A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study's aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p < 0.001). Only IBS-SD with probiotic showed a significant rise in serotonin serum levels (p < 0.05). A significantly higher life quality measures were seen in IBS-SD with probiotic, IBS-SD with placebo, and IBS-NM with placebo (p < 0.05). All groups, both placebo and probiotic, reported significant improvement in IBS severity post-intervention with a higher prevalence of remission and mild IBS (p < 0.05). Dual strains lactobacillus-containing cultured milk drink via its regulation of relevant biomarkers, is a potential anti-depressive prophylactic agent for IBS patients at risk.

The Relationship Between Gut Microbiome Estrobolome and Breast Cancer: A Systematic Review of Current Evidences.

Breast cancer is the most frequent kind of cancer and the second leading cause of mortality worldwide, behind heart disease. Next-generation sequencing technologies enables for unprecedented enumeration of human resident gut microorganisms, conferring novel insights into the role of the microbiota in health and individuals with breast cancer. A growing body of research on microbial dysbiosis seems to indicate an elevated risk of health complications including cancer. Although several dysbiosis indices have been proposed, their underlying methodology, as well as the cohorts and conditions of breast cancer patients are significantly different. To date, these indices have not yet been thoroughly reviewed especially when it comes to researching the estrogen-gut microbiota axis. Instead of providing a thorough rating of the most effective diversity measurements, the current work aims to be used to assess the relevance of each study's findings across the demographic data, different subtypes, and stages of breast cancer, and tie them to the estrobolome, which controls the amount of oestrogen that circulates through humans. This review will cover 11 studies which will go into a detailed discussion for the microbiome results of the mentioned studies, leaving to the user the final choice of the most suited indices as well as highlight the observed bacteria found to be related to the estrobolome in hopes of giving the reader a better understanding for the biological cross-talk between gut microbiome and breast cancer progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01135-z.

Methods for identification of the opportunistic gut mycobiome from colorectal adenocarcinoma biopsy tissues.

Colorectal cancer poses a significant threat to global health, necessitating the development of effective early detection techniques. However, the potential of the fungal microbiome as a putative biomarker for the detection of colorectal adenocarcinoma has not been extensively explored. We analyzed the viability of implementing the fungal mycobiome for this purpose. Biopsies were collected from cancer and polyp patients. The total genomic DNA was extracted from the biopsy samples by utilizing a comprehensive kit to ensure optimal microbial DNA recovery. To characterize the composition and diversity of the fungal mycobiome, high-throughput amplicon sequencing targeting the internal transcribed spacer 1 (ITS1) region was proposed. A comparative analysis revealed discrete fungal profiles among the diseased groups. Here, we also proposed pipelines based on a predictive model using statistical and machine learning algorithms to accurately differentiate colorectal adenocarcinoma and polyp patients from normal individuals. These findings suggest the utility of gut mycobiome as biomarkers for the detection of colorectal adenocarcinoma. Expanding our understanding of the role of the gut mycobiome in disease detection creates novel opportunities for early intervention and personalized therapeutic strategies for colorectal cancer.•Detailed method to identify the gut mycobiome in colorectal cancer patients using ITS-specific amplicon sequencing.•Application of machine learning algorithms to the identification of potential mycobiome biomarkers for non-invasive colorectal cancer screening.•Contribution to the advancement of innovative colorectal cancer diagnostic methods and targeted therapies by applying gut mycobiome knowledge.

Roles of phosphatidylinositol-3-kinases signaling pathway in inflammation-related cancer: Impact of rs10889677 variant and buparlisib in colitis-associated cancer.

