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Background and Objective: Vancomycin is used for treatment of methicillin-resistant S. Aureus (MRSA) infections; therefore, resistance to this antibiotic is increasing. We aimed to determine the antibiotic resistance pattern and frequency of vancomycin resistant S. Areas (VRSA) strains isolated from clinical samples. Material and Methods: In this cross-sectional study, 100 S. Aureus isolates collected from hospitals in Shiraz during six months, 2012, were identified by biochemical, microbiological and molecular methods. After determination of antibiotic susceptibility pattern by disc diffusion method and vancomycin agar screening test, Minimum Inhibitory Concentration (MIC) was determined by E-test for vancomycin, thicoplanin, linezolid and quinupristin-dalfopristin. Results: The most resistant and the most sensitive antibiotic were ampicillin (%95) and quinupristin-dalfopristin (99%), respectively, and 44% of isolates were resistant to methicillin. In agar screening test, 48% of strains had reduced sensitivity and in disc diffusion 3% strains were resistant to vancomycin. In E-test method, only one isolate was resistant to vancomycin. Conclusion: given the presence of VRSA and new antibiotic resistant strains, we recommend doing some intervention to prevent from spreading these strains in hospitals. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) is now the primary diagnostic method for head trauma because of its ability to demonstrate the nature, extent, sites, and multiplicity of brain injuries. Although there have been numerous reports on the CT findings of most types of intracranial injury, the findings in brainstem injury have not been well described. This study aimed at comparing the autopsy findings of brainstem in head trauma in comparison with CT scan results. Two hundred patients with head trauma, who expired after a period of time of hospitalization, were assessed in a diagnostic value study. Brain stem involvement was determined by autopsy as well as CT scanning of the brain during their hospitalization. The results of the two methods were compared with each other, emphasizing on the type and location of probable lesions in the brain stem. Considering the autopsy as the method of the choice, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT scan in brain stem lesions of patients with head trauma were calculated. The effect of primary cause of head trauma, survival time and Glasgow Coma Scale (GCS) were evaluated, as well. Brain stem lesions were detected in 39 (19.5%) patients in autopsy. However, CT scan revealed brain stem lesions in 23(11.5%) cases. The sensitivity, specificity, PPV and NPV of CT scan was 59%, 100%, 100% and 91% respectively. The most common lesions of the brain stem region were as contusion of pons (8.5%), medulla (5%) and midbrain (4.5%). There were 6 (3%) cases of ponto-medullary junction tearing and 1 (0.5%) case of cervico-medullary junction tearing. CT scan is a specific method of evaluating patients with probable brain stem injuries after head trauma, but low sensitivity limits its efficacy. Our results are in conformity with the reports in the literature.

Background: Given the limited available data about to the number of vaccine doses administered over an extended time in Iran, the immune status of vaccinated individuals and any potential disparities in this regard among those who received different numbers of vaccine doses remain unknown. Therefore, this study aimed to assess humoral immunity of individuals who received different doses of the COVID-19 vaccines in Iran., Methods: This study was conducted from February, 2022 to December 2023 including 605 vaccinated subjects. The durability of anti-spike, anti-nucleocapsid (NCP), neutralizing antibody, and interferon-γ (IFN-γ) was evaluated at least 6 months after the last vaccination, as well as 60 and 120 days after it, in individuals who received two or three doses of the COVID-19 vaccine. Furthermore, the evaluation of humoral and cellular response was performed before the fourth dose (second booster) as well as 21 and 60 days thereafter., Results: The 3-dose group showed significantly higher levels of anti-spike, neutralizing antibodies, and IFN-γ compared to the 2-dose group. Both the 2-dose and 3-dose groups experienced a slight decrease in the dynamic of SARS-CoV-2 Abs, though the associated levels remained within a positive range. After receiving the fourth dose of PastoCovac, most participants had significantly high levels of anti-spike, neutralizing antibodies, and IFN-γ, regardless of the type of three-dose regimen they had previously received. The average antibody titer decreased after 60 days from the fourth dose, but remained relatively stable during the follow-up period., Conclusion: This study found that the level of anti-SARS-CoV-2 antibodies and IFN-γ, as well as their durability, were still within a positive range in 2-dose and 3-dose vaccinated groups over the long-term follow-up. Furthermore, PastoCovac vaccine enhanced humoral and cellular immune responses and could be recommended as a booster dose for individuals previously vaccinated with any previously administered COVID-19 vaccine., 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 © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The coronavirus disease of 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can alter the expression levels of host microRNAs (miRNAs). Increasing evidence suggests that circulating miRNAs can potentially play an important role in the diagnosis and prognosis of respiratory infectious diseases, especially COVID-19, and might serve as sensitive indicators of disease before the emergence of clinical symptoms. Here, we review the potential of circulatory microRNAs as novel biomarkers for different aspects of COVID-19. Recent studies have suggested that they can be useful not only for COVID-19 prognosis but also for prediction of disease severity and mortality among intensive care unit (ICU) and ward patients. Moreover, extracellular vesicle (EV) miRNAs can be associated with antibody titer after COVID-19 vaccination. This review provides an overview of miRNA-based biomarkers., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest regarding the publication of this article., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

