ApmisPub Date : 2024-12-01Epub Date: 2023-11-08DOI: 10.1111/apm.13356
Jiatian Ye, Xiaorong Qi
{"title":"Vaginal microecology and its role in human papillomavirus infection and human papillomavirus associated cervical lesions.","authors":"Jiatian Ye, Xiaorong Qi","doi":"10.1111/apm.13356","DOIUrl":"10.1111/apm.13356","url":null,"abstract":"<p><p>The vaginal microecology comprises the vaginal microbiome, immune microenvironment, vaginal anatomy, and the cervicovaginal fluid, which is rich in metabolites, enzymes, and cytokines. Investigating its role in the female reproductive system holds paramount significance. The advent of next-generation sequencing enabled a more profound investigation into the structure of the vaginal microbial community in relation to the female reproductive system. Human papillomavirus infection is prevalent among women of reproductive age, and persistent oncogenic HPV infection is widely recognized as a factor associated with cervical cancer. Extensive previous research has demonstrated that dysbiosis of vaginal microbiota characterized by a reduction in Lactobacillus species, heightens susceptivity to HPV infection, consequently contributing to persistent HPV infection and the progression of cervical lesion. Likewise, HPV infection can exacerbate dysbiosis. This review aims to provide a comprehensive summary of current literatures and to elucidate potential mechanisms underlying the interaction between vaginal microecology and HPV infection, with the intention of offering valuable insights for future clinical interventions.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"928-947"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApmisPub Date : 2024-12-01Epub Date: 2024-10-06DOI: 10.1111/apm.13473
Jing Kong, Juan Yang, Cong He, Bingduo Zhou, Shengquan Fang, Manisha Salinas, Arya B Mohabbat, Brent A Bauer, Xiaosu Wang
{"title":"Regulation of endotoxemia through the gut microbiota: The role of the Mediterranean diet and its components.","authors":"Jing Kong, Juan Yang, Cong He, Bingduo Zhou, Shengquan Fang, Manisha Salinas, Arya B Mohabbat, Brent A Bauer, Xiaosu Wang","doi":"10.1111/apm.13473","DOIUrl":"10.1111/apm.13473","url":null,"abstract":"<p><p>Endotoxemia is closely related to many diseases. As the largest endotoxin reservoir in the human body, the gut microbiota should be a key target for alleviating endotoxemia. The intestinal microbiota is believed to cause endotoxemia directly or indirectly by modifying the intestinal barrier function through dysbiosis, changing intestinal mucosal permeability and bacterial translocation. Diet is known to be the main environmental factor affecting the intestinal microbiota, and different diets and food components have a large impact on the gut microbiota. The Mediterranean diet, which received much attention in recent years, is believed to be able to regulate the gut microbiota, thereby maintaining the function of the intestinal barrier and alleviating endotoxemia. In this review, we focus on the relationship between the gut microbiota and endotoxemia, and how the Mediterranean dietary (MD) pattern can interfere with endotoxemia through the gut microbiota.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"948-955"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApmisPub Date : 2024-12-01Epub Date: 2024-01-29DOI: 10.1111/apm.13381
Peter Østrup Jensen, Pernille Olsen, Arnold Matovu Dungu, Gertrud Baunbæk Egelund, Andreas Vestergaard Jensen, Pernille Ravn, Birgitte Lindegaard, Frederik Boëtius Hertz, Thomas Bjarnsholt, Daniel Faurholt-Jepsen, Mette Kolpen
{"title":"Bacterial aerobic respiration is a major consumer of oxygen in sputum from patients with acute lower respiratory tract infection.","authors":"Peter Østrup Jensen, Pernille Olsen, Arnold Matovu Dungu, Gertrud Baunbæk Egelund, Andreas Vestergaard Jensen, Pernille Ravn, Birgitte Lindegaard, Frederik Boëtius Hertz, Thomas Bjarnsholt, Daniel Faurholt-Jepsen, Mette Kolpen","doi":"10.1111/apm.13381","DOIUrl":"10.1111/apm.13381","url":null,"abstract":"<p><p>Bacterial aerobic respiration may determine the outcome of antibiotic treatment in experimental settings, but the clinical relevance of bacterial aerobic respiration for the outcome of antibiotic treatment has not been tested. Therefore, we hypothesized that bacterial aerobic respiration is higher in sputum from patients with acute lower respiratory tract infections (aLRTI), than in sputum from patients with chronic LRTI (cLRTI), where the bacteria persist despite antibiotic treatment. The bacterial aerobic respiration was determined according to the dynamics of the oxygen (O<sub>2</sub>) concentration in sputum from aLRTI patients (n = 52). This result was evaluated by comparison to previously published data from patients with cLRTI. O<sub>2</sub> consumption resulting in anoxic zones was more frequent in sputum with detected bacterial pathogens. The bacterial aerobic respiration in aLRTI sputum approximated 55% of the total O<sub>2</sub> consumption, which was significantly higher than previously published for cLRTI. The bacterial aerobic respiration in sputum was higher in aLRTI patients than previously seen in cLRTI patients, indicating the presence of bacteria with a sensitive physiology in aLRTI. These variations in bacterial physiology between aLRTI patients and cLRTI patients may contribute the huge difference in treatment success between the two patient groups.