑形成中的作用提供了新的见解。了解菌毛组装和粘附的分子复杂性,为开发控制牙菌斑形成的抗粘附方法铺平了道路。通过靶向毛毛和毛毛介导的相互作用来破坏初始细菌附着可能为预防口腔生物膜发育和相关感染提供了一种有希望的策略。本文综述了口腔菌毛和菌毛成分的最新研究进展,并从结构角度对牙菌斑的主要定植菌进行了综述。
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引用次数: 0
Saliva and Anterior Nasal Samples for Detecting Respiratory Viruses in Children 唾液和前鼻样本检测儿童呼吸道病毒。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-12 DOI: 10.1111/apm.70091
Anu Haaramo, Anu Jääskeläinen, Anne Pitkäranta, Mikael Kuitunen, Enni Sanmark, Johanna Nokso-Koivisto

For detecting respiratory viruses, a nasopharyngeal swab sample for polymerase chain reaction (PCR) assays has been the benchmark. Less discomfort related to sampling is requested especially for children, and thus other sample types have been suggested. We examined anterior nasal samples and saliva samples of 59 pediatric patients with respiratory symptoms and compared the results to nasopharyngeal swab samples. The collection of saliva and anterior nasal samples was tolerated better than nasopharyngeal samples in children. Anterior nasal samples were more accurate than saliva samples in detecting respiratory viruses by a multiplex respiratory panel compared to a reference test (nasopharyngeal swab sample by fourplex PCR), and it seems to be a feasible sample type for detecting respiratory viruses with PCR tests in children with respiratory symptoms.

对于检测呼吸道病毒,鼻咽拭子样本进行聚合酶链反应(PCR)检测一直是基准。特别是对儿童要求较少与抽样有关的不适,因此建议使用其他抽样类型。我们检查了59例有呼吸道症状的儿童患者的前鼻样本和唾液样本,并将结果与鼻咽拭子样本进行了比较。儿童对唾液和前鼻样本的耐受性优于鼻咽样本。与参考测试(鼻咽拭子样本采用四重聚合酶链式反应法)相比,前鼻样本在检测呼吸道病毒方面比唾液样本更准确,这似乎是在有呼吸道症状的儿童中使用聚合酶链式反应检测呼吸道病毒的可行样本类型。
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引用次数: 0
Resurgence of Mycoplasma pneumoniae Infections in the Post-COVID-19 Era: Epidemiology, Therapeutic Challenges, and Mitigation Strategies 后covid -19时代肺炎支原体感染的死灰复燃:流行病学、治疗挑战和缓解策略
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-11 DOI: 10.1111/apm.70092
Ruiying Liu, Wenxia Shao, Qing Ye

This study aims to review recent literature on the delayed re-emergence of Mycoplasma pneumoniae (MP) and to discuss its epidemiological characteristics, treatment strategies, and future research directions for global MP prevention and control. Through a systematic review of the recent relevant literature, the epidemiological changes in MP and the rate of increase in drug resistance during and after the COVID-19 pandemic were analyzed. Moreover, the main treatment strategies for MP, including traditional antibiotics, immunomodulators, and combination therapy, were comprehensively analyzed. The results demonstrated that nonpharmacological interventions (NPIs) implemented during the COVID-19 pandemic exerted a marked reduction in MP detection rates. However, subsequent to the progressive relaxation of NPI measures, a resurgence of MP infections has been observed across multiple global regions, accompanied by an escalating prevalence of antimicrobial resistance—particularly concerning macrolide antibiotics. The investigation further conducted systematic analyses of current therapeutic regimens for MP infection, providing critical evaluations of their respective clinical advantages and limitations in practical application. This study proposes strategies for MP's delayed recirculation control amidst its changing epidemiology and drug resistance, offering a scientific basis and practical suggestions for global MP prevention.

本研究旨在回顾近年来关于肺炎支原体(Mycoplasma pneumoniae, MP)迟发性再发的文献,探讨其流行病学特征、治疗策略以及未来全球MP防控的研究方向。通过系统查阅近期相关文献,分析2019冠状病毒病大流行期间和之后MP的流行病学变化和耐药增长率。综合分析了MP的主要治疗策略,包括传统抗生素、免疫调节剂和联合治疗。结果表明,在COVID-19大流行期间实施的非药物干预措施(npi)显着降低了MP检出率。然而,随着NPI措施的逐步放松,在全球多个地区观察到MP感染的复苏,伴随着抗菌素耐药性的不断上升,特别是大环内酯类抗生素。本研究进一步对目前MP感染的治疗方案进行了系统分析,对其各自的临床优势和实际应用中的局限性进行了批判性评价。本研究提出了MP在流行病学和耐药性变化背景下的延迟再循环控制策略,为全球MP预防提供科学依据和实用建议。
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引用次数: 0
Insights Into NASH-Related Cirrhosis: Clinical and Histopathological Perspectives From Liver Transplant Specimens 洞察nash相关肝硬化:从肝移植标本的临床和组织病理学角度。
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-07 DOI: 10.1111/apm.70080
Neda Soleimani, Zahra Jalalian, Mohammad Hossein Anbardar, Maral Mokhtari, Sahand Mohammadzadeh, Kourosh Kazemi, Seyed Ali Malek-Hosseini, Hamed Nikoupour, Davoud Soleimani, Sadaf Mohajerani, Sima Dehghani

