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Bahareh Vakili,1 Abolfazl Fateh,2 Hamid Asadzadeh Aghdaei,3 Fattah Sotoodehnejadnematalahi,1 Seyed Davar Siadat2 1Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran; 2Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran; 3Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Seyed Davar Siadat Tel +98 2164112282Fax +98 2166465132Email siadat2019@gmail.comPurpose: The incidence of Clostridioides difficile infection (CDI) has been reported as 10-fold higher among the elderly population than in young adults. The aim of this study was to compare the targeted bacteria population in the fecal microbiota in two groups of hospitalized elderly, categorized according to CDI and non-CDI.Patient and Methods: In this case–control study, 84 fecal samples of the 28 patients with CDI and 56 non-CDI patients (> 65 years) were studied. C. difficile isolates were characterized by anaerobic culture and multiplex PCR. Quantitative PCR was used to analyze the bacterial elements.Results: CDI group differed significantly for a prolonged hospital stay, previous surgery, residence in nursing home and exposure to a range of antibiotics including quinolone, clindamycin and cephalosporin. CDI group had significantly fewer members of Bacteroides spp., Clostridium cluster IV, Bifidobacterium spp., Faecalibacterium prausnitzii, and Prevotella spp. in their fecal microbiota than the control group (P < 0.05). The abundances of Akkermansia muciniphila, Lactobacillus spp., Escherichia coli and Klebsiella spp. were higher in group CDI compared with the control group (P < 0.05).Conclusion: CDI status is associated with the abundance of some bacterial populations. In this study, an increase in Akkermansia muciniphila, Lactobacillus spp., and Enterobacteriaceae genus was highlighted in CDI patients. A reduction in butyrate-producing bacteria was found in CDI patients. The differences in the composition of fecal microbiota can help to understand how antimicrobial agents impact on gut homeostasis and lead to loss of colonization resistance to C. difficile.Keywords: Clostridioides difficile, risk factors, elderly, fecal microbiota

Mohsen Tabasi,1,2 Seyed Alireza Javadinia,3 Seyed Davar Siadat,4 Sana Eybpoosh,5 Mohammad Reza Yazdannasab,4 Milad Kheirvari,4 Fezzeh Elyasinia,6 Saeed Bayanolhagh,7 Amin Radmanesh,2 Ahmadreza Soroush8 1Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran; 2Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran; 3Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran; 4Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran; 5Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran; 6Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran; 7Iranian Research Center of HIV/AIDS, Tehran University of Medical Sciences, Tehran, Iran; 8Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Ahmadreza SoroushObesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, IranEmail soroush1344@gmail.comAbstract: Laparoscopic sleeve gastrectomy (LSG) is an effective treatment option in patients with morbid obesity, with rare long-term sideeffects. In this report, we present a 42-year-old woman who reported positional vertigo and unilateral gradual hearing loss plus continuous tinnitus after LSG. The patient had no signs or symptoms of mental health disorders and the results of the haematological and serum biochemical tests were normal. However, audiometric test revealed mild sensorineural hearing loss with magnitude in high-frequency tones. Also, acoustic reflex threshold showed neural pathway damage, particularly at high frequencies, with no reflex. Pure tone audiometry showed signs of nerve damage in the inner ear. One possible justification for these complications might be eustachian tube dysfunction due to muscle relaxation. Muscle relaxation itself may occur as a result of adipose tissue loss around the ear muscles. Further evidence, however, would be required to better determine whether these complications are attributable to LSG, and to illuminate exact underlying reasons for such complications.Keywords: hearing loss, positional vertigo, sleeve gastrectomy, bariatric surgery, obesity

Zahra Mortazavi,1 Ahmadreza Bahrmand,2 Fatemeh Sakhaee,2 Reza Hosseini Doust,1 Farzam Vaziri,2,3 Seyed Davar Siadat,2,3 Abolfazl Fateh2,31Department of Microbiology, Faculty of Advance Science, Tehran Medical Science, Islamic Azad University, Tehran, Iran; 2Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; 3Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, IranPurpose: Nontuberculous mycobacteria (NTM) infection is an increasing problem worldwide whose clinical significance is still largely unknown. The aim of this study was to investigate the epidemiology of NTM infection from respiratory samples and to determine their clinical significance.Patients and methods: This cross-sectional study was performed on 7,825 clinical samples from December 2015 to December 2017. Detection was conducted using phenotypic and genotypic (hsp65 PCR-RFLP, rpoB, and 16S rRNA genes sequencing) methods. All clinical information including symptoms and radiological findings was extracted from patients’ records.Results: A total of 478 were confirmed to have respiratory samples which were culture positive for mycobacteria, with the prevalence of NTM infection obtained as 53 (11.1%). Overall, Mycobacterium (M.) fortuitum was the most frequent NTM isolate, followed by M. simiae, M. kansasii, M. gordonae, and M. conceptionense. There was a relationship between NTM isolates and gender (P=0.039), symptoms (P=0.048), and radiographic findings (P=0.013). Bronchiectasis, infiltration, and cavitary lesion were the most frequent radiological findings in M. fortuitum, M. simiae, and M. kansasii, respectively, with cough being the most frequent symptom.Conclusion: We reported five different NTM isolates in respiratory samples with a high frequency of M. fortuitum. NTM infections may play an important role in causing pulmonary disease and in tuberculosis management in endemic settings. Nevertheless, more studies are required to further examine the clinical significance of NTM isolates.Keywords: nontuberculous mycobacteria, respiratory samples, clinical significance, Mycobacterium fortuitum

Mehdi Hajmohammadi,1 Seyed Davar Siadat,2 Masoud Ghorbani,3,4,* Mehdi Shafiee Ardestani,5,* Shahram Teimourian,6 Vahid Asgari,3 Reza Ahangari Cohan,3 Mostafa Hajmohammadi,5 Akram Hajmohammadi,7 Ramezan Behzadi,8 Saied Rajab Nezhad,9 Nabiollah Namvar Asl10 1Department of Research and Biotechnology, 2Department of Microbiology, 3Department of Virology, Pasteur Institute of Iran, Tehran Iran; 4Department of Virology, University of Ottawa, Ottawa, ON, Canada; 5Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Medical Genetics, Iran University of Medical Sciences, Tehran, 7Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 8Laboratory Animal Management of North Research Center, Pasteur Institute of Iran, 9Department of Research and Development, Alhavi Pharmaceutical, Tehran, 10Pasteur Institute of Iran, Department of Animal Sciences, Karaj, Iran *These authors contributed equally to this work Abstract: In recent years, many experiments have been conducted for the production and evaluation of anticancer glycoconjugated vaccines in developed countries and many achievements have been accomplished with Globo H derivatives. In the current experiment, a new chemically designed triplicate version of (Globo H)3–diethylenetriamine pentaacetic acid (DTPA)–KLH antigen was synthesized and characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a member of a family of antigenic carbohydrates that are highly expressed in various types of cancers conjugated with DTPA and KLH protein, induced a high level of antibody titer along with an elevated level of IL-4 in mice. Treatment of tumors with the collected sera from immunized mice decreased the tumor size in nude mice as well. None of the immunized mice illustrated any sign of tumor growth after injection of MCF-7 cells compared to the control animals. These findings, based on the newly presented structure of the Globo H antigen, lend exciting and promising evidence for clinical advancement in the development of a therapeutic vaccine in the future. Keywords: (Globo H)3-DTPA-KLH, glycoconjugate vaccines, breast cancer

Shiva Irani1, Seyed Mohammad Atyabi2, Houri Mivehchi3, Seyed Davar Siadat2, Mohammad Reza Aghasadeghi2, Ali Farhangi21Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; 2Department of Pilot Biotechnology, Pasteur Institute of Iran, Tehran, Iran; 3Department of Novel Drug Delivery System, Iran Polymer and Petrochemical Institute, Tehran, IranAbstract: The p53 tumor-suppressor protein is a cellular phosphoprotein and a negative regulator of cell growth. Most p53 mutations occur in exons 5–8 within the DNA-binding domain. Therefore, p53 can potentially be targeted with novel drugs designed to bind to a mutation and restore its stability or wild-type conformation. For the current study, Hartree–Fock calculations were used to investigate the solvent-induced effects of five different solvent media (acetone, ethanol, methanol, dimethyl sulfoxide, and water) on the thermochemical parameters and relative energies, and on the multinuclear nuclear magnetic resonance shielding tensors of oxygen, nitrogen, and phosphorus nuclei, of GAT. To understand how the solvent affects the mutation region (the “hot spot”) of p53, the relative energies of GAT in selected solvent media were determined. Some biological evidence suggested the structural stabilities of hot spots of GAT have the optimum temperature and solvent type for mutation. All the authors’ findings are in accordance with common biological phenomena. Another important objective of this study was to compare the hydration Gibbs free energies of CUA and GAT in water using two different approaches where the solvent was treated as a continuum of the constant at different levels of Hartree–Fock theory. The Gibbs hydration energy values obtained in water with the polarized continuum model directly applied on the isolated CUA and GAT sequences were compared with those determined from the hydrated models with four, six, and eight water molecule clusters around the hot spots uracil and adenine. The clustered structures of water molecules around the hot spots of GAT (in DNA level) and CUA (in transcriptional level) were found to be energetically favored. The results of this study provide a reliable insight into the nature of mutation processes, which is of utmost importance for the study of biochemical structures, and provide a basis for drug design.Keywords: polarized continuum model (PCM), nuclear magnetic resonance (NMR), Hartree–Fock theory