During COVID-19 pandemic, international pharmaceutical companies put effort to build global manufacturing networks for vaccines. Soberana Plus vaccine, a recombinant protein based vaccine (RBD dimer), with the trade name of PastoCovac Plus in Iran, is based on a protein subunit platform in Cuba and completed preclinical and toxicological assessments. This study aimed at presenting the steps of vaccine technology transfer from Cuba to Iran. This study provides the first practical comparability results in Iran to ensure the quality, safety and efficacy of a protein subunit vaccine against COVID-19 after a successful technology transfer from Cuba. PastoCovac Plus was transferred to Iran at the formulation stage. The assessment of the active ingredient pharmaceutical (API) was achieved through physicochemical and clinical data collection and tests to assure if there was any adverse impact on the vaccination results. In order to assess the quality of the vaccine product after technology transfer, we sought different properties including regulatory features, physicochemical quality, vaccine potency and stability as well as its immunogenicity and safety. Following the evaluation of the clinical quality attributes (CQAs) based on the standard protocols, the results showed that the two vaccines are highly similar and comparable, with no considerable effect on safety or efficacy profiles. The CQAs were all in the acceptance limits in terms of safety and efficacy as well as clinical evaluation results. The immunogenicity evaluation also confirmed no significant differences between the vaccines regarding reinfection (P = 0.199) or vaccine breakthrough (P = 0.176). Furthermore, the level of anti-spike and neutralizing antibodies in the both vaccine groups was not significantly different indicating the equality of performance between the two vaccines. According to the results of the quality and clinical assessment of this study, we achieved an acceptable quality attributes and acceptant limits in terms of safety and efficacy of the vaccines pre and post technology transfer., (© 2024. The Author(s).)

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.)

Considering menstruation as a crucial factor in females' health and fertility, any factor that could change its cycle is important. This study was conducted from April 2021 to October 2022 on females who got 3 doses of vaccines against SARS-CoV-2 through different platforms. The participants were requested to provide the trained experts with any changes regarding menstrual cycles after each dose of the vaccine up to 6 months after the booster shots. The disturbances related to the vaccines were identified by the adverse events committee to find possible associations with the applied vaccines. Of 308 women who participated until the end of the study, 22 (7.1%) complained about at least one abnormality in their menstrual patterns. The most common disturbance was metrorrhagia as 10 (48%) incidences followed by menorrhagia as 6 events (24.2%). Notably, the identified complaints were persistent in 59% of the patients. In addition, 14 studied cases developed COVID-19 infection after menstrual disorders. In these cases, COVID-19 could also play a role in the persistence of postvaccine menstrual disturbances. COVID-19 vaccination could affect menstrual cycle in women with no remarkable previous medical history. More longitudinal studies are required regarding this issue., Competing Interests: The authors declare that they have no relevant financial or nonfinancial conflicts of interest., (Copyright © 2024 Mona Sadat Larijani et al.)

Purpose: Paraprobiotics are a non-viable form of probiotics that are reported to provide significant health benefits. Nevertheless, little is known about the beneficial effects of paraprobiotics on inflammatory bowel disease. Although probiotics show potential as therapeutic agents for a range of diseases, including inflammatory bowel disease (IBD), there are certain risks associated with their use. These risks include toxin production, hemolytic potential, antibiotic resistance, and the need to analyze metabolic activities. Hence Using paraprobiotic with the lower aforementioned risk would therefore be the preferable option. Here, we conducted an in vivo study to evaluate the preventive effect of our native paraprobiotic cocktail against dextran sulfate sodium (DSS)-induced murine colitis by affecting the autophagy signaling pathway., Methods: Four-week-old male C57Bl/6 mice were randomly divided into three groups after a two-week acclimation period with normal standard laboratory food diet. Mice were administered PBS (PBS group as control), PBS along with DSS (DSS group, as a control), and a cocktail of paraprobiotics along with DSS (Para group). The severity of colitis, length and histopathology of the colon were evaluated. In addition, the expression of autophagy was assessed using real-time PCR., Results: The results showed that administration of the paraprobiotic cocktail to DSS-treated mice inhibited the severity of colitis symptoms, as evidenced by the inhibition of weight loss and DAI, as well as histopathological scores in the study colon, as well as shortening of colon length caused by DSS. In contrast to the DSS group, the cocktail was able to modulate inflammation through upregulation of autophagy-related genes (becline 1, atg5, atg7, atg12, and atg13)., Conclusion: Although there are some limitations in our investigation, such as the dosage and duration of treatments, our native paraprobiotic blend effectively prevented the advancement of colitis. This suggests that it plays a vital role in regulating inflammation and preventing colitis by promoting the autophagy mechanism in cases where the consumption of probiotics may have negative consequences., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