BACKGROUND: Phosphatidylinositol-3-kinases (PI3K) is a well-known route in inflammation-related cancer. Recent discovery on PI3K-related genes revealed a potential variant that links ulcerative colitis (UC) and colorectal cancer (CRC) with colitis-associated cancer (CAC). PI3K/AKT pathway has been recommended as a potential additional therapeutic option for CRC due to its substantial role in modifying cellular processes. Buparlisib is a pan-class I PI3K inhibitor previously shown to reduce tumor growth. AIM: To investigate the regulation of rs10889677 and the role of buparlisib in the PI3K signaling pathway in CAC pathogenesis. METHODS: Genomic DNA from 32 colonic samples, including CAC (n = 7), UC (n = 10) and CRC (n = 15), was sequenced for the rs10889677 mutation. The mutant and wildtype fragments were amplified and cloned in the pmirGLO vector. The luciferase activity of cloned vectors was assessed after transfection into the HT29 cell line. CAC mice were induced by a mixture of a single azoxymethane injection and three cycles of dextran sulphate sodium, then buparlisib was administered after 14 d. The excised colon was subjected to immunohistochemistry for Ki67 and Cleaved-caspase-3 markers and quantitative real-time polymerase chain reaction analysis for Pdk1 and Sgk2. RESULTS: Luciferase activity decreased by 2.07-fold in the rs10889677 mutant, confirming the hypothesis that the variant disrupted miRNA binding sites, which led to an increase in IL23R expression and the activation of the PI3K signaling pathway. Furthermore, CAC-induced mice had a significantly higher disease activity index (P < 0.05). Buparlisib treatment significantly decreased mean weight loss in CAC-induced mice (P < 0.05), reduced the percentage of proliferating cells by 5%, and increased the number of apoptotic cells. The treatment also caused a downward trend of Pdk1 expression and significantly decreased Sgk2 expression. CONCLUSION: Our findings suggested that the rs10889677 variant as a critical initiator of the PI3K signaling pathway, and buparlisib had the ability to prevent PI3K-non-AKT activation in the pathophysiology of CAC.

MicroRNAs in Endometriosis: Insights into Inflammation and Progesterone Resistance.

Endometriosis, a non-malignant gynecological disorder influenced by estrogen, involves the growth of endometrial tissue outside the uterus. Its development includes processes such as inflammation, progesterone resistance, angiogenesis, and cell proliferation. Epigenetic factors, particularly the dysregulation of microRNAs (miRNAs), have emerged as key factors in these mechanisms in endometriosis. This review aims to unveil the intricate molecular processes that control inflammation, progesterone resistance, and miRNA functions in endometriosis. In addition, it provides a comprehensive overview of the current understanding regarding the involvement of miRNAs in the inflammatory aspects of this condition. This synthesis encompasses research investigating the molecular underpinnings of inflammation, along with the biogenesis and roles of miRNAs in endometriosis. Furthermore, it examines human studies and functional analyses to establish the intricate connection between miRNAs, inflammation, and progesterone resistance in the context of endometriosis. The results highlight the significant impact of dysregulated miRNAs on the inflammatory pathways and hormonal imbalances characteristic of endometriosis. Consequently, miRNAs hold promise as potential non-invasive biomarkers and targeted therapeutic agents aimed at addressing inflammation and enhancing the response to progesterone treatment in individuals with endometriosis.

Preventative and Therapeutic Effects of Astaxanthin on NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a significant public health issue owing to its high incidence and consequences, and its global prevalence is presently 30% and rising, necessitating immediate action. Given the current controversies related to NAFLD, the search for novel therapeutic interventions continues. Astaxanthin is a carotenoid that primarily originates from marine organisms. It is the best antioxidant among carotenoids and one of the most significant components in treating NAFLD. The use of astaxanthin, a xanthophyll carotenoid, as a dietary supplement to treat chronic metabolic diseases is becoming more evident. According to growing data, astaxanthin may be able to prevent or even reverse NAFLD by reducing oxidative stress, inflammation, insulin resistance, lipid metabolism, and fibrosis. Astaxanthin might become a viable therapeutic or treatment option for NAFLD in the upcoming years. Elucidating the impact and mechanism of astaxanthin on NAFLD would not only establish a scientific basis for its clinical application, but also potentially enhance the precision of experimental methodology for future investigations targeting NAFLD treatment. This review explores the potential preventive and therapeutic effects of astaxanthin on liver disorders, especially NAFLD.

