Search

Masoumeh Azimirad,1,* YoungJae Jo,2,* Min-Sueng Kim,2 Minsoo Jeong,2 Shabnam Shahrokh,3 Hamid Asadzadeh Aghdaei,4 Mohammad Reza Zali,3 Seungjun Lee,5 Abbas Yadegar,1 Jae-Ho Shin2 1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea; 3Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Food Science and Nutrition, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea*These authors contributed equally to this workCorrespondence: Abbas Yadegar; Jae-Ho Shin Tel +98-21-22432518; +82 53-950-5716Fax +98-21-22432527; +82 53-953-7233Email babak_y1983@yahoo.com; jhshin@knu.ac.krBackground and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.Keywords: fecal microbiota transplantation, Clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis

Masoumeh Azimirad,1 Abbas Yadegar,1 Fatemeh Gholami,1 Shabnam Shahrokh,2 Hamid Asadzadeh Aghdaei,3 Gianluca Ianiro,4 Hidekazu Suzuki,5 Giovanni Cammarota,4 Mohammad Reza Zali2 1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 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, Iran; 4Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of Sacred Heart, Rome, Italy; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, JapanCorrespondence: Abbas YadegarFoodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St., Velenjak, Tehran, IranEmail a.yadegar@sbmu.ac.irPurpose: Fecal microbiota transplantation (FMT) is an effective treatment option for patients with recurrent Clostridioides difficile infection (rCDI). However, there is a paucity of evidence regarding its efficacy and safety in patients with rCDI and concurrent inflammatory bowel disease (IBD). Here, we present a single-center experience of FMT for treatment of rCDI in Iranian patients with IBD.Patients and Methods: Eight patients with established IBD (7 with ulcerative colitis and 1 with Crohn’s disease) who underwent at least one FMT via colonoscopy for treatment of rCDI were enrolled in this study. Demographics, pre-FMT and post-FMT IBD activity, efficacy for rCDI and adverse events (AEs) were assessed during a 6-month follow-up period. All patients had experienced 3 episodes of rCDI and were refractory to conventional therapies with metronidazole and vancomycin. Primary cure and secondary cure rates were assessed after FMT treatments.Results: A total of 10 FMTs were performed via colonoscopy in 8 patients (6/8; 75% men) with a median age of 35 years (range: 22– 60). Two patients received a second FMT. Overall, the primary and secondary cure rates were 75% and 100%, respectively. Two patients developed CPE-producing C. perfringens diagnoses after second FMTs. There were no other AEs, and no patient experienced IBD flare.Conclusion: We demonstrated that FMT appears to be an effective, safe and rational therapeutic alternative for resolution of rCDI in patients with underlying IBD. Furthermore, we suggest implementing the CPE-producing C. perfringens testing in the screening of FMT donors.Keywords: fecal microbiota transplantation, recurrent Clostridioides difficile infection, inflammatory bowel disease, FMT, rCDI, IBD, Iran

Saeed Moayedi,1 Abbas Yadegar,2 Saeed Balalaie,3 Mahdiyeh Yarmohammadi,2 Mohammad Reza Zali,4 Hidekazu Suzuki,5 Gert Fricker,6 Ismaeil Haririan1 1Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran, Iran; 4Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan; 6Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Heidelberg, GermanyCorrespondence: Ismaeil HaririanDepartment of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranEmail haririan@tums.ac.irIntroduction: Currently, gastroesophageal reflux disease (GERD) is one of the most ubiquitous problems in clinical practice. An antacid-alginate combination (under the trade name Gaviscon) is a natural-based product that effectively suppresses GERD. This product acts via the formation of viscous gel that floats on the top of the gastric content. On the other hand, efficient management of Helicobacter pylori infection with minimal side effects is an important goal for gastroenterologists. Furthermore, some H. pylori-positive patients suffer from GERD.Methods: Here, we present the results of investigations on alginate conjugated to sugar codes in order to find initial clues regarding the potential ability of this conjugate in the simultaneous prophylaxis of GERD and H. pylori infection in an in vitro assay.Results: It is noteworthy that our results reveal that sugar codes conjugated alginate considerably decrease (approximately 74%) the adhesion of H. pylori to gastric epithelial cells in vitro. Moreover, surprisingly after conjugation of sugar codes, alginate can maintain its ability to create gel. Our results demonstrate that alginate conjugated to sugar codes is not cytotoxic.Conclusion: The preparation of these conjugates can be regarded as the first step to establish a new roadmap for the simultaneous prevention of GERD and H. pylori infection in future studies on in vivo models.Keywords: GERD, Helicobacter pylori infection, sugar codes, alginate, conjugation

