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Ahuja, Sana; Sureka, Niti; Zaheer, Sufian
doi: 10.1111/apm.13447pmid: 38873945
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.
doi: 10.1111/apm.13356pmid: 37941500
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.
Kong, Jing; Yang, Juan; He, Cong; Zhou, Bingduo; Fang, Shengquan; Salinas, Manisha; Mohabbat, Arya B.; Bauer, Brent A.; Wang, Xiaosu
doi: 10.1111/apm.13473pmid: 39370693
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.
doi: 10.1111/apm.13412pmid: 38571459
Oral candidiasis (OC), a prevalent opportunistic infection of the oral mucosa, presents a considerable health challenge, particularly in individuals with compromised immune responses, advanced age, and local predisposing conditions. A considerable part of the population carries Candida in the oral cavity, but only few develop OC. Therefore, the pathogenesis of OC may depend on factors other than the attributes of the fungus, such as host factors and other predisposing factors. Mucosal trauma and inflammation compromise epithelial integrity, fostering a conducive environment for fungal invasion. Molecular insights into the immunocompromised state reveal dysregulation in innate and adaptive immunity, creating a permissive environment for Candida proliferation. Detailed examination of Candida species (spp.) and their virulence factors uncovers a nuanced understanding beyond traditional C. albicans focus, which embrace diverse Candida spp. and their strategies, influencing adhesion, invasion, immune evasion, and biofilm formation. Understanding the pathophysiological microenvironments in OC is crucial for the development of targeted therapeutic interventions. This review aims to unravel the diverse pathophysiological microenvironments influencing OC development focusing on microbial, host, and predisposing factors, and considers Candida resistance to antifungal therapy. The comprehensive approach offers a refined perspective on OC, seeking briefly to identify potential therapeutic targets for future effective management.
Bay, Lene; Jemec, Gregor Borut; Ring, Hans Christian
doi: 10.1111/apm.13464pmid: 39270740
Several microbiome studies have recently demonstrated microbial dysbiosis in various chronic inflammatory skin diseases, and it is considered an important role in the pathogenesis. Although the role of skin dysbiosis in inflammatory skin diseases is debatable, the local microenvironment is considered essential concerning compositional changes and functional alterations of the skin microbiota. Indeed, various local nutrients (e.g., lipids), pH values, water, oxygen, and antimicrobial peptides may affect the level of skin dysbiosis in these skin diseases. In particular, in atopic dermatitis and hidradenitis suppurativa, significant changes in skin dysbiosis have been associated with local aberrant host immune changes. In this review, the potential pathogenic crosstalk between the host and the microbiota is reviewed in relation to the physical, chemical, and biological microenvironments of various chronic inflammatory skin diseases.
Høiby, Niels; Moser, Claus; Ciofu, Oana
doi: 10.1111/apm.13405pmid: 38565324
Antibiotic susceptibility testing (AST) by agar diffusion has been repeatedly standardized and, in most cases, gives results which predict clinical success when antibiotic treatment is based on such results. The formation of the inhibition zone is due to a transition from planktonic to biofilm mode of growth. The kinetics of the interaction of antibiotics with bacteria is similar during AST by agar diffusion and during administration of antibiotics to the patients. However, the Mueller‐Hinton agar (MHA) recommended for AST agar diffusion test is fundamentally different from the composition of the interstitial fluid in the human body where the infections take place and human cells do not thrive in MH media. Use of RPMI 1640 medium designed for growth of eucaryotic cells for AST of Pseudomonas aeruginosa against azithromycin results in lower minimal inhibitory concentration, compared to results obtained by MHA. The reason is that the RPMI 1640 medium increases uptake and reduces efflux of azithromycin compared to MHA. During treatment of cystic fibrosis patients with azithromycin, mutational resistance occur which is not detected by AST with MHA. Whether this is the case with other antibiotics and bacteria is not known but it is of clinical importance to be studied.
Nielsen, Maria Bech Damsgaard; Jørgensen, Andrea René; Stilling, Maiken; Mikkelsen, Mads Kristian Duborg; Jørgensen, Nis Pedersen; Bue, Mats
doi: 10.1111/apm.13490pmid: 39530161
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.
Brescia, Carolina; Audia, Salvatore; Pugliano, Alessia; Scaglione, Federica; Iuliano, Rodolfo; Trapasso, Francesco; Perrotti, Nicola; Chiarella, Emanuela; Amato, Rosario
doi: 10.1111/apm.13378pmid: 38239016
The CD4+ 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+ 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+ 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.
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