Background and Objective: Human immunodeficiency virus (HIV) belongs to the retroviridae family and is the agent of acquired immunodeficiency syndrome (AIDS). Treatment of HIV for the global health has made a special importance for the new antiviral drug discoveries in addition to HIV vaccine developments. Materials and Methods: In this experimental study single cycle replicable (SCR) HIV-1 virions with the capability of one cycle of replication were produced by the co-transfection of three plasmids of pmzNL4-3, psPAX2 and pMD2.G to the HEK cells and their replication capacity of the first generation SCR visions in HEK 293T, MT-2, and mouse spleen cells was examined by p24-capture ELISA, syncytium formation assay. The infectivity of the SCR-produced virions was also analysed on MT-2 cells. Results: Experiments showed the efficient production of SCR virions. Moreover, results indicated the replication potency of SCR virions on the investigated cells and the inactivity of the produced SCR HIV virions. Complete HIV antigens are expressed in their native forms by SCR virions, but this second viral particles lack the replication capacity. Conclusion: SCR HIV virions produced in this study are capable of one cycle of replication and will be inactivated thereafter.These features make SCR virions as a good candidate for HIV vaccine studies. Moreover, considering the one cycle replication, SCR virions do not need the severe biosafety concerns involved in retrovirus studies.

Background: The implication of gut microbiota in the gut-kidney axis affects the pathophysiology of chronic kidney disease (CKD). Gut microbiota composition changes during CKD. We aimed to determine the relative frequency of important gut microbiota members in end-stage renal disease (ERSD) patients before and after renal transplantation compared to healthy subjects., Methods: Fifteen kidney transplant patients and 10 healthy subjects were recruited in this case-control prospective study. Fecal samples were taken sequentially from all patients before kidney transplantation, 1 week, and 1 month after it. The relative frequency of Lactobacillus spp., Bifidobacterium spp., Akkermansia muciniphila, Bacteroides fragilis, Escherichia coli , and Faecalibacterium pruasnitzii were determined through quantitative PCR. The obtained data was statistically analyzed by Stata software (Stata Corporation, USA)., Results: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients ( p  < 0.001) except for Lactobacillus where the mean levels were almost identical in the two groups ( p  = 0.67). Moreover, 20% (3) of patients developed a urinary tract infection. Besides, 2 (13.33%) patients were diagnosed with delayed graft function. There were no statistically significant differences regarding changing trends in bacteria log number of Akkermansia muciniphila ( p  = 0.12), Bacteroid fragilis ( p  = 0.75), Bifidobacterium ( p  = 0.99), Escherichia coli ( p  = 0.5), Faecalibacterium ( p  = 0.98), and Lactobacilli ( p  = 0.93) between patients with and without delayed graft function (DGF)., Conclusion: Gut microbiota composition in patients with ESRD was significantly different from those without it. However, the microbiota profile did not significantly differ in patients with and without DGF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The intratumoral microbiome (ITM) is in the spotlight due to its possible contribution to the initiation, progression, and invasion of a wide range of cancers. Its precise contribution to cancer tumorigenesis is still elusive, though. Thyroid cancer(TC), the ninth leading cause of cancer globally and the most prevalent endocrine malignancy with a rapidly rising incidence among all cancers, has attracted much attention nowadays. Still, the association between the tumor's microbiome and TC progression and development is an evolving area of investigation with significant consequences for disease understanding and intervention. Therefore, this review offers an appropriate perspective on this emerging concept in TC based on prior studies on the ITM among the most common tumors worldwide, concentrating on TC. Moreover, information on the origin of the ITM and practical methods can pave the way for researchers to opt for the most appropriate method for further investigations on the ITM more accurately., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Hessam Yaghmaei et al.)

Pulmonary fibrosis (PF) is a progressive and debilitating respiratory condition characterized by excessive deposition of extracellular matrix proteins and scarring within the lung parenchyma. Despite extensive research, the pathogenesis of PF remains incompletely understood, and effective therapeutic options are limited. Emerging evidence suggests a potential link between gut microbiota dysbiosis and the development of PF, highlighting the gut-lung axis as a promising therapeutic target. Akkermansia muciniphila (A. muciniphila), a mucin-degrading bacterium residing in the gut mucosal layer, has garnered considerable interest due to its immunomodulatory and anti-inflammatory properties. This study investigates the therapeutic potential of live and pasteurized A. muciniphila, as well as its extracellular vesicles (EVs), in mitigating inflammation and fibrosis in a murine model of carbon tetrachloride (CCl4)-induced PF exacerbated by a high-fat diet (HFD). Male C57BL/6 mice were divided into groups receiving either a normal diet or an HFD, with or without CCl4 administration. The mice were then treated with live or pasteurized A. muciniphila, or its EVs. Lung tissue was analyzed for the expression of inflammatory markers and fibrosis markers using real-time PCR and ELISA. Administration of live and pasteurized A. muciniphila, as well as its EVs, significantly downregulated the expression of inflammatory and fibrosis markers in the lung tissue of CCl4-induced PF mice. Furthermore, these treatments ameliorated the increased production of IL-6 and reduced IL-10 levels observed in the HFD and CCl4-treated groups. These findings suggest that A. muciniphila and its derivatives exert protective effects against pulmonary inflammation and fibrosis, potentially through modulation of the gut-lung axis. The study highlights the therapeutic potential of A. muciniphila and its derivatives as novel interventions for the management of PF, warranting further preclinical and clinical investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study explores methods to isolate high-pure monocytes and optimize the best growth factor concentration to generate monocytes-derived dendritic cells (mo-DCs), subset DC1, which is crucial in immune responses. Three protocols for monocyte isolation from peripheral blood mononuclear cells (PBMCs) were evaluated: three-hour incubation on FBS-coated flasks; an overnight incubation on FBS-coated flasks; and Magnetic Activated Cell Sorting (MACS). Additionally, five different concentrations of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and human recombinant interleukin-4 (hrIL-4) were compared. We used Flow cytometry to assess the isolation, purification, and generation of pure monocytes characterized as CD14 + , and expression of mo-DC classical markers (HLA-DR, CD80, CD83, and CD86). The obtained results show that monocytes isolated with the second method (overnight incubation) had the highest purity (P < 0.0001) but the lowest yield (P > 0.05), balancing purity and cost-effectiveness. A combination of hrGM-CSF and hrIL-4 at 400 U/mL produced the most favorable outcomes, leading to the highest rate of mo-DC generation (P < 0.05). Notably, this concentration resulted in increasing expression of HLA-DR, CD80, and CD86 surface markers in the generated DCs (P < 0.0001), with no changes in CD83 expression levels. In conclusion, this study offers valuable insights into selecting the optimal approach for monocyte isolation and mo-DC generation in various research contexts, providing a foundation for more effective immunological studies., (© 2024. The Author(s).)

Mental health is affected by tryptophane (TRP) metabolism regulation. Diet-influenced gut microbiome regulates TRP metabolism. Thus, the present study aimed to explore the relationship between type of dietary protein intake, gut microbiota, TRP metabolites homeostasis, and mental well-being in healthy women. 91 healthy females aged 18-50 were recruited based on the study protocol. Validate and reliable questionnaires assessed dietary intake and mental health. Biochemical tests and gut microbiota composition were analyzed following the manufacturer's instructions for each enzyme-linked immune sorbent assay (ELISA) kit and Real-time quantitative polymerase chain reaction (qPCR) methods respectively. Regression methods were used to estimate the considered associations. The results show that in the fully adjusted model, plant protein consumption was partially inversely associated with depression risk (OR = 0.27; 95% CI: 0.06, 1.09; P = 0.06). Higher dietary animal protein intake was marginally associated with psychological distress (OR = 2.59; 95% CI: 0.91, 7.34; P = 0.07). KYN to serotonin ratio was inversely associated with animal protein consumption (ß = 1.10; 95% CI: -0.13, 2.33; P = 0.07). Firmicutes/Bacteriodetes ratio (β = -1.27 × 103, SE = 5.99 × 102, P = 0.03) was lower in the top tertile of plant protein. A partially negative correlation was found between dietary animal protein and Prevotella abundance (β = -9.20 × 1018, SE = 5.04 × 1018, P = 0.06). Overall, significant inverse associations were found between a diet high in plant protein with mental disorders, KYN levels, and Firmicutes to Bacteroidetes ratio while adhering to higher animal protein could predispose women to psychological stress., (© 2024. The Author(s).)