PastoCovac is a subunit protein vaccine against COVID-19 which contains the tetanus toxoid as a carrier conjugated to SARS-CoV-2 RBD. The primary goal of the tetanus application was to elicit a stronger specific response in the individuals. However, conjugate vaccines have the potency to generate anticarrier antibodies in addition to the target antigen. Therefore, the present study aimed to evaluate the PastoCovac vaccine in the humoral immune induction against tetanus. Six groups of individuals, including those who received one, two, or three doses of the PastoCovac vaccine, Td vaccine, and also the controls who received other COVID-19 vaccines (except PastoCovac), were investigated. The anti-tetanus IgG was assessed by an ELISA assay in all vaccinated groups. The antibody persistency against tetanus in the group who received one dose of the PastoCovac vaccine was also assessed on day 60, 90, and 180 after the last injection. The anti-tetanus antibody titer in the three groups of PastoCovac recipients was positive, though additional doses of the vaccine led to a significant antibody rise ( p = 0.003). Notably, the comparison of the mean antibody titer between the Td recipients and those who received one/two doses of PastoCovac showed that the mean rise in the antibody titer before and after the injection was not significant. Although the antibody titer on day 180 decreased to a lower level than on day 21, it was still estimated to be highly positive against tetanus. Eventually, none of the PastoCovac recipients presented vaccine side-effects during the follow-up. The current data indicate that the tetanus conjugate vaccine against COVID-19, PastoCovac, could induce immune responses against tetanus, which can persist for at least 6 months. Combination vaccine formulae containing TT and DT as carriers for conjugate vaccines could be considered instead of TT and/or DT boosters in adults if they are indicated.

This study evaluated the possible effects of blood types on coronavirus disease (COVID-19) vaccine immunogenicity and antibody (Ab) persistency. Five different vaccinated groups against COVID-19 were investigated at Pasteur Institute of Iran from April 2021 to December 2022. Anti-Spike IgG and neutralizing Ab rise were tracked on Day 21 as well as the humoral immune persistency assessment 180 after booster shots. Late adverse events up to 6 months after the booster dose were collected. The results showed that blood type A, led to a significantly higher anti-Spike Ab rise in AstraZeneca primed recipients in comparison with Sinopharm primed ones in heterologous regimens (p: 0.019). Furthermore, blood type O was a great co-effector in homologous AstraZeneca recipients regarding neutralizing Ab rise (0.013). In addition, blood type O led to a better anti-Spike Ab persistency in the Sinopharm homologous group whereas type A had the best effect on neutralizing Ab durability in the same vaccine group. What is more, Rh-positive individuals in AstraZeneca + PastoCovac Plus group had a higher rate of anti-Spike Ab rise (p = 0.001). Neutralizing Ab rise was also induced in AstraZeneca homologous and heterologous regimens of Rh-positive individuals significantly higher than Sinopharm primed cases. The present study showed the potential impact of blood types A/O and Rh-positive on a better humoral immune responses and Ab persistency. It is proposed that blood type A and Rh-positive could increase the Ab rise in AstraZeneca vaccinated individuals. Moreover, blood type O might be a better co-effector of anti-Spike Ab persistency in Sinopharm recipients., (© 2024 Wiley Periodicals LLC.)

In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications., 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.

Several studies have shown that probiotics can prevent and reduce inflammation in inflammation-related diseases. However, few studies have focused on the interaction between host and probiotics in modulating the immune system through autophagy. Therefore, we aimed to investigate the preventive and/or therapeutic effects of native potential probiotic breast milk-isolated Bifidobacterium spp. (i.e. B. bifidum, B. longum, and B. infantis) on the inflammatory cascade by affecting autophagy gene expression 24 and 48 h after treatment. Autophagy genes involved in different stages of the autophagy process were selected by quantitative polymerase chain reaction (qPCR). Gene expression investigation was accomplished by exposing the human colorectal adenocarcinoma cell line (HT-29) to sonicated pathogens (1.5 × 108 bacterial CFU ml-1) and adding Bifidobacterium spp. (MOI10) before, after, and simultaneously with induction of inflammation. An equal volume of RPMI medium was used as a control. Generally, our native potential probiotic Bifidobacterium spp. can increase the autophagy gene expression in comparison with pathogen. Moreover, an increase in gene expression was observed with our probiotic strains' consumption in all stages of autophagy. Totally, our selected Bifidobacterium spp. can increase autophagy gene expression before, simultaneously, and after the inflammation induction, so they can prevent and reduce inflammation in an in vitro model of inflammation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies.The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14 th Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines.The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2-120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history.Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ' medical history and also through consulting with healthcare providers before vaccination., (© 2023. The Author(s).)

Background: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV., Materials and Methods: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses., Results: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group., Conclusions: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Eybpoosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.)