Abstract Introduction This study aimed to identify the factors most strongly associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk score in patients with type 2 diabetes (T2D). Methods This cross-sectional study included 4698 patients with T2D over an 11-year period (2010–2021). Patients were categorized into four groups based on their 10-year ASCVD risk score ( 20%). Multinominal regression analysis was used to evaluate the association between various modifiable and non-modifiable risk factors and the ASCVD risk score. Results Of the patients, 35.9% had a 10-year ASCVD risk score below 5%, 12.6% had a score between 5% and 7.5%, 30.8% had a score between 7.5% and 20%, and 19.7% had a score above 20%. Higher ASCVD risk scores were significantly associated with elevated waist-to-hip ratio (WHR > 0.93), pulse pressure, uric acid, triglycerides, and decreased glomerular filtration rate (all p-values 5% to those with scores

This case report explores the left atrial mitral valve cord, an extremely rare congenital anomaly. Typically involving mitral valve leaflets and associated with mild mitral regurgitation, it is rarely documented independently. A 51-year-old patient presented with dizziness, and diagnostic challenges arose during transthoracic echocardiography (TTE). Advanced 3-dimensional transesophageal echocardiography (3D TEE) proved invaluable for accurate mapping, revealing a unique, unattached left atrial mitral valve cord.

Abstract Background Diabetes is a global health problem, and its incidence and complications increase with the duration of the disease and over time. This increase in complications in older patients can lead to disability and a lower quality of life. This study aimed to investigate the rate of diabetes control and complications in older adults. Method This was a cross-section of an ongoing cohort of patients with type 2 diabetes mellitus (T2DM) aged 65 years and older. The clinical and laboratory characteristics of older adult patients with T2DM in good and intermediate health conditions were collected between 2010 and 2022. Results A total of 2,770 older adult patients with T2DM were enrolled, including 1,530(55.3%) female and 1,240 (44.7%) male participants. Metabolic syndrome, hypertension, and coronary artery disease were the most common comorbidities, affecting 1,889 (71.4%), 1,495 (54.4%), and 786 (29.2%) patients, respectively. Albuminuria was present in 626 (22.6%) patients, while retinopathy was detected in 408 (14.7%) patients, including 6% with proliferative retinopathy. Most patients were treated with oral antidiabetic agents (88.9%), with metformin being the most prescribed medication (85.6%). Statins were prescribed to 71.8% of the patients. The most prescribed antihypertensive medications were angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, prescribed to 54% and 15% of patients, respectively. The hemoglobin A1c (HbA1c) goal (HbA1c

Abstract Background Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal system. So far, no treatment has been identified that can completely cure IBD. Lactobacillus brevis is hypothesized to be beneficial in preventing inflammation. This study aimed to evaluate the potential probiotic effects of live and pasteurized L. brevis IBRC-M10790 on the in vitro cell co-culture model of IBD. Methods An in vitro intestinal model was established using a transwell co-culture system of Caco-2 intestinal epithelial cells and RAW264.7 macrophages. Inflammatory conditions were induced in RAW264.7 cells using lipopolysaccharide. The effects of live and pasteurized L. brevis IBRC-M10790 on inflammatory mediators and epithelial barrier markers were investigated. Results L. brevis IBRC-M10790 was able to significantly decrease the proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and increase the anti-inflammatory cytokine (IL-10) in the in vitro co-culture system. In addition, L. brevis increased adherens and tight junction (TJ) markers (ZO-1, E-cadherin, and Occludin) in Caco-2 intestinal epithelial cells. Based on the results, pasteurized L. brevis showed a higher protective effect than live L. brevis. Conclusions Our findings suggest that live and pasteurized forms of L. brevis possess probiotic properties and can mitigate inflammatory conditions in IBD.

