Rui Ji, Hong Yang, Jiamei Chen, Anna Zhao, Xia Chen, Yanli Niu
{"title":"The role of hsa_circ_0042260/miR-4782-3p/LAPTM4A axis in gestational diabetes mellitus","authors":"Rui Ji, Hong Yang, Jiamei Chen, Anna Zhao, Xia Chen, Yanli Niu","doi":"10.1111/apm.13407","DOIUrl":"10.1111/apm.13407","url":null,"abstract":"<p>Gestational diabetes mellitus (GDM) is a common metabolic condition during pregnancy, posing risks to both mother and fetus. CircRNAs have emerged as important players in various diseases, including GDM. We aimed to investigate the role of newly discovered circRNA, hsa_circ_0042260, in GDM pathogenesis. Using GSE194119 dataset, hsa_circ_0042260 was identified and its expression in plasma, placenta, and HG-stimulated HK-2 cells was examined. Silencing hsa_circ_0042260 in HK-2 cells assessed its impact on cell viability, apoptosis, and inflammation. Bioinformatics analysis revealed downstream targets of hsa_circ_0042260, namely miR-4782-3p and LAPTM4A. The interaction between hsa_circ_0042260, miR-4782-3p, and LAPTM4A was validated through various assays. hsa_circ_0042260 was upregulated in plasma from GDM patients and HG-stimulated HK-2 cells. Silencing hsa_circ_0042260 improved cell viability, suppressed apoptosis and inflammation. Hsa_circ_0042260 interacted with miR-4782-3p, which exhibited low expression in GDM patient plasma and HG-stimulated cells. MiR-4782-3p targeted LAPTM4A, confirmed by additional assays. LAPTM4A expression increased in GDM patient plasma and HG-induced HK-2 cells following hsa_circ_0042260 knockdown or miR-4782-3p overexpression. In rescue assays, inhibition of miR-4782-3p or overexpression of LAPTM4A counteracted the effects of hsa_circ_0042260 downregulation on cell viability, apoptosis, and inflammation. In conclusion, the hsa_circ_0042260/miR-4782-3p/LAPTM4A axis plays a role in regulating GDM progression in HG-stimulated HK-2 cells.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"465-476"},"PeriodicalIF":2.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575745","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":"Pathophysiological microenvironments in oral candidiasis","authors":"Mette Rose Jørgensen","doi":"10.1111/apm.13412","DOIUrl":"10.1111/apm.13412","url":null,"abstract":"<p>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 <i>Candida</i> 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 <i>Candida</i> proliferation. Detailed examination of <i>Candida</i> species (spp.) and their virulence factors uncovers a nuanced understanding beyond traditional <i>C. albicans</i> focus, which embrace diverse <i>Candida</i> 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 <i>Candida</i> resistance to antifungal therapy. The comprehensive approach offers a refined perspective on OC, seeking briefly to identify potential therapeutic targets for future effective management.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"956-973"},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575732","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":"The microenvironment in antibiotic susceptibility testing","authors":"Niels Høiby, Claus Moser, Oana Ciofu","doi":"10.1111/apm.13405","DOIUrl":"10.1111/apm.13405","url":null,"abstract":"<p>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 <i>Pseudomonas aeruginosa</i> 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.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"985-991"},"PeriodicalIF":2.2,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575735","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}
Johanna T. Teräsjärvi, Laura Toivonen, Jussi Mertsola, Ville Peltola, Qiushui He