COVID-19 pandemic has been managed through global vaccination programs. However, the antibody waning in various types of vaccines came to notice. Hereby, PastoCovac Plus as a protein subunit vaccine was investigated in immunized health care workers by COVAXIN (BBV152). The booster vaccine was recommended at least three months post the second dose of COVAXIN. Sera collection was done before and after each injection. SARS-CoV-2 PCR test was done monthly to detect any asymptomatic and symptomatic vaccine breakthrough. 47.9 and 24.3% of the participants were seronegative for anti-N and anti-S antibodies three months after the second dose of COVAXIN, respectively. On average, fold-rises of 70, 93, 8 and mean-rises of 23.32, 892.4, 5.59 were recorded regarding neutralizing antibody, quantitative and semi-quantitative anti-Spike antibody, respectively. Anti-Spike and neutralizing antibodies seroconversion was seen 59.3% and 45.7%, respectively. The vaccine breakthrough assessment showed that all the isolated samples belonged to SARS-CoV-2 Delta variant. PastoCovac Plus boosting is strongly recommended in combination with inactivated vaccine platforms against SARS-CoV-2., 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., (© 2023 Published by Elsevier Ltd.)

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate three different boosters' immunogenicity and safety in individuals with at least one underlying disease (UD) (obesity, hypertension, and diabetes mellitus) with healthy ones (HC) who were primed with two doses of the BBIBP-CorV vaccine and received a booster shot of the same priming vaccine or protein subunit vaccines, PastoCovac Plus or PastoCovac. One hundred and forty subjects including sixty-three ones with a comorbidity and seventy-seven healthy ones were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 postbooster shot for evaluating safety outcomes. Significantly increased titers of antispike, antiRBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose. Nevertheless, the titer of antispike IgG and anti-RBD IgG was lower in the UD group compared to the HC group. The long-term assessment regarding persistence of humoral immune responses showed that the induced antibodies were detectable up to 180 days postbooster shots though with a declined titer in both groups with no significant differences ( p > 0.05). Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension subgroup. PastoCovac Plus and PastoCovac boosters induced a higher fold rise in antibodies in UD individuals than BBIBP-CorV booster recipients. No serious AEs after the booster injection were recorded. The overall incidence of AEs after the booster injection was higher in the UD group than the HC group among whom the highest systemic rate of AEs was seen in the BBIBP-CorV booster recipients. In conclusion, administration of COVID-19 boosters could similarly induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with two doses of the BBIBP-CorV. Protein-based boosters with higher a higher fold rise in antibodies and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile., (© 2023. The Author(s).)

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has been a leading cause of death in the world in the last few years. This study has investigated various causes and risk factors that may lead to death due to this disease., Methods: From June to October 2020, 98 expired and 196 recovered patients were studied for risk factors, underlying diseases, and laboratory findings that could lead to disease progression and mortality., Results: There was a significant relationship in terms of blood pressure, age, oxygen saturation, tachycardia, tachypnea, the interval between the onset of symptoms and hospitalization, diabetes mellitus, lung disease, cardiovascular disease, history of opium abuse, C-reactive protein, white blood cell, lymphocytes, hemoglobin, creatinine elevation, elevated liver enzyme, creatine phosphokinase, lactate dehydrogenase, ferritin, D-dimer, troponin, prothrombin time, international normalized ratio, intensive care unit admission days, arrhythmia, sepsis, acute respiratory distress syndrome, acute kidney injury (AKI), and the type of antiviral and antibiotic therapy between the two groups of patients., Conclusions: Mortality due to COVID-19 is affected by various causes such as age, underlying diseases, and complications that may occur in the course of the disease (e.g., arrhythmia, myocardial infarction, and AKI). By accurately identifying these causes and risk factors, we can prevent these complications and the mortality from COVID-19., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2022 Hossein Mazaherpour et al.)

The prevalence and variety complaints of COVID-19 cases in a long term have been investigated in recent studies. The symptoms over the time are various and unpredictable which may persist several weeks after full recovery. The importance of long-COVID-19 manifestations includes its effect on the recovered cases which requires a rational management based on an accurate guideline to handle post-acute COVID-19 state. The aim of this study was to evaluate the incidence of post-acute COVID-19 syndrome and to identify the associated risk factors as well as to compare new and persistent symptoms at different post-acute phases. Totally 254 individuals from Pasteur Institute of Iran (or/and their relatives) were investigated who had a previously confirmed COVID-19 PCR test. The long-term manifestations of the virus were categorized through a time window as acute, ongoing, post-COVID and persistent phases and the individuals were assessed by the face-to-face or the phone call interview according to their complaints. The data were then statistically analyzed to determine the frequency of the symptoms and also the associated factors in which a p value < 0.05 was considered significant. Except a small asymptotic group of five, 249 cases progressed the symptoms to acute phase among which 64.1% reported at least one symptom in post-acute phase. Neurological sequelae were found as the most frequent symptom (91.6%). Furthermore, there was a significant association between the underlying diseases, age and acute phase symptoms to the post-acute phase syndrome susceptibility (p < 0.05). In conclusion, the increasing number of the reports and studies on long COVID-19 which can hugely affect the life quality should be more investigated and explored in terms of the pathophysiology to achieve appropriate treatments in time. The clusters of symptoms, specially a combination of neurological signs, presenting over months after the recovery impose a huge difficulty to the recovered population., (Copyright © 2022. Published by Elsevier Ltd.)