Background: Probiotic administration can be an effective treatment against intestinal inflammation. This study aimed to assess the potential effects of spores isolated from probiotic strains Bacillus subtilis natto and Bacillus coagulans Hammer on inflammation induced by lipopolysaccharide (LPS) in human colon epithelial cells in vitro. Materials and Methods: The viability of HT-29 cells treated with spores derived from B. subtilis natto and B. coagulans Hammer (MOI 10, 100, 1000), as well as LPS (10 µg/ml) was assessed. The anti-inflammatory effects of spores were examined on HT-29 cells that were pre-stimulated with LPS. The expression level of IL-6 and TLR4 genes in HT-29 cells was quantified after 24 h using RT-qPCR. Results: There was no significant reduction in the viability of HT-29 cells after exposure to LPS and various MOIs of probiotic spores. Stimulation of HT-29 cells with LPS significantly increased the expression level of IL-6 and TLR4 in comparison to control (P < 0.0001). Spores isolated from both probiotic strains, B. subtilis natto and B. coagulans Hammer, caused a significant reduction in the gene expression of IL-6 and TLR4 in HT-29 cells compared to LPS control (P < 0.0001). Conclusion: The findings of this study suggest that probiotics-derived spores may exert anti-inflammatory effects through interference with the LPS signaling pathway in colon cancer HT-29 cell line.

Abstract Background So far, high-density lipoprotein cholesterol (HDL-C) levels and mortality were shown to have a U-shaped relationship. Additionally, high HDL-C levels increase the risk of developing a variety of diseases. However, a paucity of data exists regarding the characteristics of people with high HDL-C levels. The aim of this study was to assess the demographics and characteristics of patients with high HDL-C levels and compare their features with normal and low HDL-C groups. Methods As a cross-sectional, matched case–control study, a total of 510 patients with type 2 diabetes (T2D) were enrolled in the study and categorized into three matched groups according to their HDL-C concentrations. The studied groups were matched by their age and gender. Restricted cubic spline (RCS) curves were designed to evaluate the relationship between height, blood pressure, triglyceride, and vitamin D concentrations with the probability of having high HDL-C levels. Furthermore, violin plots were conducted to illustrate the distribution of continuous variables within each group. Results This study showed that having high HDL-C (more than 70 mg/dL) compared to having low HDL-C (less than 40 mg/dL in men and 50 mg/dL in women) was significantly associated with height (OR 0.918, 95% CI 0.866–0.974), systolic blood pressure (SBP) (0.941, 0.910–0.972), vitamin D (0.970, 0.941–0.999), and triglyceride (0.992, 0.987–0.998) serum concentrations. Further analysis investigated that having high HDL-C levels compared to desired HDL-C levels (40 ≤ HDL-C levels

ABSTRACT Background The pediatric community is considered a suitable target for controlling the spread and mortality of viral diseases. In late December 2019, a respiratory disease due to the novel coronavirus, later COVID‐19, hit the globe. The COVID‐19 global disruption had direct and indirect impacts on different aspects of child health. Therefore, surveillance, preventive approaches, and treatment plans for children came into the spotlight. Objective This study aims to discuss the clinical pictures as well as laboratory and radiological findings of the infected children during the COVID‐19 pandemic. The focus of this study is to express the clinical manifestations of respiratory disease in pediatric SARS‐CoV‐2, available therapeutic options, vaccine recommendations, and long COVID sequelae in affected children. This review could serve as a hint for upcoming challenges in pediatric care during future pandemics. Results The clinical presentation of COVID‐19 in pediatrics can range from mild pulmonary disease to acute respiratory distress syndrome (ARDS). Supportive care is a crucial component of the management of pediatric COVID‐19. However, the importance of specializing in how to treat patients with more severe conditions cannot be overstated. Additionally, clinicians must consider prevention strategies as well as potential complications. Conclusion Although the infected patients are dipping day by day, there is a lack of clinical guidelines for pediatric SARS‐CoV‐2‐associated pulmonary diseases. Understanding of the physicians about all aspects of pediatric care during the COVID‐19 pandemic could lead to enhanced quality of future patient care and safety, reduced costs of health policies, and surveil the risk that patients with respiratory viruses can expose to society.

