Assessing the efficacy of tocotrienol-rich fraction vitamin E in obese children with non-alcoholic fatty liver disease: a single-blind, randomized clinical trial.

BACKGROUND: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. TRIAL REGISTRATION: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

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 role of probiotics in improving menstrual health in women with primary dysmenorrhoea: A randomized, double-blind, placebo-controlled trial (the PERIOD study).

BACKGROUND: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea. OBJECTIVE: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea. DESIGN: Randomized placebo-controlled trial. METHODS: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment. RESULTS: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26-1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines. CONCLUSION: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings. REGISTRATION: This study is registered under ClinicalTrials.gov (NCT04119011).

Use of Probiotic in Primary DysmenorrhoeaThis study looked at whether taking probiotics (good bacteria) for 3 months could improve the quality of life and reduce pain in women with painful periods. The study found that probiotics did not significantly improve quality of life scores, but did reduce the use of painkillers and improve mental health scores. However, the probiotics did not have a significant effect on inflammatory markers in the body. More research is needed to confirm the findings.

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.

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.

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.

Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing.

Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, apoptosis, and diabetic vascular endothelial dysfunction. An increasing number of microRNAs (miRNAs) have been found to be involved in the pathogenesis of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemia. Therefore, this study aims to analyze the miRNA profile of human umbilical-vein endothelial cells (HUVECs) exposed to hyperglycemia. HUVECs were divided into two groups: the control (treated with 5.5 mM glucose) and hyperglycemia (treated with 33.3 mM glucose) groups. RNA sequencing identified 17 differentially expressed miRNAs between the groups (p < 0.05). Of these, 4 miRNAs were upregulated, and 13 miRNAs were downregulated. Two of the most differentially expressed miRNAs (novel miR-1133 and miR-1225) were successfully validated with stem-loop qPCR. Collectively, the findings show that there is a differential expression pattern of miRNAs in HUVEC following exposure to hyperglycemia. These 17 differentially expressed miRNAs are involved in regulating cellular functions and pathways related to oxidative stress and apoptosis that may contribute to diabetic vascular endothelial dysfunction. The findings provide new clues on the role of miRNAs in the development of diabetic vascular endothelial dysfunction, which could be useful in future targeted therapy.

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.

The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (-7.9 ± 0.44, p < 0.0001) and TNF-α (-0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: -34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: -33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes.

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.

Dietary Inflammatory Index, Obesity, and the Incidence of Colorectal Cancer: Findings from a Hospital-Based Case-Control Study in Malaysia.

Obesity-mediated inflammation represents a key connection between the intake of foods with high inflammatory potential and colorectal cancer (CRC) risk. We aimed to explore the association between energy-adjusted dietary inflammatory index (E-DII) in relation to CRC risk in both obese and non-obese subjects. This study included 99 histopathologically confirmed CRC cases, 73 colonic polyps cases, and 141 healthy controls from tertiary medical centres in both urban and suburban areas in Peninsular Malaysia. The subjects were categorised into body mass index (BMI) < 25 kg/m2 and BMI ≥ 25 kg/m2 groups. E-DII scores were computed based on dietary intake assessed using a validated food frequency questionnaire (FFQ). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential cofounders. The mean dietary energy intake and mean BMI values of the subjects tended to increase as the E-DII scores increased (p for trend < 0.001). E-DII was significantly related to CRC risk only in obese subjects (OR = 1.45; 95% CI = 1.30-1.77; p < 0.001 for trend). Stratified analyses of risk factors showed significant associations between E-DII and CRC risk by age group (p for interaction = 0.030), smoking status (p for interaction = 0.043), and anthropometric indices for both males and females (p for interaction < 0.001) in the most pro-inflammatory E-DII quartile vs. the lowest E-DII quartile. Overall, pro-inflammatory diets were associated with an increased incidence of CRC in the Malaysian population, particularly in obese subjects.

Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers.

Ovarian cancer is a lethal reproductive tumour affecting women worldwide. The advancement in presentation and occurrence of chemoresistance are the key factors for poor survival among ovarian cancer women. Surgical debulking was the mainstay of systemic treatment for ovarian cancer, which was followed by a successful start to platinum-based chemotherapy. However, most women develop platinum resistance and relapse within six months of receiving first-line treatment. Thus, there is a great need to identify biomarkers to predict platinum resistance before enrolment into chemotherapy, which would facilitate individualized targeted therapy for these subgroups of patients to ensure better survival and an improved quality of life and overall outcome. Harnessing the immune response through immunotherapy approaches has changed the treatment way for patients with cancer. The immune outline has emerged as a beneficial tool for recognizing predictive and prognostic biomarkers clinically. Studying the tumour microenvironment (TME) of ovarian cancer tissue may provide awareness of actionable targets for enhancing chemotherapy outcomes and quality of life. This review analyses the relevance of immunohistochemistry biomarkers as prognostic biomarkers in predicting chemotherapy resistance and improving the quality of life in ovarian cancer.

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.

Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer.

Chronic relapsing inflammatory bowel disease is strongly linked to an increased risk of colitis-associated cancer (CAC). One of the well-known inflammatory carcinogenesis pathways, phosphatidylinositol 3-kinase (PI3K), was identified to be a crucial mechanism in long-standing ulcerative colitis (UC). The goal of this study was to identify somatic variants in the cytokine-induced PI3K-related genes in UC, colorectal cancer (CRC) and CAC. Thirty biopsies (n = 8 long-standing UC, n = 11 CRC, n = 8 paired normal colorectal mucosa and n = 3 CAC) were subjected to targeted sequencing on 13 PI3K-related genes using Illumina sequencing and the SureSelectXT Target Enrichment System. The Genome Analysis Toolkit was used to analyze variants, while ANNOVAR was employed to detect annotations. There were 5116 intronic, 355 exonic, 172 untranslated region (UTR) and 59 noncoding intronic variations detected across all samples. Apart from a very small number of frameshifts, the distribution of missense and synonymous variants was almost equal. We discovered changed levels of IL23R, IL12Rß1, IL12Rß2, TYK2, JAK2 and OSMR in more than 50% of the samples. The IL23R variant in the UTR region, rs10889677, was identified to be a possible variant that might potentially connect CAC with UC and CRC. Additional secondary structure prediction using RNAfold revealed that mutant structures were more unstable than wildtype structures. Further functional research on the potential variants is, therefore, highly recommended since it may provide insight on the relationship between inflammation and cancer risk in the cytokine-induced PI3K pathway.

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.

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.

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.