Purpose: One highlighted pathogenesis mechanism of diseases is the negative impact of pro-inflammatory diets (PD) on the gut microbiome. This systematic review aimed to study the link between dietary inflammatory index (DII), as an indicator of PD, and gut microbiome., Methods: A systematic search was done in PubMed and Scopus, adhering to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The assessment of the included studies' quality was performed using the critical appraisal checklist from the Joanna Briggs Institute., Results: Ten articles were included eight cross-sectional, one case-control, and, one cohort study. Seven and three included articles reported a weak and moderate relationship between gut microbiome and DII scores, respectively. DII scores were linked to variety in microbiome composition and diversity/richness. More importantly, anti-inflammatory diets as measured by lower DII scores were linked to a more desirable gut microbiome profile. Prevotella stercorea, Veillonella rogosae, Morganella morganii, Ruminococcus torques, Eubacterium nodatum, Alistipes intestine, Clostridium leptum, Morganellaceae family, Enterobacteriaceae family, and, Bacteroides thetaiotaomicron were related to higher DII scores. While, Butyrate-producing bacteria such as Ruminococcaceae and Lachnospiraceae families, Faecalibacterium prausnitzii, and Akkermansia muciniphila were related to lower DII scores., Conclusion: An anti-inflammatory diet, as measured by a lower DII score, might be linked to variations in the composition and variety of the microbiome. Therefore, the DII score could be useful in microbiota research, however, this possibility needs to be investigated more precisely in future studies., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Cutaneous infections caused by Mycobacterium chelonae can present with a variety of clinical symptoms, depending on the patient's immune status. Here, we report a case involving a 46-year-old woman with multiple sclerosis who developed a cutaneous infection caused by M. chelonae. The initial presentation included skin discoloration on her right wrist, which progressed to a granuloma. Following surgical intervention, the infection led to tissue atrophy and the formation of a deep cavity at the site. Upon identification of the causative pathogen, a treatment regimen consisting of clarithromycin and moxifloxacin was initiated and continued for seven months. The patient showed signs of recovery, with the swelling and deep cavity resolving; however, some redness at the site persists. The patient remains under treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: To delineate alterations in DNA methylation at high resolution within the genomic profile of monocyte-derived-dendritic cells (mo-DCs) in connection with Mycobacterium tuberculosis (MTB) infection, with particular emphasis on pro/ anti-inflammatory genes., Methods: In the context of this investigation, mo-DCs were infected by various active strains of MTB (Rifampicin-resistant [RIFR], H37Rv, multidrug-resistant [MDR], and extensively drug-resistant [XDR]). Subsequently, the pro/anti-inflammatory hub gene expression levels within the IL-6, IL-12, IFN-γ, IL-1β, TNF-α, and IL-10 pathways were evaluated employing real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, the effects of MTB infection on mo-DC protein expression were examined through western blot analysis. The methylation status (%) of TNF-α and IL-10 was considered through Methylation Sensitive-High Resolution Melting (MS-HRM)., Results: The results revealed an up-regulation of all pro-inflammatory genes among all groups, with TNF-α exhibiting the highest expression level. Conversely, the anti-inflammatory gene (IL-10) showed a down-regulated expression level. Furthermore, the DNA methylation status (%) of TNF-α decreased significantly among all the groups (P < 0.001), although there were no notable distinctions in the DNA methylation status (%) of IL-10 when compared to the control group (P > 0.05)., Conclusion: MTB infection induces DNA methylation changes in mo-DCs. The hypo-methylation of TNF-α may induce the up-regulation of this gene. This correlation revealed that the more resistant the MTB strain (XDR) is, the lower the methylation status (%) in the TNF-α gene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a pathogenic bacterium that has claimed millions of lives since the Middle Ages. According to the World Health Organization's report, tuberculosis ranks among the ten deadliest diseases worldwide. The presence of an extensive array of genes and diverse proteins within the cellular structure of this bacterium has provided us with a potent tool for diagnosis. While the culture method remains the gold standard for tuberculosis diagnosis, it is possible that molecular diagnostic methods, emphasis on the identification of mutation genes (e.g., rpoB and gyrA) and single nucleotide polymorphisms, could offer a safe and reliable alternative. Over the past few decades, as our understanding of molecular genetics has expanded, methods have been developed based on gene expansion and detection. These methods typically commence with DNA amplification through nucleic acid targeted techniques such as polymerase chain reaction. Various molecular compounds and diverse approaches have been employed in molecular assays. In this review, we endeavor to provide an overview of molecular assays for the diagnosis of tuberculosis with their properties (utilization, challenges, and functions). The ultimate goal is to explore the potential of replacing traditional bacterial methods with these advanced molecular diagnostic techniques., (© 2024. The Author(s).)

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii have emerged as major clinical threats owing to the increasing prevalence of ventilator-associated pneumonia caused by multidrug-resistant or extensively drug-resistant strains. The present study aimed to assess the antibacterial effects and efficacy of LL-37 fragment GF-17D3 and synthetic Scolopendin A2 peptides against resistant clinical strains in vitro and in vivo models. P. aeruginosa, S. aureus, and A. baumannii were isolated from clinical infections. Their antibiotic resistance and minimum inhibitory concentration were assessed. LL-37 fragment GF-17D3 peptide was selected from available databases. Scolopendin A2 peptide's 6th amino acid (proline) was substituted with lysine and peptides and MICs were determined. The biofilm inhibitory activity was quantified at sub MIC concentrations. Synergetic effects of Scolopendin A2 and imipenem were assessed by checkerboard. After mice nasal infection with P. aeruginosa, peptides LD50 was determined. Isolates harbored complete resistance toward the majority of antibiotics and MIC values ranged between 1 and > 512 µg/ml. The majority of isolates exhibited strong biofilm activity. Synthetic peptides showed lower MIC values than antibiotic agents and the lowest MIC values were obtained for synthetic peptides in combination with antibiotics. The Synergisms effect of Scolopendin A2 with imipenem was also determined. Scolopendin A2 was found to have antibacterial efficacy against P. aeruginosa, S. aureus, and A. baumannii with MIC 64 µg/ml, 8 µg/ml, and 16 µg/ml, respectively, and LL37 showed antibacterial efficacy against P. aeruginosa, S. aureus, and A. baumannii with MIC 128 µg/ml, 32 µg/ml, and 32 µg/ml, respectively. Both AMPs decreased biofilms by ≥ 96% at 1 × MIC. The biofilm inhibitory activity was measured at sub MIC concentrations of the peptides and the results demonstrated that Scolopendin A2 exhibited anti-biofilm activity at 1/4 × MIC and 1/2 × MIC concentrations was 47.9 to 63.8%, although LL37 among 1/4 × MIC and 1/2 × MIC concentrations was 21.3 to 49.6% against three pathogens. The combination of Scolopendin A2 and antibiotics demonstrated synergistic activity-resistant strains with FIC values ≤ 0.5 for three pathogens, while LL37 and antibiotics showed synergistic activity FIC values ≤ 0.5 for only P. aeruginosa. Infection model Scolopendin A2 with Imipenem (2 × MIC) was efficacious in vivo, with a 100% survival rate following treatment at 2 × MIC after 120 h. The mRNA expression of biofilm-related genes was decreased for both peptides. Synthesis Scolopendin A2 decreased the expression of biofilm formation genes compared to the control group. Synthetic Scolopendin A2 exhibits antimicrobial activity without causing toxicity on the human epithelial cell line. Based on our findings, it seems that synthetic Scolopendin A2 is an appropriate antimicrobial source. That could be a promising option in combination with antibiotics for a topical medication and in the prevention of acute and chronic infections caused by multidrug-resistant bacteria. Nevertheless, additional experiments are required to assess another potential of this novel AMP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Type 2 diabetes mellitus (T2DM) is considered one of the most common disorders worldwide. Although several treatment modalities have been developed, the existing interventions have not yielded the desired results. Therefore, researchers have focused on finding treatment choices with low toxicity and few adverse effects that could control T2DM efficiently. Various types of research on the role of gut microbiota in developing T2DM and its related complications have led to the growing interest in probiotic supplementation. Several properties make these organisms unique in terms of human health, including their low cost, high reliability, and good safety profile. Emerging evidence has demonstrated that three of the most important signaling pathways, including nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor erythroid 2-related factor 2 (Nrf2), which involved in the pathogenesis of T2DM, play key functions in the effects of probiotics on this disease. Hence, we will focus on the clinical applications of probiotics in the management of T2DM. Then, we will also discuss the roles of the involvement of various probiotics in the regulation of the most important signaling pathways (NF-κB, PI3K/Akt, and Nrf2) involved in the pathogenesis of T2DM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The relationship between pet and owner has already been studied in several studies. Reviewing and summarizing studies on human and pet microbiota and their effects due to keeping pets is the purpose of the current study. Microbiota of the gut, oral cavity, and skin are unique to each individual, and this is also true of their pets (cats and dogs). Microbiota homeostasis is essential for the health of pets and their owners. Dysbiosis or imbalances in the microbiota can increase the risk of disorder progressions such as IBD or Clostridium difficile infections, among others. The microbial communities of humans change as a result of various factors, such as keeping pets. Pet owners frequently contact domestic dogs and cats, which affects their microbiota. As a result of keeping pets, the microbiota of different areas of the human body has changed, which has been associated with a decrease in pathogenic bacteria and an increase in beneficial bacteria., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. No writing assistance was utilized in the production of this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Tuberculosis (TB) continues to pose a threat to communities worldwide and remains a significant public health issue in several countries. We assessed the role of heteroresistance and efflux pumps in bedaquiline (BDQ)-resistant Mycobacterium tuberculosis isolates., Methods: Nineteen clinical isolates were included in the study, of which fifteen isolates were classified as MDR or XDR, while four isolates were fully susceptible. To evaluate BDQ heteroresistance, the Microplate Alamar Blue Assay (MABA) method was employed. For screening mixed infections, MIRU-VNTR was performed on clinical isolates. Mutations in the atpE and Rv0678 genes were determined based on next-generation sequencing data. Additionally, real-time PCR was applied to assess the expression of efflux pump genes in the absence and presence of verapamil (VP)., Results: All 15 drug-resistant isolates displayed resistance to BDQ. Among the 19 total isolates, 21.05% (4/19) exhibited a heteroresistance pattern to BDQ. None of the isolates carried a mutation of the atpE and Rv0678 genes associated with BDQ resistance. Regarding the MIRU-VNTR analysis, most isolates (94.73%) showed the Beijing genotype. Fifteen (78.9%) isolates showed a significant reduction in BDQ MIC after VP treatment. The efflux pump genes of Rv0676c, Rv1258c, Rv1410c, Rv1634, Rv1819, Rv2459, Rv2846, and Rv3065 were overexpressed in the presence of BDQ., Conclusions: Our results clearly demonstrated the crucial role of heteroresistance and efflux pumps in BDQ resistance. Additionally, we established a direct link between the Rv0676c gene and BDQ resistance. The inclusion of VP significantly reduced the MIC of BDQ in both drug-susceptible and drug-resistant clinical isolates., (© 2024. The Author(s).)