ABSTRACT Background This study aimed to evaluate the relationships of conventional and calculated lipid indices with obesity or overweight in patients with type 2 diabetes (T2D). Methods In this cross‐sectional study, all participants were categorised into three groups: normal weight (18 ≤ BMI

Abstract Background and Aims Literature suggests that oxidative stress plays a crucial role in the progression of diabetes. Since poor glycemic control enhances the formation of advanced glycation end‐products (AGEs) and advanced oxidation protein products (AOPP) in individuals with diabetes, exploring the association between glycation and oxidative states in diabetes could also shed light on potential consequences. This study evaluated the effects of albuminuria on AGEs and AOPP levels and measured their relationship in participants with type 2 diabetes (T2D) with or without albuminuria. Methods A cross‐sectional, matched case‐control study was designed, including 38 T2D subjects with albuminuria and 38 matched T2D subjects with normoalbuminuria. Patients were matched by their body mass index (BMI), age, and duration of diabetes. The unadjusted and adjusted correlation between AGEs and AOPP in the studied groups were analyzed by multiple logistic regression. Using ggplot2, the ties between these two biochemical factors in cases and controls were plotted. Results This study elucidated a significant association between AGEs and AOPP in participants with normoalbuminuria (r = 0.331, p‐value

Abstract Introduction This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease (CAD) in patients with type 2 diabetes (T2D). Methods This was a matched case-control study of 482 patients with T2D in two groups of CAD and (n = 241) non-CAD (n = 241). The patients were classified into four quartiles according to the ApoA1/HDL-C ratio, and multivariate logistic regression analysis was performed to assess the relationship between ApoA1/HDL-C and CAD. ROC analysis was also conducted. Results This study showed that the ApoA1/HDL-C ratio has an independent association with CAD in individuals with T2D. The CAD group exhibited a significantly higher ApoA1/HDL-C ratio than those without CAD (p-value = 0.004). Moreover, the risk of CAD increased significantly across the ApoA1/HDL-C ratio quartiles, with the highest odds in the fourth quartile. The second quartile showed an odds ratio (OR) of 2.03 (p-value = 0.048) compared to the first. Moving to the third quartile, the OR increased to 2.23 (p-value = 0.023). The highest OR was noted in the fourth, reaching 3.41 (p-value = 0.001). Employing a cut-off value of 2.66 and an area under the curve (AUC) of 0.885, the ApoA1/HDL-C ratio predicts CAD among patients with T2D with a sensitivity of 75% and a specificity of 91% (p-value

Abstract This paper introduces a novel data‐driven approach to develop a fault‐tolerant model predictive controller (MPC) for non‐linear systems. By adopting a Koopman operator‐theoretic perspective, the proposed method leverages historical data from the system to construct a data‐driven model that captures the non‐linear behaviour and fault characteristics. The fault influence is addressed through an online estimation of a time‐varying Koopman predictor, which allows for adjusting the MPC control law to counteract the fault effects. This estimation is performed in a higher dimensional Koopman feature space, where the dynamics behave linearly. As a result, the non‐linear fault‐tolerant MPC optimization problem can be replaced with a more practical and feasible linear time‐varying one using the approximated Koopman predictor. Moreover, by incorporating the online update procedure, the time‐varying Koopman predictor can represent the dynamics of the faulty system. Hence, the controller can adapt and compensate for the faults in real‐time, integrating the fault diagnosis module in the MPC framework and eliminating the need for a separate fault detection unit. Finally, the efficacy of the proposed approach is demonstrated through case study results, which highlight the ability of the controller to mitigate faults and maintain desired system behaviour.

Background and Objectives: Colorectal cancer (CRC) is a heterogeneous disease of the colon or rectum arising from adenoma precursors and serrated polyps. Recently, probiotics have been proposed as an effective and potential therapeutic approach for CRC prevention and treatment. Probiotics have been shown to alleviate inflammation by restoring the integrity of the mucosal barrier and impeding cancer progression. Materials and Methods: In this study, we aimed to investigate the immunomodulatory effects of live and UV-killed Bacillus subtilis natto on the inflammatory response in CRC. Caco-2 cells were exposed to various concentrations of live and UV-killed B. subtilis natto, and cell viability was assessed using MTT assay. Gene expression analysis of IL-10, TGF-β, TLR2 and TLR4 was performed using RT-qPCR. Results: Our findings showed that both live and UV-killed B. subtilis natto caused significant reduction in inflammatory response by decreasing the gene expression of TLR2 and TLR4, and enhancing the gene expression of IL-10 and TGF-β in Caco-2 cells as compared to control group. Conclusion: The results of this study suggest that live and UV-killed B. subtilis natto may hold potential as a therapeutic supplement for modulating inflammation in CRC.