{"title":"ST2 and IL-33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children","authors":"Johanna T. Teräsjärvi, Laura Toivonen, Jussi Mertsola, Ville Peltola, Qiushui He","doi":"10.1111/apm.13411","DOIUrl":"10.1111/apm.13411","url":null,"abstract":"<p>The ST2/IL-33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of <i>ST2</i> and <i>IL-33</i> polymorphisms with serum soluble (s) ST2 and IL-33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single-nucleotide polymorphisms (SNPs) in <i>ST2</i> and <i>IL-33</i> were determined, and associations of the SNP variants with serum levels of sST2 and IL-33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with <i>ST2</i> rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with <i>ST2</i> rs13408661. No differences were observed between subjects with studied <i>IL-33</i> SNPs. Children who carried genetic variants of <i>ST2</i> rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of <i>IL-33</i> rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 7","pages":"515-525"},"PeriodicalIF":2.8,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575733","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":"Exploring the immune-modulating properties of boswellic acid in experimental autoimmune encephalomyelitis","authors":"Alireza Shadab, Mohammad Abbasi-Kolli, Esmaeil Yazdanpanah, Seyed-Alireza Esmaeili, Rasoul Baharlou, Bahman Yousefi, Dariush Haghmorad","doi":"10.1111/apm.13406","DOIUrl":"10.1111/apm.13406","url":null,"abstract":"<p>Multiple sclerosis (MS) is a condition where the central nervous system loses its myelin coating due to autoimmune inflammation. The experimental autoimmune encephalomyelitis (EAE) simulates some aspects of human MS. Boswellic acids are natural compounds derived from frankincense extract, known for their anti-inflammatory properties. The purpose of this research was to investigate therapeutic potential of boswellic acids. Mice were divided into three groups: low-dose (LD), high-dose (HD), and control groups (CTRL). Following EAE induction, the mice received daily doses of boswellic acid for 25 days. Brain tissue damage, clinical symptoms, and levels of TGF-β, IFN-γ, and IL-17 cytokines in cell cultured supernatant of lymphocytes were assessed. Gene expression of transcription factors in brain was measured using real-time PCR. The levels of brain demyelination were significantly lower in the treatment groups compared to the CTRL group. Boswellic acid reduced the severity and duration of EAE symptoms. Furthermore, boswellic acid decreased the amounts of IFN-γ and IL-17, also the expression of T-bet and ROR-γt in brain. On the contrary, it increased the levels of TGF-β and the expression FoxP3 and GATA3. Our findings suggest that boswellic acids possess therapeutic potential for EAE by modulating the immune response and reducing inflammation.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"452-464"},"PeriodicalIF":2.8,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334490","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":"Pharmacokinetic and pharmacodynamic evaluation of nitrofurantoin against Escherichia coli in a murine urinary tract infection model","authors":"Marit Gaastra Maaland, Lotte Jakobsen, Luca Guardabassi, Niels Frimodt-Møller","doi":"10.1111/apm.13409","DOIUrl":"10.1111/apm.13409","url":null,"abstract":"<p>The antimicrobial agent nitrofurantoin is becoming increasingly important for treatment of urinary tract infections (UTIs) due to widespread occurrence of multidrug-resistant <i>Escherichia coli</i>. Despite many years of use, little data on nitrofurantoin pharmacokinetics (PK) or -dynamics (PD) exist. The objective of this study was to (i) evaluate the pharmacokinetics of nitrofurantoin in a mouse model and (ii) use that data to design an in vivo dose fractionation study in an experimental model of UTI with <i>E. coli</i> for determination of the most predictive PK/PD index. Nitrofurantoin concentrations in urine were approximately 100-fold larger than concentrations in plasma after oral administration of 5, 10, and 20 mg/kg nitrofurantoin. The area under the curve over the minimum inhibitory concentration (AUC/MIC) was weakly correlated to bacterial reduction in urine (r<sup>2</sup> = 0.24), while no such correlation was found for the time that nitrofurantoin stayed above the MIC (T > MIC). Increasing size of single-dose treatment was significantly correlated to eradication of bacteria in the urine, while this was not apparent when the same doses were divided in 2 or 3 doses 8 or 12 h apart. In conclusion, the results indicate that nitrofurantoin activity against <i>E. coli</i> in urine is driven by AUC/MIC.