The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. The results revealed that C. acnes causes memory impairment, which might be a consequence of upregulated Amyloid β (Aβ) deposits in the hippocampus; Aβ aggregates are co-localized with C. acnes colonies. The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Antibiotic resistance is a serious problem that poses a major challenge to tuberculosis control worldwide. Many developing countries still struggle with this infection in term of various aspects as it remains a major health concern. A number of developing countries are located in the Middle East, one of the world's most important regions. The control of this infection remains largely suboptimal despite intensive research in the field, and the mechanisms that lead to its progression have not yet been fully understood. Therefore, TB control must be amended through the identification of new strategies. For this reason, monitoring genetic characterizations of TB strains by molecular typing methods in different geographical regions can be important to setting local programs and global strategies to control TB infection. It is important to know the genotype of Mycobacterium tuberculosis strains to evaluate the occurrence of outbreaks and the transmission of this disease. Beijing and Haarlem genotypes are the most prevalent and, in these families, there is greater association with drug resistance, resulting in more severe forms of TB and higher levels of treatment failure than in other families. The current study is planned to systematically conduct a review using a meta-analysis to show the prevalence of Beijing and Haarlem genotypes in the Middle Eastern MDR-TB cases. M. tuberculosis strains pose particular epidemiological and clinical concerns as they can endanger tuberculosis control programs., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Burns are associated with gut dysbiosis. Collagen peptides and omega-3 fatty acids (FAs) are suggested to improve wound healing and the inflammatory response. These are also correlated with microbiome colonization. Therefore, the present study aimed to investigate the effect of hydrolyzed collagen alone or in combination with fish oil on specific species of the gut microbiome in patients with major burns. In this randomized double-blind clinical trial, 57 adults (aged 18-60 years) with 20-45% total body surface area burns were randomised into three groups to receive either 40 gr hydrolyzed collagen +10 ml sunflower oil, 40 g hydrolyzed collagen +10 ml fish oil or placebo, divided into two daily drinks, for two weeks. Gut bacteria were measured using the real-time quantitative polymerase chain reaction (qPCR) method. The mean concentration of Bifidobacterium was significantly reduced in the control (P = 0.002) and collagen (P = 0.005) groups compared with the baseline values, whereas no significant change was observed in the collagen omega-3 group. The Firmicutes to Bacteroidetes ratio decreased significantly in the collagen group (p = 0.002) after supplementation compared to baseline . No significant changes in concentration of Lactobacillus, Enterobacteriaceae, and F.prausnitzii were observed between or within the study groups. Two weeks of supplementation with collagen and omega-3 FAs in patients with major burns did not result in a significant difference in the concentration of bacteria measured between the study groups. However, the addition of omega-3 FAs prevented a significant reduction in gut Bifidobacterium. Future studies are suggested to investigate the potential efficacy of these nutrients in improving the gut microbiota and clinical outcomes in major burns. REGISTRATION NUMBER: IRCT20131125015536N9., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Introduction: There is a proven role for hepcidin and the composition of gut microbiota and its derivatives in the pathophysiology of liver fibrosis., Area Covered: This review focuses on the literature search regarding the effect of hepcidin and gut microbiota on regulating liver physiology. We presented the regulating mechanisms of hepcidin expression and discussed the possible interaction between gut microbiota and hepcidin regulation. Furthermore, we investigated the importance of the hepcidin gene in biological processes and bacterial interactions using bioinformatics analysis., Expert Opinion: One of the main features of liver fibrosis is iron accumulation in hepatic cells, including hepatocytes. This accumulation can induce an oxidative stress response, inflammation, and activation of hepatic stellate cells. Hepcidin is a crucial regulator of iron by targeting ferroportin expressed on hepatocytes, macrophages, and enterocytes. Various stimuli, such as iron load and inflammatory signals, control hepcidin regulation. Furthermore, a bidirectional relationship exists between iron and the composition and metabolic activity of gut microbiota. We explored the potential of gut microbiota to influence hepcidin expression and potentially manage liver fibrosis, as the regulation of iron metabolism plays a crucial role in this context., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Despite the fact that some cases of tuberculosis (TB) are undiagnosed and untreated, it remains a serious global public health issue. In the diagnosis, treatment, and control of latent and active TB, there may be a lack of effectiveness. An understanding of metabolic pathways can be fundamental to treat latent TB infection and active TB disease. Rather than targeting Mycobacterium tuberculosis , the control strategies aim to strengthen host responses to infection and reduce chronic inflammation by effectively enhancing host resistance to infection. The pathogenesis and progression of TB are linked to several metabolites and metabolic pathways, and they are potential targets for host-directed therapies. Additionally, metabolic pathways can contribute to the progression of lung cancer in patients with latent or active TB. A comprehensive metabolic pathway analysis is conducted to highlight lung cancer development in latent and active TB. The current study aimed to emphasize the association between metabolic pathways of tumor development in patients with latent and active TB. Health control programs around the world are compromised by TB and lung cancer due to their special epidemiological and clinical characteristics. Therefore, presenting the importance of lung cancer progression through metabolic pathways occurring upon TB infection can open new doors to improving control of TB infection and active TB disease while stressing that further evaluations are required to uncover this correlation.