Tics peak in late childhood and decline during adolescence. Yet, for some with Tourettes disorder, tics persist into adulthood. We evaluated childhood predictors of adult tic severity and tic impairment, and change over time. Eighty adolescents/adults were evaluated 11 years following a randomized-controlled trial of behavior therapy. An independent evaluator rated tic severity and tic impairment at baseline, posttreatment, and long-term follow-up. At baseline, parents completed demographics/medical history, and youth tic, internalizing, and externalizing symptom ratings. Youth rated premonitory urge severity and family functioning. After controlling for prior tic treatment effects, female sex and higher tic severity predicted higher tic severity in adulthood; and female sex, no stimulant medication use, higher tic severity, and poorer family functioning predicted higher tic impairment. Higher tic severity and premonitory urge severity predicted smaller reductions in tic severity, whereas higher externalizing symptoms predicted greater reduction in tic severity. Female sex predicted smaller reduction in tic impairment, and externalizing symptoms predicted greater reduction in tic impairment. Female sex and childhood tic severity are important predictors of tic severity and tic impairment in adulthood. Family functioning, premonitory urge severity, and tic severity are important modifiable targets for early or targeted intervention to improve long-term outcomes.

Abstract Background The literature describes an inverse association between the values of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). This survey was designed to exhibit the features of people with type 2 diabetes (T2D) who display this inverse association and identify potential contributing factors to having normal HDL-C values. Methods A total of 6127 persons with T2D were assigned to the present survey. Demographic features and clinical status data were compared between subjects with a substantial inverse association of TG and HDL-C and those without. Logistic regressions were performed to ascertain the role of different factors related to normal HDL-C. Moreover, the restricted cubic spline (RCS) functions were conducted to scrutinize the underlying relationships between the studied variables and low HDL-C levels. Results Patients with high TG (150 ≤ TG

Abstract Background Clostridioides difficile infection (CDI) is one of the most common health care-acquired infections. The dramatic increase in antimicrobial resistance of C. difficile isolates has led to growing demand to seek new alternative medicines against CDI. Achillea millefolium L. extracts exhibit strong biological activity to be considered as potential therapeutic agents. In this work, the inhibitory effects of A. millefolium, its decoction (DEC) and ethanol (ETOH) extracts, were investigated on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S) induced inflammation and apoptosis. Methods Phytochemical analysis of extracts was performed by HPLC and GC analysis. The antimicrobial properties of extracts were evaluated against C. difficile RT001. Cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of extracts and Tox-S were examined by MTT assay and microscopy, respectively. Anti-inflammatory and anti-apoptotic effects of extracts were assessed in Tox-S stimulated Caco-2 cells by RT-qPCR. Results Analysis of the phytochemical profile of extracts revealed that the main component identified in both extracts was chlorogenic acid. Both extracts displayed significant antimicrobial activity against C. difficile RT001. Moreover, both extracts at concentration 50 µg/mL had no significant effect on cell viability compared to untreated cells. Pre-treatment of cells with extracts (50 µg/mL) significantly reduced the percentage of Vero cells rounding induced by Tox-S. Also, both pre-treatment and co-treatment of Tox-S stimulated Caco-2 cells with extracts significantly downregulated the gene expression level of IL-8, IL-1β, TNF-α, TGF-β, iNOS, Bax, caspase-9 and caspase-3 and upregulated the expression level of Bcl-2. Conclusion The results of the present study for the first time demonstrate the antimicrobial activity and protective effects of A. millefolium extracts on inflammatory response and apoptosis induced by Tox-S from C. difficile RT001 clinical strain in vitro. Further research is needed to evaluate the potential application of A. millefolium extracts as supplementary medicine for CDI prevention and treatment in clinical setting.