Inflammation plays a critical role in the promotion of hepatocyte damage and liver fibrosis. In recent years the protective role of Akkermansia muciniphila, a next-generation beneficial microbe, has been suggested for metabolic and inflammatory disorders. In this study, we aimed to evaluate the effects of live and pasteurized A. muciniphila and its extra cellular vesicles (EVs) on inflammatory markers involved in liver fibrosis in a mouse model of a high-fat diet (HFD)/carbon tetrachloride (CCl 4 )-induced liver injury. Firstly, the responses of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs were examined in the quiescent and LPS-activated LX-2 cells. Next, the anti-inflammatory effects of different forms of A. muciniphila were examined in the mouse model of HFD/CCl 4 -induced liver injury. The gene expression of various inflammatory markers was evaluated in liver, colon, and white adipose tissues. The cytokine secretion in the liver and white adipose tissues was also measured by ELISA. The results showed that administration of live and pasteurized A. muciniphila and its EVs leads to amelioration in HSCs activation. Based on data obtained from the histopathological analysis, an improvement in gut health was observed through enhancing the epithelium and mucosal layer thickness and strengthening the intestinal integrity in all treatments. Moreover, live A. muciniphila and its EVs had inhibitory effects on liver inflammation and hepatocytes damage. In addition, the tissue cytokine production and inflammatory gene expression levels revealed that live A. muciniphila and its EVs had more pronounced anti-inflammatory effects on liver and adipose tissues. Furthermore, EVs had better effects on the modulation of gene expression related to TLRs, PPARs, and immune response in the liver. In conclusion, the present results showed that oral administration of A. muciniphila and its derivatives for four weeks could enhance the intestinal integrity and anti-inflammatory responses of the colon, adipose, and liver tissues and subsequently prevent liver injury in HFD/CCL 4 mice., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) may lead to acute respiratory disease; cardiovascular, gastrointestinal, and coagulation complications; and even death. One of the major complications is cardiovascular disorders, including arrhythmias, myocarditis, pericarditis, and acute coronary artery disease. The aim of this study was to evaluate the frequency of cardiovascular complications and to determine its association with the prognosis of COVID-19 patients. In a prospective analytic study, 137 hospitalized COVID-19 patients were enrolled. During hospitalization, an electrocardiogram (ECG) was performed every other day, and laboratory tests such as cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were done 0, 6, and 12 hours after admission. These tests were repeated for patients with chest pain or ECG changes. Patients were categorized into three groups (improved, complicated, and expired patients) and assessed for the rate and type of arrhythmias, cardiac complications, lab tests, and outcomes of treatments. There was no significant relationship among the three groups related to primary arrhythmia and arrhythmias during treatment. The most common arrhythmia during hospitalization and after treatment was ST-T fragment changes. There was a significant age difference between the three groups ( P = 0.001). There was a significant difference among the three groups for some underlying diseases, including diabetes mellitus ( P = 0.003) and hyperlipidemia ( P = 0.004). In our study, different types of arrhythmias had no association with patients' outcomes but age over 60 years, diabetes mellitus, and hyperlipidemia played an important role in the prognosis of COVID-19 cases., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Hossein Mazaherpour et al.)

Background: Several studies have shown that probiotics have beneficial effects on weight control and metabolic health. In addition to probiotics, recent studies have investigated the effects of paraprobiotics and postbiotics. Therefore, we evaluated the preventive effects of live and pasteurized Akkermansia muciniphila MucT (A. muciniphila) and its extracellular vesicles (EVs) on HFD-induced obesity., Results: The results showed that body weight, metabolic tissues weight, food consumption, and plasma metabolic parameters were increased in the HFD group, whereas A. muciniphila preventive treatments inhibited these HFD. The effects of pasteurized A. muciniphila and its extracellular vesicles were more noticeable than its active form. The HFD led to an increase in the colonic, adipose tissue, and liver inflammations and increased the expression of genes involved in lipid metabolism and homeostasis. Nevertheless, these effects were inhibited in mice that were administered A. muciniphila and its EVs. The assessment of the gut microbiota revealed significant differences in the microbiota composition after feeding with HFD. However, all treatments restored the alterations in some bacterial genera and closely resemble the control group. Also, the correlation analysis indicated that some gut microbiota might be associated with obesity-related indices., Conclusions: Pasteurized A. muciniphila and its EVs, as paraprobiotic and postbiotic agents, were found to play a key role in the regulation of metabolic functions to prevent obesity, probably by affecting the gut-adipose-liver axis., (© 2021. The Author(s).)