Background: Non-small cell lung cancer (NSCLC) patients with COVID-19 have an excessive chance of morbidity and mortality. The fecal-nasopharyngeal microbiota compositions of NSCLC patients were assessed in this study., Methods: In total, 234 samples were collected from 17 NSCLC patients infected with COVID-19, 20 NSCLC patients without confirmed COVID-19, 40 non NSCLC patients with COVID-19, and 40 healthy individuals., Results: In lung microbiota, the abundance of Streptococcus spp. in NSCLC patients with confirmed COVID-19 was significantly higher than the two control groups. Pseudomonas aeruginosa and Staphylococcus aureus were listed as the most frequent pulmonary bacterial groups that colonized COVID-19 patients. In fecal specimens, the numbers of Bacteroidetes, Firmicutes, and Actinobacteria phyla were significantly higher amongst NSCLC patients with COVID-19. NSCLC patients infected with COVID-19 showed lower levels of Lactobacillus spp., Akkermansia muciniphila , and Bifidobacterium spp. The counts of Streptococcus spp., in NSCLC patients with COVID-19 were significantly higher than those of healthy individuals (8.49±0.70 log CFU/g wet feces vs 8.49±0.70 log CFU/g wet feces). Prevotella spp. were enriched in the gut and respiratory tracts of COVID-19 patient groups. The unbiased analysis showed an increment in Enterococcus spp., Streptococcus spp., and Prevotella spp., Conclusion: Eventually, it was found that compared to control groups, COVID-19 patients with NSCLC showed diminished gut bacteria diversity and increase in Lactobacillus spp ., A. muciniphila , and Bifidobacterium spp. The overgrowth of Enterococcus spp., Streptococcus spp., and Prevotella spp. could be potential predictive biomarkers in the gut-lung axis of NSCLC patients with COVID-19., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Purpose: Cardiometabolic disease (CMD) is increasing along with its predisposing factors and adverse consequences. As gut microbiota dysbiosis is established in these patients, fecal microbiota transplantation (FMT), which alters the bacterial composition of the intestine, supposedly can help improve cardiometabolic disturbances. We conducted a systematic review and meta-analysis evaluating the impact of FMT on the cardiometabolic parameters and gut microbiota composition of patients experiencing at least one cardiometabolic issue., Methods: Eligible studies were searched through the PubMed, Web of Science, and Scopus databases until December 2022. The initial search results underwent duplication removal and screening until each included study was scanned for intended data. The Cochrane risk of bias tool was used to evaluate the methodologic accuracy of studies and the random effects model was used for conducting the meta-analysis., Findings: Eighteen of the original 2414 articles from the literature search were entered into the systematic review; of these, 11 were included in the meta-analysis. Insulin showed a significant decrease by 24.7 pmol/L (weighted mean difference [WMD], -24.77; 95% CI, -48.704 to -0.848) after short-term follow-up, and HDL increased by 0.1 mmol/l(WMD, 0.106; 95% CI, 0.027 to 0.184) and 0.12 mmol/l(WMD, 0.120; 95% CI, 0.003 to 0.237) in those using a capsule deliver mode and in short-term follow-up, respectively. No significant changes were seen in other lipid profiles, blood glucose, insulin resistance, or anthropometric indices. In addition, multiple studies reported gut microbiota alterations after the intervention, including an increase in butyrate-producing species., Implications: Although some articles reported the beneficial effects of FMT on metabolic parameters, we failed to find a clinically significant alteration. Also, information regarding proper donors and the best method to induce FMT have not yet been sufficiently investigated, which should be considered along with means to prevent potential damages. PROSPERO identifier: CRD42022380705., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Tuberculosis (TB) has been a major health issue throughout history. As part of TB infection, host- Mycobacterium tuberculos is (Mtb) interactions are important. Through immune pathology and cell death control processes, Mtb infection facilitates intracellular growth. The relationship between apoptosis and inflammation in Mtb infection remains unclear. In this study, the levels of related apoptosis and inflammatory genes were assessed in A549 cells infected with a variety of Mtb strains., Materials and Methods: Mtb isolates with different phenotypes (sensitive, INH R , Rif R , MDR, and XDR) were collected from the Pasteur Institute of Iran, during this study. Whole genome sequencing was previously performed on all strains, and the Beijing genotype was selected as sensitive. Also, for other resistant strains, the New-1 genotype was available and isolated for genotype comparison. A549 lung carcinoma cells were also grown and infected with selected Mtb strains. Genes involved in inflammation and apoptosis were detected using reverse transcription-PCR (RT-PCR)., Results: All sensitive strains and resistant strains were found to significantly up-regulate anti-apoptotic ( bcl2 and rb1 ), chemokine ( IL-8 and MCP-1 ), and pro-inflammatory cytokine ( TNF- α and IFN- γ ) expression, while significant down-regulation was observed after 24 and 48 hr of infection in anti-inflammatory genes (IL-10) and pro-apoptotic genes (bad and bax). Besides resistance strains, Mtb genotypes also affected gene expression. The Beijing genotype (sensitive isolate) influences inflammatory and apoptotic genes more sharply than the New-1 genotype (INH R , Rif R , MDR, and XDR)., Conclusion: Gene expression differences related to apoptosis and inflammation examined in the current study may be attributed to genotypes rather than resistance status since the expression of most genes has been observed to be lower in resistant strains (INH R , Rif R , MDR, and XDR belonging to the New-1 genotype) compared to sensitive strains (Beijing genotype)., Competing Interests: The authors declare that no conflict of interest exists.

Purpose: When examining the underlying processes of obesity, evaluation of gut flora and energy homeostasis can be crucial since disruption of the normal gut microbiota community and energy imbalances are significant factors in the development of obesity. Therefore, this study aimed to compare the relative abundance of important obesity modulator gut microbiota (including Firmicutes, Bacteroidetes, Bifidobactrium spp. , Lactobacillus spp. , Bacteroides fragilis , Faecalibacterium prausnitzii , Akkermansia muciniphila , and Escherichia coli ) in fecal samples of normometabilic and hypometabolic overweight/obese individuals., Methods: This matched case-control study conducted on 36 healthy women aged 18-50 years old. An indirect calorimeter and impedance body analyzer were used to assess resting metabolic rate (RMR) and body composition, respectively. Dietary intake and physical activity were assessed using questionnaires. To determine the abundance of the abovementioned gut microbiota, quantitative polymerase chain reaction (qPCR) method was performed. Moreover, ELISA kits were used to assess leptin, ghrelin, and insulin hormones., Results: The results highlighted higher load of Firmicutes ( p  = 0.02), F. prausnitzii ( p  < 0.001), and B. fragilis ( p  = 0.02) in the normometabolic individuals compared to the hypometabolic ones. Besides, the positive correlation between the abundance of Firmicutes (β = 7.76 × 10 -1 , p  = 0.01), F. prausnitzii (β = 1.29 × 10 -5 , p  = 0.01), and B. fragilis (β = 4.13 × 10 -6 , p  = 0.04) with the RMR have been shown. Whereas the abundance of Bacteroidetes, A. muciniphila , Lactobacillus spp. , Bifidobactrium spp. , and E. coli showed no significant difference ( p  > 0.05) and no significant correlation with the RMR except Lactobacillus spp. (β = 1.73 × 10 -4 , p  = 0.01)., Conclusion: It seems that gut microbiota can be a potential target for refining host energy homeostasis and treating obesity and its consequences., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b)., Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs., Results: Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f down-regulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348)., Conclusion: Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection., (Copyright © 2023 The Authors. Published by Tehran University of Medical Sciences.)