ABSTRACT Introduction This study aimed to assess and compare the prevalence of diabetes complications between men and women with Type 2 diabetes (T2D), as well as how gender relates to these complications. Methods In this cross‐sectional study, complications of diabetes, including coronary artery disease (CAD), retinopathy, neuropathy and diabetic kidney disease (DKD), were evaluated in 1867 participants with T2D. Additionally, baseline characteristics of the individuals, including anthropometric measurements, metabolic parameters and the use of dyslipidaemia drugs and antihyperglycaemic agents, were assessed. Gender differences in complications were examined using the chi‐squared test. Multivariate logistic regression was employed to investigate the relationship between gender and T2D complications, with and without adjusting for the characteristics of the studied population. Results In the studied population, 62.1% had at least one complication, and complications were 33.5% for DKD, 29.6% for CAD, 22.9% for neuropathy and 19.1% for retinopathy. The prevalence of CAD and neuropathy was higher in men. However, DKD and retinopathy were more prevalent among women. Odds ratios of experiencing any complication, CAD and retinopathy in men compared with women were 1.57 (95% CI: 1.27–2.03), 2.27 (95% CI: 1.72–2.99) and 0.72 (95% CI: 0.52–0.98), respectively, after adjusting for demographic factors, anthropometric measures, metabolic parameters and the consumption of dyslipidaemia drugs and antihyperglycaemic agents. Conclusion The prevalence of diabetes complications was significantly higher in men with diabetes, highlighting the need for better treatment adherence. CAD was associated with the male gender, whereas retinopathy was associated with the female gender. Men and women with diabetes should be monitored closely for CAD and retinopathy, respectively, regardless of their age, diabetes duration, anthropometric measures, laboratory findings and medications.

Abstract Background High concentrations of low‐density lipoprotein cholesterol (LDL‐C) have been a known risk factor for cardiovascular diseases. Also, the role of oxidized LDL (ox‐LDL) in forming atherosclerosis plaque has been proven. However, it has not yet been proven that atherogenic LDL‐C by‐products like ox‐LDL will decrease by keeping the LDL levels at the desired level. This study aimed to examine the relationship between LDL‐C and ox‐LDL in different LDL‐C values in patients with type 2 diabetes (T2D). Methods In this cross‐sectional study, 347 patients with T2D who received statins were enrolled. LDL‐C values were defined into four groups as LDL‐C 100 mg/dL in patients with T2D. However, the revealed association of ox‐LDL with TG level and TG/HDL ratio may be considered in the clinic.

Abstract Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal microorganisms and the gut barrier seems to play an important role in pathogenesis of IBS. The current study aimed to investigate the effect of Blastocystis on the gut microbiota profile and the circulation levels of microRNA (mir)-16 of IBS patients compared to healthy subjects. Stool and blood samples were collected from 80 participants including 40 samples from each IBS and healthy group. Upon DNA extraction from stool samples, barcoding region and quantitative real-time PCR were analyzed to investigate Blastocystis and the microbiota profile, respectively. RNA was extracted from serum samples of included subjects and the expression of mir-16 was evaluated using stem-loop protocol and qreal-time PCR. Significant changes between IBS patients and healthy controls was observed in Firmicutes, Actinobacteria, Faecalibacterium, and Alistipes. In IBS patients, the relative abundance of Bifidobacteria was directly correlated with the presence of Blastocystis, while Alistipes was decreased with Blastocystis. Lactobacillus was significantly increased in Blastocystis carriers. In healthy subjects, the relative abundance of Bifidobacteria was decreased, but Alistipes was increased in Blastocystis carriers. The changes in the Firmicutes/Bacteroidetes ratio was not significant in different groups. The relative expression of mir-16 in Blastocystis-negative IBS patients and healthy carriers was significantly overexpressed compared to control group. The presence of Blastocystis, decreased the relative expression of mir-16 in IBS patients compared to Blastocystis-negative IBS patients. The present study revealed that Blastocystis has the ability to change the abundance of some phyla/genera of bacteria in IBS and healthy subjects. Moreover, Blastocystis seems to modulate the relative expression of microRNAs to control the gut atmosphere, apply its pathogenicity, and provide a favor niche for its colonization.

Abstract Gut microbiota dysbiosis is intimately associated with development of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Nevertheless, the gut microbial community during the course of NAFLD and NASH is yet to be comprehensively profiled. This study evaluated alterations in fecal microbiota composition in Iranian patients with NAFLD and NASH compared with healthy individuals. This cross-sectional study enrolled 15 NAFLD, 15 NASH patients, and 20 healthy controls, and their clinical parameters were examined. The taxonomic composition of the fecal microbiota was determined by sequencing the V3-V4 region of 16S rRNA genes of stool samples. Compared to the healthy controls, NAFLD and NASH patients presented reduced bacterial diversity and richness. We noticed a reduction in the relative abundance of Bacteroidota and a promotion in the relative abundance of Proteobacteria in NAFLD and NASH patients. L-histidine degradation I pathway, pyridoxal 5'-phosphate biosynthesis I pathway, and superpathway of pyridoxal 5'-phosphate biosynthesis and salvage were more abundant in NAFLD patients than in healthy individuals. This study examined fecal microbiota dysbiosis in NAFLD and NASH patients and presented consistent results to European countries. These condition- and ethnicity-specific data could provide different diagnostic signatures and therapeutic targets.