A Review of the Effects of Fucoxanthin on NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease. Fucoxanthin, a red-orange marine carotenoid, is found in natural marine seaweeds with high antioxidant activity and several other remarkable biological features. The aim of this review is to gather evidence of the positive benefits of fucoxanthin on NAFLD. Fucoxanthin provides an extensive list of physiological and biological properties, such as hepatoprotective, anti-obesity, anti-tumor, and anti-diabetes properties, in addition to antioxidant and anti-inflammatory properties. This review focuses on published research on the preventative effects of fucoxanthin on NAFLD from the perspective of human clinical trials, animal experiments in vivo, and in vitro cell investigations. Using a variety of experimental designs, including treatment dosage, experiment model, and experimental periods, the positive effects of fucoxanthin were demonstrated. Fucoxanthin's biological activities were outlined, with an emphasis on its therapeutic efficacy in NAFLD. Fucoxanthin showed beneficial effects in modulating lipid metabolism, lipogenesis, fatty acid oxidation, adipogenesis, and oxidative stress on NAFLD. A deeper comprehension of NAFLD pathogenesis is essential for the development of novel and effective therapeutic strategies.

The impact of diet and ethnicity on gut microbiota variation in irritable bowel syndrome: A multi-center study.

BACKGROUND AND AIM: The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients. METHODS: A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes. RESULTS: A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P = 0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention. CONCLUSION: Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.

Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review.

Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.

Impact of offspring endothelial function from de novo hypertensive disorders during pregnancy: An evidence-based review.

De novo hypertensive disorders of pregnancy (HDP) which consist of gestational hypertension and preeclampsia affect maternal and offspring morbidity and mortality, and potentially increase the risk of cardiovascular disease in the offspring. It is well known that de novo HDP causes various maternal complications, including cardiovascular diseases, placental abruption and liver and kidney failure. However, there are studies suggesting that offspring of pregnancies complicated by de novo HDP have an increased risk of long-term cardiovascular disease. The endothelium is an important regulator of vascular function, and its dysfunction is highly associated with the development of cardiovascular diseases. Hence, this review aimed to systematically identify articles related to the effect of de novo HDP on the endothelial function of the offspring. A computerized database search was conducted on PubMed, Scopus, and Medline from 1976 until 2022. A total of 685 articles were obtained. We identified another three additional articles through review articles and Google Scholar. Altogether, we used 13 articles for data extraction. All studies reported that endothelial function was impaired in the offspring of de novo HDP. This is most likely attributed to impaired vasodilation, subclinical atherosclerosis formation, inflammation, and dysregulated epigenetic regulation of endothelial functions.

Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis.

Endometriosis is a gynecologic disorder characterized by the presence of endometrial tissues outside the uterine cavity affecting reproductive-aged women. Previous studies have shown that microRNAs and their target mRNAs are expressed differently in endometriosis, suggesting that this molecule may play a role in the development and persistence of endometriotic lesions. microRNA (miRNA), a small non-coding RNA fragment, regulates cellular functions such as cell proliferation, differentiation, and apoptosis by the post-transcriptional modulation of gene expression. In this review, we focused on the dysregulated miRNAs in women with endometriosis and their roles in the regulation of apoptosis. The dysregulated miRNAs and their target genes in this pathophysiology were highlighted. Circulating miRNAs as potential biomarkers for the diagnosis of endometriosis have also been identified. As shown by various studies, miRNAs were reported to be a potent regulator of gene expression in endometriosis; thus, identifying the dysregulated miRNAs and their target genes could help discover new therapeutic targets for treating this disease. The goal of this review is to draw attention to the functions that miRNAs play in the pathophysiology of endometriosis, particularly those that govern cell death.