Objectives: A better understanding of host-microbe interactions as a cross-talk between the gastrointestinal (GI) tract and the gut microbiota can help treat and prevent GI disorders by improving the maintenance of GI homeostasis. The gut microbiota can affect signaling molecules, such as serotonin, which regulates endocrine systems through the GI tract. Moreover, studying the effects of gut microbiota in the small intestine on the human GI tract health is pivotal., Methods: Male C57BL/6J mice (n = 30, 10 mice per group) were orally gavaged with 200 μL of PBS (control group); mice in group II were orally gavaged with 109 colony-forming units (CFU)/200 μL of viable A. muciniphila, suspended in PBS (A. muciniphila group); and mice in group III were orally gavaged with 10 μg of protein/200 μL of EVs (A. muciniphila-EV group) once daily for four weeks. The gene expression of serotonin system-related genes (Slc6a4, Tph1, Mao, Htr3, Htr4, and Htr7) was examined by quantitative real-time PCR (qPCR) method., Results: Based on the results, A. muciniphila significantly affected the mRNA expression of genes related to the serotonin system (Tph1, Mao, Htr3B, and Htr7) in the duodenum and (Htr3B, Htr4 and Htr7) in the ileum of mice (P < 0.05). Moreover, A. muciniphila-derived EVs affected the expression of major genes related to the serotonin system (Tph1, slc6a4a, Mao, Htr3B, Htr4, and Htr7) in the duodenum and ileum of mice (P < 0.05)., Conclusions: The present findings may pave the way for further investigation of the effects of strain-specific probiotics on the serotonergic system, which is currently in its infancy., Competing Interests: Declaration of competing interest The authors declare no competing both financial and non-financial interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The human gut microbiota plays a crucial role in mental health through the gut-brain axis, impacting central nervous system functions, behavior, mood, and anxiety. Consequently, it is implicated in the development of neuropsychiatric disorders. This study aimed to assess and compare the gut microbiota profiles and populations of individuals with bipolar disorder and healthy individuals in Iran., Methods: Fecal samples were collected from 60 participants, including 30 bipolar patients (BPs) and 30 healthy controls (HCs), following rigorous entry criteria. Real-time quantitative PCR was utilized to evaluate the abundance of 10 bacterial genera/species and five bacterial phyla., Results: Notably, Actinobacteria and Lactobacillus exhibited the greatest fold change in BPs compared to HCs at the phylum and genus level, respectively, among the bacteria with significant population differences. Ruminococcus emerged as the most abundant genus in both groups, while Proteobacteria and Bacteroidetes showed the highest abundance in BPs and HCs, respectively, at the phylum level. Importantly, our investigation revealed a lower Firmicutes/Bacteroidetes ratio, potentially serving as a health indicator, in HCs compared to BPs., Conclusion: This study marks the first examination of an Iranian population and provides compelling evidence of significant differences in gut microbiota composition between BPs and HCs, suggesting a potential link between brain functions and the gut microbial profile and population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rashnaei, Akhavan Sepahi, Siadat, Shahsavand-Ananloo and Bahramali.)

Background: Tuberculosis (TB) is a communicable disease that is a major cause of death and one of the leading causes of death worldwide. Currently, there is no analyzed data to examine the financial profile of TB by country, continent, and year; this article analyzed TB prevention, diagnosis, and treatment financial profile during the last two decades., Methods: Original research, reviews, and governmental databases are analyzed to present the financial profile of TB., Results: Analyzed data showed Europe (23137.133), Asia (20137.073), and Africa (15237.973) had the most allocated funds (US $ million), and Oceania (236.702), and America (4745.043) had the lowest allocated fund (US $ million) during 2006-2021. Additionally, the allocation of funds (domestic funds, global funds, and grants [excluding global funds]) in different countries and proper planning for TB eradication has caused that in the last two decades, the slope of the confirmed cases and deaths graph line is negative., Conclusion: The number of confirmed cases and deaths reported globally is decreasing. The trend lines showed that the assigned funds are increasing, indicating that the TB eradication plan can be apprehended soon., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Gut microbiota and its derivatives by constantly interacting with the host, regulate the host function. Intestinal epithelium integrity is under the control of various factors including the endocannabinoid system (ECS). Accordingly, we aimed at investigating the effect of Bacteroides fragilis and its postbiotics (i.e., heat-inactivated, cell-free supernatants (CFS) and outer membrane vesicles (OMVs)) on the expression of genes involved in ECS ( cnr1, faah, pparg ) and the epithelial barrier permeability ( ocln, tjp1 ) in a Caco-2 cell line., Methods: Caco-2 cell line was treated with live or heat-inactivated B. fragilis at MOIs of 50 and 100, or stimulated with 7% V/V CFS and B. fragilis OMVs at a dose of 50 and 100 µg/ml overnight. RT-qPCR was applied for expression analysis., Results: Heat-inactivated B. fragilis induced cnr1, pparg , tjp1 , and suppressed faah expression, while live B. fragilis had the opposite effect. OMVs increased pparg , and tjp1 expression by reducing the activity of ECS through an increase in faah and a reduction in cnr1 expression. Finally, an increase in the expression of pparg and ocln , and a reduction in the expression of cnr1 was detected in Caco-2 cells treated with CFS., Conclusion: The live and heat-inactivated B. fragilis inversely affected cnr1 , faah , pparg , and tjp1 expression in Caco-2 cells. Increased tjp1 mRNA levels by affecting the expression of ECS related genes is taken as an indication of the potential beneficial effects of B. fragilis postbiotics and making them potential candidates for improving permeability in the leaky gut syndrome., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01264-8., Competing Interests: Competing interestsThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background & Objective: Streptococcus pneumoniae , Haemophilus influenzae and Streptococcus pyogenes are among the most important causes of infection in human. Inventing rapid methods to identify these species can help in providing appropriate and effective treatment options. Therefore, the current study aimed to develop a multiplex touch-down PCR method to identify rapidly the aforementioned species patients' sputum samples, simultaneously., Methods: A total of 50 sputum samples of patients with respiratory infections resistant to treatment were collected. After DNA extraction and primer design, the complete capsule (CAP) region II, capsular polysaccharide biosynthesis (cpsA) and the structural regulator of transcription (spy) genes were amplified for detecting H. influenzae , S. pneumoniae and S. pyogenes by multiplex touch-down PCR., Results: Among 50 samples prepared from patients with different diseases, 27 samples were positive for amplified genes. The frequency of presence of pathogens in the collected samples included 14% H. influenzae , 20% S. pneumoniae and 20% S. pyogenes . Also, in some patients, the simultaneous presence of two or three pathogens were observed., Conclusion: In general, it can be concluded that the PCR touchdown method developed in the present study is an effective and fast method for the simultaneous identification of H. influenzae , S. pneumoniae and S. pyogenes pathogens in clinical samples of patients., Competing Interests: There is no conflict of interest among authors.

Klebsiella spp. is a commensal gram-negative bacterium and a member of the human microbiota. It is the leading cause of various hospital-acquired infections. The occurrence of multi-drug drug resistance and carbapenemase-producing strains of Klebsiella pneumoniae producing weighty contaminations is growing, and Klebsiella oxytoca is an arising bacterium. Alternative approaches to tackle contaminations led by these microorganisms are necessary as strains enhance opposing to last-stage antibiotics in the way that Colistin. The lytic bacteriophages are viruses that infect and rapidly eradicate bacterial cells and are strain-specific to their hosts. They and their proteins are immediately deliberate as opportunities or adjuncts to antibiotic therapy. There are several reports in vitro and in vivo form that proved the potential use of lytic phages to combat superbug stains of K. pneumoniae. Various reports dedicated that the phage area can be returned to the elimination of multi-drug resistance and carbapenemase resistance isolates of K. pneumoniae. This review compiles our current information on phages of Klebsiella spp. and highlights technological and biological issues related to the evolution of phage-based therapies targeting these bacterial hosts., (© 2023. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

It is a growing problem around the world to deal with nontuberculous mycobacteria infection (NTM), but its clinical significance is still largely unknown. This study aims to investigate the epidemiology of NTM infections from various clinical samples and determine their clinical significance. From December 2020 to December 2021, 6125 clinical samples were collected. In addition to phenotypic detection, genotypic detection through multilocus sequence typing (hsp65, rpoB, and 16S rDNA genes) and sequencing was also conducted. Records of patients were consulted for clinical information, such as symptoms and radiological findings. Of the 6,125 patients, 351 (5.7%) were positive for acid-fast bacteria (AFB). Out of 351 AFB, 289 (82.3%) and 62 (17.7%) subjects were identified as M. tuberculosis complex (MTC) and NTM strains, respectively. Isolates of Mycobacterium simiae and M. fortuitum were the most frequent, followed by isolates of M. kansasii and M. marinum. We also isolated M. chelonae, M. canariasense, and M. jacuzzii, which are rarely reported. Symptoms (P = 0.048), radiographic findings (P = 0.013), and gender (P = 0.039) were associated with NTM isolates. M. Fortuitum, M. simiae, and M. kansasii presented with bronchiectasis, infiltration, and cavitary lesions most frequently, while cough was the most common symptom. In conclusion, Mycobacterium simiae and M. fortuitum were presented in seventeen and twelve NTM isolates from the collected samples. There is evidence that NTM infections in endemic settings may contribute to the dissemination of various diseases and the control of tuberculosis. In spite of this, further research is needed to evaluate the clinical significance of NTM isolates., (© 2023. The Author(s).)