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 7","pages":"492-498"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334491","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":"Rapid identification of SARS-CoV-2 variants using stable high-frequency mutation sites","authors":"Yu Fu, Xiaobai He, Quan Fang, Fei Kong, Yan Zhang, Ting Fu, Liang Chen, YanXin Liu, Zhen Wang, Jianxin Lyu, Linjie Chen","doi":"10.1111/apm.13388","DOIUrl":"10.1111/apm.13388","url":null,"abstract":"<p>Respiratory infectious viruses, including SARS-CoV-2, undergo rapid genetic evolution, resulting in diverse subtypes with complex mutations. Detecting and differentiating these subtypes pose significant challenges in respiratory virus surveillance. To address these challenges, we integrated ARMS-PCR with molecular beacon probes, allowing selective amplification and discrimination of subtypes based on adjacent mutation sites. The method exhibited high specificity and sensitivity, detecting as low as 10<sup>4</sup> copies/mL via direct fluorescence analysis and ~10<sup>6</sup> copies/mL using real-time PCR. Our robust detection approach offers a reliable and efficient solution for monitoring evolving respiratory infections, aiding early diagnosis and control measures. Further research could extend its application to other respiratory viruses and optimize its implementation in clinical settings.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 5","pages":"348-357"},"PeriodicalIF":2.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130591","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}
Elina Saarela, Marjo Renko, Matti Uhari, Tytti Pokka, Heikki Kauma, Terhi S. Ruuska
{"title":"Multiplex PCR for respiratory bacteria in acute care","authors":"Elina Saarela, Marjo Renko, Matti Uhari, Tytti Pokka, Heikki Kauma, Terhi S. Ruuska","doi":"10.1111/apm.13403","DOIUrl":"10.1111/apm.13403","url":null,"abstract":"<p>The purpose of the study was to evaluate the clinical utility of multiplex PCR for detecting bacterial respiratory pathogens in nasopharyngeal samples. Acutely ill adults in the emergency department with respiratory infection symptoms, fever, chest pain or poor general condition were enrolled for this cohort study. Samples were stored at –70 °C until being analysed with multiplex PCR for seven respiratory bacteria. Of the 912 patients enrolled, those with positive bacterial samples (n = 130, 14%) were significantly younger than those with a negative finding (55.5 years vs 62.2 years, p < 0.001), and their mean C-reactive protein (CRP) concentration was higher (110 mg/L vs 59 mg/L, p < 0.0001). Patients with a positive respiratory bacterial finding had a higher probability of pneumonia (35% vs 13%, p < 0.001) and a higher likelihood of receiving a prescription for antibiotics than those with a negative finding (79% vs 59%, p < 0.0001). Positive detection of <i>Streptococcus pneumoniae</i> was associated with a 4.5-fold risk of pneumonia in a multivariate model and detection of an atypical respiratory pathogen with a 9-fold risk. Bacterial PCR performed on nasopharyngeal samples appeared to offer a valuable addition to the diagnostics of infections in adults in acute care.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"444-451"},"PeriodicalIF":2.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118573","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}
Zi-feng Lu, Chou-Yi Hsu, Nada Khairi Younis, Mohammed Ahmed Mustafa, Elena A. Matveeva, Yassien Hussain Owaied Al-Juboory, Mohaned Adil, Zainab H. Athab, Mustafa Nasrat Abdulraheem
{"title":"Exploring the significance of microbiota metabolites in rheumatoid arthritis: uncovering their contribution from disease development to biomarker potential","authors":"Zi-feng Lu, Chou-Yi Hsu, Nada Khairi Younis, Mohammed Ahmed Mustafa, Elena A. Matveeva, Yassien Hussain Owaied Al-Juboory, Mohaned Adil, Zainab H. Athab, Mustafa Nasrat Abdulraheem","doi":"10.1111/apm.13401","DOIUrl":"10.1111/apm.13401","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"382-415"},"PeriodicalIF":2.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100879","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}