The Roles of Probiotics in the Gut Microbiota Composition and Metabolic Outcomes in Asymptomatic Post-Gestational Diabetes Women: A Randomized Controlled Trial.

Probiotics are widely used as an adjuvant therapy in various diseases. Nonetheless, it is uncertain how they affect the gut microbiota composition and metabolic and inflammatory outcomes in women who have recently experienced gestational diabetes mellitus (post-GDM). A randomized, double-blind, placebo-controlled clinical trial involving 132 asymptomatic post-GDM women was conducted to close this gap (Clinical Trial Registration: NCT05273073). The intervention (probiotics) group received a cocktail of six probiotic strains from Bifidobacterium and Lactobacillus for 12 weeks, while the placebo group received an identical sachet devoid of living microorganisms. Anthropometric measurements, biochemical analyses, and 16S rRNA gene sequencing results were evaluated pre- and post-intervention. After the 12-week intervention, the probiotics group's fasting blood glucose level significantly decreased (mean difference −0.20 mmol/L; p = 0.0021). The HbA1c, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly different between the two groups (p < 0.05). Sequencing data also demonstrated a large rise in the Bifidobacterium adolescentis following probiotic supplementation. Our findings suggest that multi-strain probiotics are beneficial for improved metabolic and inflammatory outcomes in post-GDM women by modulating gut dysbiosis. This study emphasizes the necessity for a comprehensive strategy for postpartum treatment that includes probiotics to protect post-GDM women from developing glucose intolerance.

Lifting the Veil: Characteristics, Clinical Significance, and Application of ß-2-Microglobulin as Biomarkers and Its Detection with Biosensors.

Because ß-2-microglobulin (ß2M) is a surface protein that is present on most nucleated cells, it plays a key role in the human immune system and the kidney glomeruli to regulate homeostasis. The primary clinical significance of ß2M is in dialysis-related amyloidosis, a complication of end-stage renal disease caused by a gradual accumulation of ß2M in the blood. Therefore, the function of ß2M in kidney-related diseases has been extensively studied to evaluate its glomerular and tubular functions. Because increased ß2M shedding due to rapid cell turnover may indicate other underlying medical conditions, the possibility to use ß2M as a versatile biomarker rose in prominence across multiple disciplines for various applications. Therefore, this work has reviewed the recent use of ß2M to detect various diseases and its progress as a biomarker. While the use of state-of-the-art ß2M detection requires sophisticated tools, high maintenance, and labor cost, this work also has reported the use of biosensor to quantify ß2M over the past decade. It is hoped that a portable and highly efficient ß2M biosensor device will soon be incorporated in point-of-care testing to provide safe, rapid, and reliable test results.

Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

Diet and Pre-Intervention Washout Modifies the Effects of Probiotics on Gestational Diabetes Mellitus: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Dynamic interactions among gestational diabetes mellitus (GDM), gut microbiota, inflammation, oxidative stress, and probiotics are increasingly acknowledged. This meta-analysis aimed to summarize the effects of probiotics in GDM, focusing on lifestyle intervention and pre-intervention washout, in addition to metabolic, inflammation, oxidative stress, and pregnancy outcomes. Three electronic databases (i.e., PubMed, Scopus, and CENTRAL) were searched from inception until October 2020. A meta-analysis was performed, and the effect sizes were reported as either mean differences or odds ratios with 95% confidence intervals. Altogether, 10 randomized controlled trials enrolling 594 participants were included. The meta-analysis indicated that probiotics supplementation effectively reduced fasting plasma glucose by 3.10 mg/dL, and subgroup analyses suggested that the duration of intervention, number of species, pre-intervention washout period, and dietary intervention may determine the effects of probiotics. Probiotics also reduced the level of inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and malondialdehyde), incidence of macrosomia, and newborn hospitalization. In conclusion, this meta-analysis suggests that probiotics may have positive effects on metabolic, inflammation, oxidative stress, and neonatal outcomes in women with GDM. Additionally, diet and pre-intervention washout may modify the effects of probiotics. Future studies are warranted on a larger scale to ascertain the clinical significance.