Purpose: Metabolic syndrome (MetS) is a major public health concern that increases the risk of cardiovascular disease and mortality. In previous studies of MetS management, low-carbohydrate diets have been strongly emphasized, despite the fact that many apparently healthy individuals have difficulties adhering to these diets on a long-term basis. The purpose of the present study was to elucidate the effects of a moderately restricted carbohydrate diet (MRCD) on cardiometabolic risk factors in women with MetS., Methods: This parallel 3-month, single-blind randomized controlled trial was conducted in Tehran, Iran, among 70 women with overweight or obesity aged 20 to 50 years with MetS. Patients were randomly allocated to receive either MRCD (42%-45% carbohydrates and 35%-40% fats) (n = 35) or a normal weight loss diet (NWLD) (52%-55% carbohydrates and 25%-30% fats) (n = 35). Both diets contained the same quantity of protein, which accounted for 15% to 17% of total energy. Anthropometric measurements, blood pressure, lipid profile, and glycemic indices were all assessed before and after the intervention., Findings: Compared with the NWLD group, following an MRCD significantly decreased weight (-4.82 vs -2.40 kg; P = 0.01), body mass index (-1.88 vs -0.94 kg/m 2 ; P = 0.01), waist circumference (-5.34 vs -2.75 cm; P = 0.01), hip circumference (-2.58 vs -1.11 cm; P = 0.01), serum triglyceride (-26.8 vs -7.19 mg/dL; P = 0.01), and increased serum HDL-C levels (1.89 vs. 0.24 mg/dL; P = 0.01). There was no significant difference between the 2 diets in waist-to-hip ratio, serum total cholesterol, serum LDL-C, systolic and diastolic blood pressure, fasting blood glucose, insulin levels, or the homeostasis model assessment for insulin resistance., Implications: Moderate carbohydrate replacement with dietary fats significantly improved weight, body mass index, waist circumference, hip circumference, serum triglyceride, and HDL-C levels among women with MetS. Iranian Registry of Clinical Trials identifier: IRCT20210307050621N1., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant clinical problem, given the lack of therapeutic options. The CRKP strains have emerged as an essential worldwide healthcare issue during the last 10 years. Global expansion of the CRKP has made it a significant public health hazard. We must consider to novel therapeutic techniques. Bacteriophages are potent restorative cases against infections with multiple drug-resistant bacteria. The Phages offer promising prospects for the treatment of CRKP infections., Objective: In this study, a novel K. pneumoniae phage vB&#95;KshKPC-M was isolated, characterized, and sequenced, which was able to infect and lyse Carbapenem-resistant K. pneumoniae host specifically., Methods: One hundred clinical isolates of K. pneumoniae were collected from patients with COVID-19 associated with ventilator-associated acute pneumonia hospitalized at Shahid Beheshti Hospital, Kashan, Iran, from 2020 to 2021. Initially, all samples were cultured, and bacterial isolates identified by conventional biochemical tests, and then the ureD gene was used by PCR to confirm the isolates. The Antibiotic susceptibility test in the disc diffusion method and Minimum inhibitory concentrations for Colistin was done and interpreted according to guidelines. Phenotypic and molecular methods determined the Carbapenem resistance of isolates. The blaKPC, blaNDM, and blaOXA-23 genes were amplified for this detection. Biofilm determination of CRKP isolates was performed using a quantitative microtiter plate (MTP) method. The phage was isolated from wastewater during the summer season at a specific position from Beheshti Hospital (Kashan, Iran). The sample was processed and purified against the bacterial host, a CRKP strain isolated from a patient suffering from COVID-19 pneumoniae and resistance to Colistin with high potency for biofilm production. This isolate is called Kp100. The separated phages were diluted and titration by the double overlay agar plaque assay. The separate Phage is concentrated with 10% PEG and stored at -80 °C until use. The phage host range was identified by the spot test method. The purified phage morphology was determined using a transmission electron microscope. The phage stability tests (pH and temperature) were analyzed. The effect of cationic ions on phage adsorption was evaluated. The optimal titer of bacteriophage was determined to reduce the concentration of the CRKP strain. One-step growth assays were performed to identify the purified phage burst's latent cycle and size. The SDS-PAGE was used for phage proteins analysis. Phage DNA was extracted by chloroform technique, and the whole genome of lytic phage was sequenced using Illumina HiSeq technology (Illumina, San Diego, CA). For quality assurance and preprocessing, such as trimming, Geneious Prime 2021.2.2 and Spades 3.9.0. The whole genome sequence of the lytic phage is linked to the GenBank database accession number. RASTtk-v1.073 was used to predict and annotate the ORFs. Prediction of ORF was performed using PHASTER software. ResFinder is used to assess the presence of antimicrobial resistance and virulence genes in the genome. The tRNAs can-SE v2.0.6 is used to determine the presence of tRNA in the genome. Linear genome comparisons of phages and visualization of coding regions were performed using Easyfig 2.2.3 and Mauve 2.4.0. Phage lifestyles were predicted using the program PHACTS. Phylogenetic analysis and amino acid sequences of phage core proteins, such as the major capsid protein. Phylogenies were reconstructed using the Neighbor-Joining method with 1000 bootstrap repeat. HHpred software was used to predict depolymerase. In this study, GraphPad Prism version 9.1 was used for the statistical analysis. Student's t-test was used to compare the sets and the control sets, and the significance level was set at P ≤ 0.05., Results: Phage vB&#95;KshKPC-M is assigned to the Siphoviridae, order Caudovirales. It was identified as a linear double-stranded DNA phage of 54,378 bp with 50.08% G + C content, had a relatively broad host range (97.7%), a short latency of 20 min, and a high burst size of 260 PFU/cell, and was maintained stable at different pH (3-11) and temperature (45-65 °C). The vB&#95;KshKPC-M genome contains 91 open-reading frames. No tRNA, antibiotic resistance, toxin, virulence-related genes, or lysogen-forming gene clusters were detected in the phage genome. Comparative genomic analysis revealed that phage vB&#95;KshKPC-M has sequence similarity to the Klebsiella phages, phage 13 (NC&#95;049844.1), phage Sushi (NC&#95;028774.1), phage vB&#95;KpnD&#95;PeteCarol (OL539448.1) and phage PWKp14 (MZ634345.1)., Conclusion: The broad host range and antibacterial activity make it a promising candidate for future phage therapy applications. The isolated phage was able to lyse most of the antibiotic-resistant clinical isolates. Therefore, this phage can be used alone or as a phage mixture in future studies to control and inhibit respiratory infections caused by these bacteria, especially in treating respiratory infections caused by resistant strains in sick patients., (© 2023. The Author(s).)

Aim: Fresh evidence suggests that B. coagulans can be regarded as a promising therapeutic alternative for metabolic disorders. However, the possible effects of this probiotic on obesity-induced adipose tissue inflammation are unknown., Methods: C57BL/6j male mice were assigned to a normal-chow diet (NCD) or a high-fat diet (HFD) for 10 weeks. After this period, HFD-fed mice were randomly divided into two groups; HFD control group and HFD plus B. coagulans T4 (IBRC-N10791) for another 8 weeks. B. coagulans T4 was administrated daily by oral intragastric gavage (1 × 10 9 colony-forming units)., Key Findings: Here, we found that B. coagulans successfully mitigated obesity and related metabolic disorder, as indicated by reduced body weight gain, decreased adiposity, and improved glucose tolerance. B. coagulans T4 administration also inhibited HFD-induced macrophage accumulation in white adipose tissue and switched M1 to M2 macrophages. In parallel, B. coagulans T4 treatment attenuated HFD-induced alteration in mRNA expression of pro/anti-inflammatory cytokines and Tlr4 in white adipose tissue. Moreover, B. coagulans T4 supplementation reduced the Firmicutes/Bacteriodetes ratio and increased the number of Lactobacillus and Faecalibacterium compared to the HFD group. Additionally, a significant increase in propionate and acetate levels in the HFD group was seen following B. coagulans T4 administration., Significance: Taken together, the present study provides evidence that B. coagulans T4 supplementation exerts anti-obesity effects in part through attenuating inflammation in adipose tissue. The present study will have significant implications for obesity management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Obesity in the older adults is a health concern that increases the risk of several life-threatening diseases. Previous research has been revealed that alterations in the gut microbiota composition is related to obesity. So, understanding the gut microbiota changes in older adults' obesity may help to provide promising strategies for their health management., Objectives: Here we conducted a systematic review that investigate the alteration of gut microbiota composition in association with obesity and its indices in the older adults., Design: Systematic review., Setting: A comprehensive systematic search was performed through PubMed, Web of Science, Scopus and Embase databases for all relative studies up to 2023 with the main search concepts as Microbiota, Obesity and Elderly. The data about gut microbiota in association with obesity indices had been extracted., Participants: Older adults (≥60 years)., Intervention: None., Measurements: None., Results: Within 10741 recordes, 11 studies met the inclusion criteria and were included in this systematic review. Most of them indicated the gut microbiota alterations in obese compared with non-obese older adults. However, the gut microbiome composition in obese older adults is affected by other underlying diseases like diabetes and metabolic syndrome. The most important taxa that had abundance alteration in association with obesity in older adults were Christensenellaceae, Porphyromonadaceae and Rikenellaceae, Akkermansia, Blautia, Prevotella, Ruminococcus, Bacteroides and Faecalibacterium., Conclusion: The gut microbiota composition is associated with obesity in older adults. Considering the other factors affecting the composition of gut microbiota, such as age, underlying diseases and lifestyle, a more accurate conclusion about this matter requires more future studies., Competing Interests: The authors declare no conflict of interest, financial or otherwise.