The gastrointestinal (GI) tract is an essential reservoir of serotonin or 5-hydroxytryptamine (5-HT), which possesses a set of bacterial species communities. Intestinal microbiota has the ability to modulate the host's serotonin system. In this regard, we evaluated the effect of Akkermansia muciniphila and Faecalibacterium prausnitzii along with their extracellular vesicles (EVs) on serotonin system-related genes in human epithelial colorectal adenocarcinoma (Caco-2) cells. The differentiated Caco-2 cells were treated with A. muciniphila and F. prausnitzii with the multiplicity of infection ratio of 1 and 10 and the EV concentration of 1 μg/mL and 50 μg/mL, respectively. After 24 h, the serotonin level was quantified using an ELISA kit and also the gene expression of serotonin system-related genes was examined using the quantitative real-time PCR method. According to the results, treatment with A. muciniphila and F. prausnitzii-derived EVs increased the serotonin level, while none of the bacteria could affect the serotonin level in the Caco-2 cells. Both bacteria had significant effects on the mRNA expression of serotonin system-related genes in the Caco-2 cells. Moreover, we observed that A. muciniphila and F. prausnitzii-derived EVs could impact the expression of major genes involved in the serotonin system. Our findings showed that A. muciniphila and F. prausnitzii along with their EVs could modulate serotonin system-related genes; hence, they may be useful in microbiota modulation therapies to maintain the homeostasis of the serotonin system., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Akkermansia muciniphila, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease. In this study, we aimed to determine the beneficial effects of live and pasteurized A. muciniphila and its extracellular vesicles (EVs) on the prevention of liver fibrosis. The response of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs was examined in quiescent, lipopolysaccharide (LPS)-activated LX-2 cells. Liver fibrosis was induced in 8-week-old C57BL/6 mice, using a high-fat diet (HFD) and carbon tetrachloride (CCl4) administration for 4 weeks. The mice were concomitantly treated via oral gavage with three forms of bacteria. The relative expression of different fibrosis and inflammatory markers was assessed in the tissues. Histological markers, serum biochemical parameters, and cytokine production were also analyzed, and their correlations with the relative abundance of targeted fecal bacteria were examined. All A. muciniphila preparations exhibited protective effects against HSC activation; however, EVs showed the greatest activity in HSC regression. Oral gavage with A. muciniphila ameliorated the serum biochemical and inflammatory cytokines and improved liver and colon histopathological damages. The relative expression of fibrosis and inflammatory biomarkers was substantially attenuated in the tissues of all treated mice. The composition of targeted stool bacteria in the live A. muciniphila group was clearly different from that in the fibrosis group. This study indicated that A. muciniphila and its derivatives could successfully protect against HFD/CCl4-induced liver injury. However, further studies are needed to prove the beneficial effects of A. muciniphila on the liver. IMPORTANCE Akkermansia muciniphila, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease. In this study, we aimed to determine the beneficial effects of live and pasteurized A. muciniphila and its extracellular vesicles (EVs) on the prevention of liver fibrosis. The results of the present study indicated that oral administration of live and pasteurized A. muciniphila and its EVs could normalize the fecal targeted bacteria composition, improve the intestinal permeability, modulate inflammatory responses, and subsequently prevent liver injury in HFD/CCl4-administered mice. Following the improvement of intestinal and liver histopathology, HFD/CCl4-induced kidney damage and adipose tissue inflammation were also ameliorated by different A. muciniphila treatments.

Recently, Akkermansia muciniphila an anaerobic member of the gut microbiota, has been proposed as a next-generation probiotic. The aim of this study was evaluation of the effect of alive and pasteurized A. muciniphila on health status, intestinal integrity, immune response, lipid metabolism, and gut microbial composition in normal-diet fed mice as well as direct effects of the bacterium on Caco-2 cell line. A total of 30 mice were distributed into three different groups, control, alive, and pasteurized A. muciniphila-treated group. After acclimation, control and treatment groups were administrated with PBS and 10 9  CFU/200µL of bacterial suspension for 5 weeks, respectively. Besides, Caco-2 separately exposed to alive, pasteurized A. muciniphila and PBS for 24 h. The results showed that administration of A. muciniphila leads to reduction in body, liver, and white adipose weight. Histology data revealed both treatments had no adverse effects in colon, liver, and adipose tissues as well as induced better gut structure. Moreover, biochemical parameters and inflammatory biomarkers in plasma demonstrated that pasteurized A. muciniphila had more pronounce effect. Furthermore, alive A. muciniphia had better effects on the modulation of gene expression related to fatty acid synthesis, energy homeostasis, and immune response in the liver; meanwhile, these effects in the adipose was more in the pasteurized A. muciniphila administration. More importantly, the improvement of gut health by enhancing strengthen intestinal integrity and maintaining immune homeostasis was seen in both treatments; notably, pasteurized A. muciniphila had more effective. Similarly, treatment with the pasteurized form more effectively upregulated tight junction and regulated immune response-related genes in Caco-2 cell line. Both treatments triggered the improvement of microbiota communities, particularly the alive form. Therefore, both forms of A. muciniphila could modulate lipid and immune homeostasis, improved some gut microbiota, and promoted the overall health, while all these effects were dominantly observed in pasteurized form. In conclusion, pasteurized A. muciniphila can be considered as new medical supplement to maintain health state and prevent diseases in normal mice through different mechanisms., (© 2021. The Author(s).)