Gut Microbiota Signature Among Asian Post-gestational Diabetes Women Linked to Macronutrient Intakes and Metabolic Phenotypes.

Aberrant gut microbiota dysbiosis in women with a previous history of gestational diabetes mellitus (post-GDM) was comparable to that in adults with type 2 diabetes mellitus (T2DM). Nonetheless, potential relationships between diet, gut microbiota, and metabolic phenotypes in post-GDM women after delivery are yet to be discovered. In this research, we assessed the relationship of the macronutrient intakes, gut microbiota composition, and metabolic phenotypes (i.e., anthropometrics and glycemic control) in post-GDM women with and without postpartum glucose intolerance (GI). About 24 post-GDM women were included in this study, 14 women were grouped in the GI group and 10 women were grouped in the normal glucose tolerance (NGT) group according to oral glucose tolerance test. Macronutrient intake assessment using a 3-day dietary record, anthropometric measurements, biochemical analyses, and fecal sampling were done during 3-6 months postpartum. Gut microbiota profiling was determined using 16S rRNA genes sequencing targeting the V3-V4 regions. The relationships between macronutrient intakes, gut microbiota composition, and metabolic phenotypes were evaluated using Pearson's correlation coefficient and stepwise regression analyses. In this study, most post-GDM women had significantly poor dietary fiber adherence than the nutritional recommendations. Women from the GI group have significantly higher fasting blood glucose (FBG), HbA1c, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels compared to the NGT group. The group also showed significant elevation of high-sensitivity C-reactive protein (hs-CRP) level when compared to the normal value. Specific gut microbial taxa derived from Proteobacteria and Bacteroidetes such as Parasutterella, Aquicella, Haliscomenobacter, and Prevotellaceae_NK3B31_group were significantly abundant in the GI group compared to the NGT group. Prevotellaceae_NK3B31_group was significantly associated with high FBG, HOMA-IR, and HbA1c levels. Low fiber and monounsaturated fatty acids intakes were associated with Lactobacillus. Meanwhile, Lactobacillus was associated with high body mass index, waist circumference, 2-h postprandial blood glucose, and hs-CRP levels. Our study suggested that macronutrient intake is an important predictor of gut microbiota dysbiosis and is associated with obesity, low-grade inflammation, and poor glycemic control in post-GDM women. Hence, dietary intake modification to remodel gut microbiota composition is a promising T2DM preventive strategy in post-GDM women.

Possible Hepatoprotective Effect of Tocotrienol-Rich Fraction Vitamin E in Non-alcoholic Fatty Liver Disease in Obese Children and Adolescents.

Obesity has become a worldwide health concern among the pediatric population. The prevalence of non-alcoholic fatty liver disease (NAFLD) is growing rapidly, alongside the high prevalence of obesity. NAFLD refers to a multifactorial disorder that includes simple steatosis to non-alcoholic steatohepatitis (NASH) with or devoid of fibrosis. NAFLD is regarded as a systemic disorder that influences glucose, lipid, and energy metabolism with hepatic manifestations. A sedentary lifestyle and poor choice of food remain the major contributors to the disease. Prompt and timely diagnosis of NAFLD among overweight children is crucial to prevent the progression of the condition. Yet, there has been no approved pharmacological treatment for NAFLD in adults or children. As indicated by clinical evidence, lifestyle modification plays a vital role as a primary form of therapy for managing and treating NAFLD. Emphasis is on the significance of caloric restriction, particularly macronutrients (fats, carbohydrates, and proteins) in altering the disease consequences. A growing number of studies are now focusing on establishing a link between vitamins and NAFLD. Different types of vitamin supplements have been shown to be effective in treating NAFLD. In this review, we elaborate on the potential role of vitamin E with a high content of tocotrienol as a therapeutic alternative in treating NAFLD in obese children.

Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3'-Untranslated Region of DLC1.

High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3'-untranslated region (3'UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3'UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488-1495 bp of 3'UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes.

Prevalence of Subthreshold Depression Among Constipation-Predominant Irritable Bowel Syndrome Patients.

Patients suffering from irritable bowel syndrome (IBS) may have some form of affective disorders that may worsen their symptoms. Lack of screening among IBS patients is one of the reasons for depression unawareness among healthcare providers. The present study was conducted to evaluate the prevalence of depression among patients with constipation-predominant IBS (IBS-C). A total of 240 IBS patients who fulfilled Rome III criteria were enrolled. The psychiatric assessment was evaluated using the Center for Epidemiologic Studies Depression Scale Revised (CESD-R). Twenty items in CESD-R scale measured symptoms of depression in nine separate groups. Patients were categorized into five different subgroups: major depressive episode, probable major depressive episode, possible major depressive episode, subthreshold depressive symptoms, and without clinical significance of depression. Out of the 240 patients with IBS-C, the majority (n = 161, 67.1%) had no clinical significance of depression. Seventy seven (32.1%) had subthreshold depression and only two (0.83%) patients were regarded as having probable a major depressive episode. No patient was categorized into a major or possible major depressive episode. The prevalence of subthreshold depression was the highest among female (72.3%) patients with 51.1% being single, 44.7% were married, and 4.3% were divorcees. When stratified according to ethnicity, subthreshold depression was highly prevalent among Malays (76.6%), followed by Chinese (19.2%), and Indians (2.1%). A high percentage of the patients were found to be non-smokers (93.6%) and had lower income of less than RM 5000 (USD 1250) per month (89.4%). The moderately high prevalence of subthreshold depression among patients with IBS, justifies psychological evaluation in all patients with functional gastrointestinal disorders.

Gut Microbiota and Gestational Diabetes Mellitus: A Review of Host-Gut Microbiota Interactions and Their Therapeutic Potential.

Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance recognized during pregnancy. GDM is associated with metabolic disorder phenotypes, such as obesity, low-grade inflammation, and insulin resistance. Following delivery, nearly half of the women with a history of GDM have persistent postpartum glucose intolerance and an increased risk of developing type 2 diabetes mellitus (T2DM), as much as 7-fold. The alarming upward trend may worsen the socioeconomic burden worldwide. Accumulating evidence strongly associates gut microbiota dysbiosis in women with GDM, similar to the T2DM profile. Several metagenomics studies have shown gut microbiota, such as Ruminococcaceae, Parabacteroides distasonis, and Prevotella, were enriched in women with GDM. These microbiota populations are associated with metabolic pathways for carbohydrate metabolism and insulin signaling, suggesting a potential "gut microbiota signature" in women with GDM. Furthermore, elevated expression of serum zonulin, a marker of gut epithelial permeability, during early pregnancy in women with GDM indicates a possible link between gut microbiota and GDM. Nevertheless, few studies have revealed discrepant results, and the interplay between gut microbiota dysbiosis and host metabolism in women with GDM is yet to be elucidated. Lifestyle modification and pharmacological treatment with metformin showed evidence of modulation of gut microbiota and proved to be beneficial to maintain glucose homeostasis in T2DM. Nonetheless, post-GDM women have poor compliance toward lifestyle modification after delivery, and metformin treatment remains controversial as a T2DM preventive strategy. We hypothesized modulation of the composition of gut microbiota with probiotics supplementation may reverse postpartum glucose intolerance in post-GDM women. In this review, we addressed gut microbiota dysbiosis and the possible mechanistic links between the host and gut microbiota in women with GDM. Furthermore, this review highlights the potential therapeutic use of probiotics in post-GDM women as a T2DM preventive strategy.