Background: Two newly identified proteins, EspB and EspC are involved in the pathogenesis of Mycobacterium tuberculosis . The objective of the present study was to evaluate the immunogenicity of recombinant EspC, EspB, and EspC/EspB fusion proteins in mice., Methods: BALB/c mice were immunized subcutaneously with recombinant EspC, EspB, and fusion EspC/EspB proteins, three times with along with Quil-A as an adjuvant. The cellular and humoral immune responses were evaluated by quantifying IFN-γ, IL-4, IgG, IgG1, and IgG2a antibodies against the antigens., Results: The results showed that the mice immunized with recombinant EspC, EspB, and EspC/EspB proteins did not produce IL-4, whereas IFN-γ was secreted in response to all three proteins. EspC/EspB group produced significant amounts of IFN-γ in response to stimulation with all the three recombinant proteins (P<0.001). In mice immunized with EspC, high levels of IFN-γ were detected in response to EspC/EspB, and EspC (P<0.0001); while mice immunized with EspB produced lower levels of IFN-γ in response to EspC/EspB, and EspB (P<0.05).Mice immunized with recombinant EspC, EspB, and EspC/EspB proteins exhibited significantly high levels of IgG and IgG2a/IgG1 ratio (P< 0.001). Moreover, high levels of IgG and IgG2a were detected in the sera of mice immunized with EspC/EspB fusion protein., Conclusions: All the three recombinant proteins induced Th1-type immune responses in mice against EspB and EspC; however, EspC/EspB protein is more desirable due to the presence of epitopes from both EspC and EspB proteins and the production of immune responses against both., Competing Interests: The authors declare that there are no conflicts of interest.

Pseudomonas aeruginosa is an opportunistic pathogen considered a common cause of nosocomial infection with high morbidity and mortality in burn patients. Immunoprophylaxis techniques may lower the mortality rate of patients with burn wounds infected by P. aeruginosa; consequently, this may be an efficient strategy to manage infections caused by this bacterium. Several pathogenic Gram-negative bacteria like P. aeruginosa release outer membrane vesicles (OMVs), and structurally OMV consists of several antigenic components capable of generating a wide range of immune responses. Here, we evaluated the immunogenicity and efficacy of P. aeruginosa PA-OMVs (PA-OMVs) conjugated with the diphtheria toxoid (DT) formulated with alum adjuvant (PA-OMVs-DT + adj) in a mice model of burn wound infection. ELISA results showed that in the group of mice immunized with PA-OMVs-DT + adj conjugated, there was a significant increase in specific antibodies titer compared to non-conjugated PA-OMVs or control groups. In addition, the vaccination of mice with PA-OMVs-DT + adj conjugated generated greater protective effectiveness, as seen by lower bacterial loads, and eightfold decreased inflammatory cell infiltration with less tissue damage in the mice burn model compared to the control group. The opsonophagocytic killing results confirmed that humoral immune response might be critical for PA-OMVs mediated protection. These findings suggest that PA-OMV-DT conjugated might be used as a new vaccine against P. aeruginosa in burn wound infection., (© 2022. The Author(s).)

BK polyomavirus (BKPyV) is a well-known cause of nephropathy in renal transplant recipients. It has recently received much attention from researchers as a major predisposing factor for various cancers. This study aimed to investigate how BKPyV affected the advancement of papillary thyroid carcinoma (PTC). A total of 1057 samples were tested for BKPyV DNA and RNA, comprising 645 paraffin-embedded PTC biopsy samples (PEBS), 412 fresh biopsy samples (FBS), and 1057 adjacent noncancerous samples. The BKPyV DNA was found in 511 (48.3%) of the specimens, including 347 (84.2%) FBS and 164 (25.4%) PEBS. The mean BKPyV copy number was significantly lower in patients with PEBS (0.5 × 10 -4  ± 0.1 × 10 -4  copies/cell) than in FBS (1.3 × 10 -1  ± 0.2 × 10 -1  copies/cell) and non-PTC normal samples (0.3 × 10 -5  ± 0.04 × 10 -5  copies/cell). The PEBS had lower LT-Ag RNA expression than FBS, and no VP1 gene transcript expression was detected. In conclusion, although our findings indicated the presence of BKPyV in some Iranian PTC patients, more research is needed to corroborate these findings., (© 2022 Wiley Periodicals LLC.)

Introduction: Coronavirus disease-2019 (COVID-19) is a complex infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause also gastrointestinal symptoms. There are various factors that determine the host susceptibility and severity of infection, including the renin-angiotensin system, the immune response, and the gut microbiota. In this regard, we aimed to investigate the gene expression of ACE, AGTR1, ACE2, and TMPRSS2, which mediate SARS-CoV-2 pathogenesis by Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis on Caco-2 cells. Also, the enrichment analysis considering the studied genes was analyzed on raw data from the microarray analysis of COVID-19 patients., Materials and Methods: Caco-2 cells were treated with live, heat-inactivated form and cell free supernatants of A. muciniphila, F. prausnitzii, B. thetaiotaomicron and B. fragilis for overnight. After RNA extraction and cDNA synthesis, the expression of studied genes was assessed by RT-qPCR. DNA methylation of studied genes was analyzed by Partek® Genomics Suite® software on the GSE174818 dataset. We used GSE164805 and GSE166552 datasets from COVID-19 patients to perform enrichment analysis by considering the mentioned genes via GEO2R, DAVID. Finally, the related microRNAs to GO terms concerned on the studied genes were identified by miRPath., Results: The downregulation of ACE, AGTR1, and ACE2 genes by A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis in live, heat-inactivated, and cell-free supernatants was reported for the first time. These genes had hypomethylated DNA status in COVID-19 patients' raw data. The highest fold enrichment in upregulated RAS pathways and immune responses belonged to ACE, AGTR1, and ACE2 by considering the protein-protein interaction network. The common miRNAs targeting the studied genes were reported as miR-124-3p and miR-26b-5p., Conclusion: In combination with our experimental data and bioinformatic analysis, we showed the potential of A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis and their postbiotics to reduce ACE, ATR1, and ACE2 expression, which are essential genes that drive upregulated biological processes in COVID-19 patients. Accordingly, due to the potential of studied bacteria on the alteration of ACE, AGTR1, ACE2 genes expression, understanding their correlation with demonstrated miRNAs expression could be valuable. These findings suggest the importance of considering targeted gut microbiota intervention when designing the possible therapeutic strategy for controlling the COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Metabolic syndrome (MetS) is a group of risk factors that increase the risk of death and a variety of chronic diseases. Recent studies have indicated that the imbalance of gut microbiota might contribute to development and progression of metabolic syndrome. Carbohydrate restriction in the diet has been proven to be one of the most effective methods in the management of metabolic syndrome, even in the absence of weight loss. However, no study has examined the effects of a carbohydrate-restricted diet on gut microbiota composition in metabolic syndrome patients. Thus, we will examine the effects of a "moderately restricted carbohydrate (MRC)" diet on gut microbiota, insulin resistance, and components of MetS among Iranian women. In addition, the stability of changes in dependent variables, including gut microbiota, will also be assessed., Methods: This is a parallel randomized clinical trial in which 70 overweight or obese women aged 20-50 years with MetS will be randomly assigned to receive either MRC diet (42-45% carbohydrate, 35-40% fats) or a normal weight loss (NWL) diet (52-55% carbohydrate, 25-30% fats) for 3 months. Protein accounted for 15-17% of total energy in both diets. The quantity of gut microbiota including Firmicutes, Bacteroidetes, Bifidobacteria, Lactobacillus, Clostridium, Prevotella, Bacteroidetes, and Akkermansia muciniphila, as well as anthropometric, blood pressure, and metabolic parameters will be measured at study baseline and the end of trail. At the end of this phase, all participants will be placed on a weight maintenance diet for an additional 6 months. After following up study subjects in this duration, all dependent variables will be examined again to assess their stability over this period., Discussion: To the best of our knowledge, this is the first randomized controlled trial investigating the effects of a moderately restricted carbohydrate diet on gut microbiota composition and several metabolic parameters during the weight loss and maintenance phases in women with MetS., Trial Registration: Iranian Registry of Clinical Trials ( www.irct.ir , IRCT20210307050621N1). Registered on May 31, 2021., (© 2022. The Author(s).)