Inflammatory bowel diseases (IBDs) are immune-mediated, chronic relapsing diseases with a rising prevalence worldwide in both adult and pediatric populations. Treatment options for immune-mediated diseases, including IBDs, are traditional steroids, immunomodulators, and biologics, none of which are capable of inducing long-lasting remission in all patients. Dendritic cells (DCs) play a fundamental role in inducing tolerance and regulating T cells and their tolerogenic functions. Hence, modulation of intestinal mucosal immunity by DCs could provide a novel, additional tool for the treatment of IBD. Recent evidence indicates that probiotic bacteria might impact immunomodulation both in vitro and in vivo by regulating DCs' maturation and producing tolerogenic DCs (tolDCs) which, in turn, might dampen inflammation. In this review, we will discuss this evidence and the mechanisms of action of probiotics and their metabolites in inducing tolDCs in IBDs and some conditions associated with them.

Objectives: Osteoporosis is characterized by slow deterioration in bone mass and disruption of its structure, leading to an increased risk of bone fractures. Gut microbiota plays an important role in the transport and absorption of nutrients needed for bone health. Akkermansia muciniphila is one of the gut microbiota members that its beneficial role in prevention of metabolic disorder was suggested. The aim of the current pilot study was the assessment of fecal A. muciniphila in patients with osteoporosis and osteopenia., Methods: A total of 36 subjects including eight with osteoporosis (three men and five women), eight with osteopenia (two men and six women), and 20 normal controls (six men and 14 women) were selected. Microbial genome was extracted from fresh stool samples. The bacterial load was determined by quantitative real-time PCR using 16S rRNA specific primers., Results: The participants' mean age in the osteoporosis, osteopenia and control groups were 61.71, 45 and 45.05 years, respectively. The majority of osteoporosis patients were post-menopause women, while in osteopenia group was pre-menopause. There were significant differences in terms of age, T-score, Z-score, and menopause among groups ( P value  < 0.05). The presence of A. muciniphila was higher in the healthy group compared to osteopenia group; however, these differences were not statistically significant., Conclusions: In conclusion, however, there was no statistically significant difference between the study groups; it seems that the load of A. muciniphila may be related to bone health. Further in vivo and in vitro studies are needed to investigate the immunological and biochemical pathways., Competing Interests: Conflict of interestNo relevant conflict of interest has been declared by the authors., (© Springer Nature Switzerland AG 2021.)

Several studies have reported that the host-microbe interactions in the gut modulate the host serotonin or 5-hydroxytryptamine (5-HT) system. Here, we evaluated the effects of Akkermansia muciniphila and its extracellular vesicles (EVs) on genes pertaining to the serotonergic system in the colon and hippocampus of mice. Male C57BL/6J mice were administered viable A. muciniphila and its EVs for 4 weeks. The serotonin levels in the colon, hippocampus, and serum of mice, as well as the human colon carcinoma cells (Caco-2), were measured by ELISA assays. Also, the effects of A. muciniphila and its EVs on the expression of serotonin system genes in the colon and hippocampus were examined. A. muciniphila and its EVs may have a biological effect on the induction of serotonin levels in the colon and hippocampus of mice. Also, EVs increased the serotonin level in the Caco-2 cell line. In contrast, both treatments decreased the serotonin level in the serum. Both the bacterium and its EVs had significant effects on the mRNA expression of genes, involved in serotonin signaling/metabolism in the colon and hippocampus of mice. Moreover, A. muciniphila and its EVs affected the mRNA expression of inflammatory cytokines (Il-10 and Tnf-α) in the colon, however, there is no significant difference in inflammatory cell infiltrate in the histopathology of the colon. The presence of A. muciniphila and its EVs in the gut promotes serotonin concentration, they also affect serotonin signaling/metabolism through the gut-brain axis and may be considered in new therapeutic strategies to ameliorate serotonin-related disorders.

Background: Akkermansia muciniphila is an anaerobic bacterium residing in the healthy intestinal tract of host and its quantity has a negative correlation with various host diseases. This study for the first time provides a holistic bibliometric aspect of Akkermansi muciniphila research in the literature and shows the hot topic terms of these articles in any period of time., Methods: Scopus database was selected to retrieve documents relevant to Akkermansia muciniphila in any language up to 2019. The bibliometric profile of Akkermansia muciniphila articles including subject area, year distribution, citations, institutions, journals, authors, and countries was systematically characterized and the collaboration networks of authors and countries as well as the burst detection algorithm of the words in the titles, abstracts and keywords were visualized., Results: There is a progressive growing trend in research on Akkermansia from 2004 to 2019 with a total of 566 articles during this period. Out of 353 original articles, there are 194 animal studies (155 studies on mice) and 112 human studies. Also, 65 various diseases were investigated in these studies. The most focused conditions are obesity (71 articles) and type2 diabetes (39 articles). The United States is the leading country on Akkermansia publications (n = 132), followed by China (n = 95). Frontiers in Microbiology is the most dominant journal with 23 Akkermansia publications. In addition, "cancer" is the hot topic of recent Akkermansia research., Conclusion: Akkermansia research is of progressive interest during the last decade and the studies on this subject move towards its relationship with cancer and its promising effect on health.