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"1078-1085"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-PD-L1 chimeric antigen receptor natural killer cell: Characterization and functional analysis.","authors":"Mahsa Yazdanpanah-Samani, Amin Ramezani, Abdolkarim Sheikhi, Zohreh Mostafavi-Pour, Nasrollah Erfani","doi":"10.1111/apm.13471","DOIUrl":"10.1111/apm.13471","url":null,"abstract":"<p><p>Like their natural counterparts, chimeric antigen receptor-engineered cells are prone to suppression by inhibitory signals, such as PD-L1, expressed by tumors or suppressor cells in the tumor microenvironment. Consequently, they become impaired, resulting in immune cell exhaustion, tumor progression, and resistance to other therapies. In this study, we developed an anti-PD-L1-CAR NK cell with efficient activity and a notable PD-L1-specific response toward tumor cell lines. The degranulation assay demonstrated that CD107a frequencies between the PD-L1<sup>med</sup> and PD-L1<sup>high</sup> groups and between Herceptin-treated and non-treated groups were not statistically different. Further investigation into NK cell characterization, considering different markers such as CD57, KIR2D, and CD25, revealed that the majority of the population are activated expanding NK cells. At the same time, immune checkpoint inhibitors, including PD-1, PD-L1, and LAG-3, showed increased levels following activation and expansion. Regarding the efficient functional activity of PD-L1-CAR NK cells and the instinctive receptor balance-based response of NK cells, this observation could point to the inhibition of NK cell overactivation or even higher cytotoxicity and cytokine production rather than exhaustion, especially in the case of healthy NK cells. These findings can contribute to a better understanding of the potential and challenges of using primary NK cells for CAR-NK cell therapy.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"1115-1127"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic drives affecting Th17/Treg gene expression changes and differentiation: impact on immune-microenvironment regulation.","authors":"Carolina Brescia, Salvatore Audia, Alessia Pugliano, Federica Scaglione, Rodolfo Iuliano, Francesco Trapasso, Nicola Perrotti, Emanuela Chiarella, Rosario Amato","doi":"10.1111/apm.13378","DOIUrl":"10.1111/apm.13378","url":null,"abstract":"<p><p>The CD4<sup>+</sup> T-cell population plays a vital role in the adaptive immune system by coordinating the immune response against different pathogens. A significant transformation occurs in CD4<sup>+</sup> cells during an immune response, as they shift from a dormant state to an active state. This transformation leads to extensive proliferation, differentiation, and cytokine production, which contribute to regulating and coordinating the immune response. Th17 and Treg cells are among the most intriguing CD4<sup>+</sup> T-cell subpopulations in terms of genetics and metabolism. Gene expression modulation processes rely on and are linked to metabolic changes in cells. Lactylation is a new model that combines metabolism and gene modulation to drive Th17/Treg differentiation and functional processes. The focus of this review is on the metabolic pathways that impact lymphocyte gene modulation in a functionally relevant manner.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"1026-1045"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApmisPub Date : 2024-12-01Epub Date: 2024-06-14DOI: 10.1111/apm.13447
Sana Ahuja, Niti Sureka, Sufian Zaheer
{"title":"Unraveling the intricacies of cancer-associated fibroblasts: a comprehensive review on metabolic reprogramming and tumor microenvironment crosstalk.","authors":"Sana Ahuja, Niti Sureka, Sufian Zaheer","doi":"10.1111/apm.13447","DOIUrl":"10.1111/apm.13447","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are crucial component of tumor microenvironment (TME) which undergo significant phenotypic changes and metabolic reprogramming, profoundly impacting tumor growth. This review delves into CAF plasticity, diverse origins, and the molecular mechanisms driving their continuous activation. Emphasis is placed on the intricate bidirectional crosstalk between CAFs and tumor cells, promoting cancer cell survival, proliferation, invasion, and immune evasion. Metabolic reprogramming, a cancer hallmark, extends beyond cancer cells to CAFs, contributing to the complex metabolic interplay within the TME. The 'reverse Warburg effect' in CAFs mirrors the Warburg effect, involving the export of high-energy substrates to fuel cancer cells, supporting their rapid proliferation. Molecular regulations by key players like p53, Myc, and K-RAS orchestrate this metabolic adaptation. Understanding the metabolic symbiosis between CAFs and tumor cells opens avenues for targeted therapeutic strategies to disrupt this dynamic crosstalk. Unraveling CAF-mediated metabolic reprogramming provides valuable insights for developing novel anticancer therapies. This comprehensive review consolidates current knowledge, shedding light on CAFs' multifaceted roles in the TME and offering potential targets for future therapies.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"906-927"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApmisPub Date : 2024-12-01Epub Date: 2023-09-17DOI: 10.1111/apm.13344