Non-alcoholic fatty liver disease (NAFLD) is a common hepatic disease. In the cirrhotic phase, the characteristic manifestations of non-alcoholic steatohepatitis (NASH) disappear, making a diagnosis challenging. During January 2018 and December 2022, all explanted livers with a pre-transplantation clinical diagnosis of NASH-related cirrhosis were included in this study. The clinical data of the patients, the disease duration prior to transplant, and laboratory data were extracted from documents. Concurrently, the hematoxylin and eosin (H&E) slides and special stains were examined. Among the 2229 liver transplantations, 242 cases (11%) were due to the clinical diagnosis of pure NASH (71% = male, 29% = female). The patients' ages ranged from 28 to 74 years. The criteria for diagnosing NASH, including steatosis, ballooning degeneration, and lobular inflammation, were present in only 66%, 47%, and 3% of cirrhotic livers, respectively. Glassy cytoplasm, glycogenated nuclei, and small cell change were other common histologic features. Diagnosis of NASH in the cirrhotic phase is challenging because the characteristic features of NASH, particularly steatosis, may be non-significant or even completely disappear. In this situation, other histological findings, such as glycogenated nuclei or glassy cytoplasm, may help suggest NASH as a potential diagnosis.

非酒精性脂肪肝(NAFLD)是一种常见的肝脏疾病。在肝硬化阶段,非酒精性脂肪性肝炎(NASH)的特征性表现消失,使诊断具有挑战性。在2018年1月至2022年12月期间,所有移植前临床诊断为nash相关肝硬化的移植肝脏被纳入本研究。从文献中提取患者的临床资料、移植前病程及实验室资料。同时进行苏木精和伊红(H&E)玻片和特殊染色。2229例肝移植中,242例(11%)临床诊断为纯NASH(男性71%,女性29%)。患者年龄28 ~ 74岁。诊断NASH的标准,包括脂肪变性、球囊变性和小叶炎症,分别只存在于66%、47%和3%的肝硬化患者中。玻璃质、糖原核和小细胞改变是其他常见的组织学特征。肝硬化期NASH的诊断具有挑战性,因为NASH的特征,特别是脂肪变性,可能不显著甚至完全消失。在这种情况下,其他组织学发现,如糖原核或玻璃质,可能有助于提示NASH的潜在诊断。
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引用次数: 0
Mesalazine Suppresses Colorectal Cancer Liver Metastasis via the HDAC3/Wnt/β-Catenin Axis Through Downregulating Bacteroides fragilis Abundance 美沙嗪通过下调脆弱拟杆菌丰度,通过HDAC3/Wnt/β-Catenin轴抑制结直肠癌肝转移
IF 2.6 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-11-07 DOI: 10.1111/apm.70078
Zhou Yu, Yiwen Li, Jianping Wang

Colorectal cancer (CRC) is characterized by high recurrence and metastasis, resulting in low patient survival. Dysbiosis of intestinal flora increases CRC metastasis risk. Mesalazine, an anti-inflammatory drug with proven antitumor activity, is commonly used to treat CRC in patients with inflammatory bowel disease, but whether it mediates CRC hepatic metastasis by affecting key flora is unknown. An animal model of CRC liver metastasis was established by injecting HCT116 cells into the spleens of mice and treated with mesalazine. Mouse feces were collected for 16S rRNA sequencing to analyze the abundance of intestinal flora. In vitro experiments demonstrated that mesalazine inhibited proliferation, migration, and invasion of CRC by modulating Bacteroides fragilis. Rescue experiments validated molecular mechanisms. Mesalazine inhibited CRC hepatic metastasis and reduced the abundance of Bacteroides fragilis in the feces of CRC hepatic metastatic mice by 16S rRNA sequencing analysis. In vitro experiments showed that mesalazine inhibited proliferation, migration, and invasion of CRC by affecting Bacteroides fragilis, mainly through the histone deacetylase 3 (HDAC3)/Wingless/Int/Beta-catenin (Wnt/β-catenin) axis. The study elucidated the mechanism by which mesalazine inhibited CRC liver metastasis through the HDAC3/Wnt/β-catenin axis by affecting the abundance of Bacteroides fragilis, which provided a new idea for CRC treatment.

结直肠癌(CRC)的特点是高复发和转移,导致患者生存率低。肠道菌群失调增加结直肠癌转移风险。美沙拉嗪是一种具有抗肿瘤活性的抗炎药物,常用于治疗炎症性肠病患者的结直肠癌,但是否通过影响关键菌群介导结直肠癌肝转移尚不清楚。采用小鼠脾内注射HCT116细胞并给予美沙拉嗪处理,建立结直肠癌肝转移动物模型。收集小鼠粪便进行16S rRNA测序,分析肠道菌群丰度。体外实验表明,美沙拉嗪通过调节脆弱拟杆菌抑制结直肠癌的增殖、迁移和侵袭。救援实验验证了分子机制。通过16S rRNA测序分析,美沙拉嗪抑制结直肠癌肝转移,降低结直肠癌肝转移小鼠粪便中脆弱拟杆菌的丰度。体外实验表明,美萨拉嗪通过影响脆弱拟杆菌(Bacteroides fragilis),主要通过组蛋白去乙酰化酶3 (HDAC3)/Wingless/Int/ β-catenin (Wnt/β-catenin)轴,抑制结直肠癌的增殖、迁移和侵袭。本研究阐明了美萨拉嗪通过HDAC3/Wnt/β-catenin轴通过影响脆弱拟杆菌(Bacteroides fragilis)丰度抑制结直肠癌肝转移的机制,为结直肠癌治疗提供了新的思路。
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