The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. Microbiota disruption affects the immune function, metabolism, and causes several diseases. Therefore, understanding how the microbiome is adjusted, and identifying methods for manipulating it is critical. Studies have found that there is an inverse association between MicroRNAs (miRNAs) abundance and microbe abundance. miRNAs are known to be engaged in post-transcription regulation of cell-autonomous gene expression. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. Here, we review recent studies on the role of miRNAs as a component of outer membrane vesicles (OMVs) in the composition of gut microbiota and their significance in the human situation of health and diseases and discuss their effect on inflammatory responses and dysbiosis. Further, we explain how probiotics exert influence on the expression of miRNAs., Competing Interests: Declaration of competing interest The authors declare that they have no Conflict interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Recent evidence suggests that probiotics can restore the mucosal barrier integrity, ameliorate inflammation, and promote homeostasis required for metabolism in obesity by affecting the gut microbiota composition. In this study, we investigated the effect of Akkermansia muciniphila and its extracellular vesicles (EVs) on obesity-related genes in microarray datasets and evaluated the cell line and C57BL/6 mice by conducting RT-PCR and ELISA assays. A. muciniphila -derived EVs caused a more significant loss in body and fat weight of high-fat diet (HFD)-fed mice, compared with the bacterium itself. Moreover, treatment with A. muciniphila and EVs had significant effects on lipid metabolism and expression of inflammatory markers in adipose tissues. Both treatments improved the intestinal barrier integrity, inflammation, energy balance, and blood parameters (i.e., lipid profile and glucose level). Our findings showed that A. muciniphila -derived EVs contain various biomolecules, which can have a positive impact on obesity by affecting the involved genes. Also, our results showed that A. muciniphila and its EVs had a significant relationship with intestinal homeostasis, which highlights their positive role in obesity treatment. In conclusion, A. muciniphila -derived EVs can be used as new therapeutic strategies to ameliorate HFD-induced obesity by affecting various mechanisms., (Copyright © 2019 Ashrafian, Shahriary, Behrouzi, Moradi, Keshavarz Azizi Raftar, Lari, Hadifar, Yaghoubfar, Ahmadi Badi, Khatami, Vaziri and Siadat.)

Overweight and obesity are among the most prevalent non-communicable diseases which are generally treated successfully by bariatric or sleeve surgery. There are evidences affirming that sleeve surgery can manipulate the pH of the stomach and interact with the metabolism of fatty acids, carbohydrates, and bile acid transfer, leading to the overgrowth of gut microbiota. Therefore, this study aims to review the changes in gut microbiota and hormones after bariatric surgery.

Aim: We assessed effect of Akkermansia muciniphila and its extracellular vesicles on toll-like receptors and tight junction expression in human epithelial colorectal adenocarcinoma cells (Caco-2)., Background: The intestinal microbiota plays an important role in the intestinal homeostasis through its metabolites and derivatives. Interacting with immune cells and intestinal epithelial pattern recognition receptors (PRRs), intestinal microbiota regulates the function of the digestive barrier and inflammation caused by the metabolic diseases., Methods: A. muciniphila was cultured on a mucin-containing medium and its EVs was extracted by ultracentrifugation. This bacterium was treated in the MOI=10 and its EVs at the concentrations of 0.1, 0.5 and 5 µg on Caco-2 cells. After 24 hours, the expression of tight junction and toll-like receptor genes were investigated by quantitative real time PCR method., Results: A. muciniphila increased the expression of tlr2 and tlr4 . However, EVs at all of the concentrations showed a decrease in tlr4 expression. EVs at the concentrations of 0.1 and 0.5 µg/ml decreased the expression of tlr2 . A. muciniphila significantly increased the expression of ocldn and cldn4 . Both this bacterium and EVs increased the expression of zo2 in the cell line. Furthermore, this data show that A. muciniphila derived EVs have a dose-independent effect on Caco-2 cells., Conclusion: This preliminary research shows A. muciniphila and its EVs both may increase the integrity of the intestinal barrier. A. muciniphila derived EVs also reduces the inflammation so that EVs of this bacterium can be used as an appropriate target for the treatment of metabolic syndrome and inflammatory bowel diseases., Competing Interests: The authors declare that they have no conflict of interest.

The authors report an adult individual found to have very unusual origins of additional left and right pericallosal arteries that are normally only branches of the anterior cerebral artery. These vessels both arose from the vertebrobasilar system. The right accessory pericallosal artery was found to originate from the ipsilateral posterior inferior cerebellar artery and the left accessory pericallosal artery was found to originate from the ipsilateral posterior cerebral artery. To our knowledge, this variation has not been previously reported. The embryological and surgical implications of this finding are discussed.