Mads Lichtenberg, Klaus Kirketerp-Møller, Lasse A Kvich, Mads Holm Christensen, Blaine Fritz, Tim Holm Jakobsen, Thomas Bjarnsholt
{"title":"Single cells and bacterial biofilm populations in chronic wound infections.","authors":"Mads Lichtenberg, Klaus Kirketerp-Møller, Lasse A Kvich, Mads Holm Christensen, Blaine Fritz, Tim Holm Jakobsen, Thomas Bjarnsholt","doi":"10.1111/apm.13344","DOIUrl":"10.1111/apm.13344","url":null,"abstract":"<p><p>Chronic wounds and chronic ulcers are an increasing problem associated with high health care burden and patient burden. The arrested healing of chronic wounds has, in part, been attributed to the presence of biofilms. Substantial research has documented the presence of biofilms in chronic wounds, and many mechanisms of host-pathogen interactions have been uncovered to explain the arrested healing. However, the paradigm of whether biofilms are only observed in chronic infections was recently challenged when biofilms were also observed in acute infections. Here, we characterize the distribution of bacteria in lower leg wounds with particular emphasis on Pseudomonas aeruginosa and Staphylococcus aureus by confocal laser scanning microscopy combined with PNA-FISH staining and routine culture of bacteria. We show that 40% of wounds contained either P. aeruginosa or S. aureus biofilms and demonstrate the presence of scattered single cells in tissues stained with a universal bacterial PNA-FISH probe. Thus, we demonstrate that chronic wounds do not only harbor bacteria organized in biofilms, but also carry populations of scattered single cells and small cell clusters of only a few bacteria. Our findings may influence diagnostic tools being developed to only target biofilms, where single-cell subpopulations thus may be overlooked and possibly lead to false-negative results.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"1071-1077"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApmisPub Date : 2024-12-01Epub Date: 2024-11-12DOI: 10.1111/apm.13490
Maria Bech Damsgaard Nielsen, Andrea René Jørgensen, Maiken Stilling, Mads Kristian Duborg Mikkelsen, Nis Pedersen Jørgensen, Mats Bue
{"title":"Dynamic distribution of systemically administered antibiotics in orthopeadically relevant target tissues and settings.","authors":"Maria Bech Damsgaard Nielsen, Andrea René Jørgensen, Maiken Stilling, Mads Kristian Duborg Mikkelsen, Nis Pedersen Jørgensen, Mats Bue","doi":"10.1111/apm.13490","DOIUrl":"10.1111/apm.13490","url":null,"abstract":"<p><p>This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English-published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady-state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":"992-1025"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phylogeogenomic analysis of the earliest reported sequences of SARS-CoV-2 from 161 countries.","authors":"Rezwanuzzaman Laskar, Mehboob Hoque, Safdar Ali","doi":"10.1111/apm.13499","DOIUrl":"https://doi.org/10.1111/apm.13499","url":null,"abstract":"<p><p>The SARS-CoV-2 is the causative agent of COVID-19 whose evolutionary path with geographical context forms the focus of present study. The first reported sequence from each of the 161 countries was downloaded from the GISAID database. Multiple sequence alignment was performed using MAFFT v.7, and a TCS-based network was constructed using PopART v.1.7. A total of 27 proteins were analyzed including structural and non-structural proteins. NSP3 and NSP12, responsible for viral replication and RNA synthesis, respectively, had the highest mutation incidence and frequency among non-structural proteins. The spike (S) protein, critical for viral attachment and entry, had the highest prevalence and frequency of mutations. ORF3a had the highest mutation incidence and frequency among accessory proteins. The phylogeogenomic network identified six haplogroups containing 35 sequences, while the remaining sequences belonged to different haplotypes. The virus's genetic distinctiveness was higher in European genomes, with four haplogroups dominated by Europe-linked sequences. The triangular-shaped pattern observed in the virus's evolutionary path suggests that it spread to different continents from Asia. Multiple transmission pathways connecting different countries affirm the virus's ability to emerge in multiple countries by early 2020. The possibility of new species emergence through \"saltation\" due to the pandemic is also discussed.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}