Abstract Background This single-center retrospective cohort study aimed to describe the findings and validity of Bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of patients with ACTH-dependent Cushing’s syndrome (CS). Methods Eleven patients underwent BIPSS due to equivocal biochemical tests and imaging results. Blood samples were taken from the right inferior petrosal sinus (IPS), left IPS, and a peripheral vein before and after stimulation with desmopressin (DDAVP). ACTH and prolactin levels were measured. The diagnosis was based on the ACTH ratio between the IPS and the peripheral vein. Also, lateralization of pituitary adenoma in patients with Cushing’s disease (CD) was predicted. No significant complications were observed with BIPSS. Results Based on the pathology report, eight patients had CD, and three had ectopic ACTH syndrome (EAS). Unstimulated BIPSS resulted in a sensitivity of 87.5%, specificity of 100%, PPV of 100%, NPV of 75%, and accuracy of 91%. Stimulated BIPSS resulted in a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. However, pituitary magnetic resonance imaging (MRI) had a lower diagnostic accuracy (sensitivity:62.5%, specificity:33%, PPV:71%, NPV:25%, accuracy:54%). BIPSS accurately demonstrated pituitary adenoma lateralization in 75% of patients with CD. Conclusions This study suggests that BIPSS may be a reliable and low-complication technique in evaluating patients with ACTH-dependent CS who had inconclusive imaging and biochemical test results. The diagnostic accuracy is improved by DDAVP stimulation. Pituitary adenoma lateralization can be predicted with the aid of BIPSS.

BACKGROUND: Liver cirrhosis is a major public health problem, accounting for high rates of morbidity and mortality worldwide. The cirrhosis etiology is a broad and essential step in planning a treatment strategy. Many recent studies have documented that gut microbiome alterations play a vital role in the development and progression of cirrhosis and its complications. Nevertheless, there is insufficient data on the correlation between liver cirrhosis and gut phageome alterations in patients with advanced liver diseases. This study aimed to analyze the taxonomic structure and functional attributes of the gut phageome in six different etiologies of advanced liver cirrhosis. METHODS: We first retrieved metagenomic sequencing data from three datasets of fecal samples taken from cirrhotic patients with various etiologies. Subsequently, several bioinformatics pipelines were used to analyze bacteriophage composition and determine their functionality. RESULTS: A gene catalog of 479,425 non-redundant genes was developed as a reference to measure gene prevalence. The results of the analysis revealed a few significant differences among the cohorts at the phage species level. However, the alternations were more evident as there were more in-depth analyses of the functional resolution of the gut phageome. CONCLUSIONS: Our findings suggest that the functional analysis of the gut phageome would provide meaningful markers to predict the progression of liver cirrhosis and facilitate the development of novel treatment approaches.

Abstract Background Treatment of Helicobacter pylori (H. pylori) infection has become challenging following the development of primary antibiotic resistance. A primary therapeutic regimen for H. pylori eradication includes clarithromycin; however, the presence of point mutations within the 23S rRNA sequence of H. pylori contributes to clarithromycin resistance and eradication failure. Thus, we aimed to develop a rapid and precise method to determine clarithromycin resistance-related point mutations using the pyrosequencing method. Methods and results H. pylori was isolated from 82 gastric biopsy samples and minimal inhibitory concentration (MIC) was evaluated using the agar dilution method. Clarithromycin resistance-associated point mutations were detected by Sanger sequencing, from which 11 isolates were chosen for pyrosequencing. Our results demonstrated a 43.9% (36/82) prevalence in resistance to clarithromycin. The A2143G mutation was detected in 8.3% (4/48) of H. pylori isolates followed by A2142G (6.2%), C2195T (4.1%), T2182C (4.1%), and C2288T (2%). Although the C2195T mutation was only detected by Sanger sequencing, the overall results from pyrosequencing and Sanger sequencing platforms were comparable. Conclusions Pyrosequencing could be used as a rapid and practical platform in clinical laboratories to determine the susceptibility profile of H. pylori isolates. This might pave the way for efficient H. pylori eradication upon detection.