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Animal Models and Experimental Medicine Jun 2024Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant... (Review)
Review
Short-chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein-coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut-brain axis and gut-lung axis, and promoting bone health.
PubMed: 38940192
DOI: 10.1002/ame2.12464 -
Annals of Agricultural and... Jun 2024Women in pathological pregnancy are a group of patients especially exposed to the risk of occurrence of psychological complications. The aim of the study was assessment...
INTRODUCTION AND OBJECTIVE
Women in pathological pregnancy are a group of patients especially exposed to the risk of occurrence of psychological complications. The aim of the study was assessment of the risk of depressive and anxiety disorders, and the relationship between the intensity of symptoms and social support.
MATERIAL AND METHODS
The study group were 300 patients hospitalized in the Department of Pathology of Pregnancy. The study was conducted using the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety and Depression Scale (HADS), the Inventory of Socially Supportive Behaviours (ISSB), and an author-constructed socio-demographic questionnaire.
RESULTS
The level of State Anxiety (STAI) was higher in respondents from the study group, compared to the control group. The level of anxiety (HADS-A) was higher in the control group than in women from the study group. The level of social informational support was higher in those from the control group, compared to those from the study group. The level of emotional support was lower in respondents from the study group, compared to those from the control group. Instrumental support negatively correlated with the symptoms of depression among women in physiological pregnancy. The lack of evaluative support statistically significantly correlated with anxiety among women hospitalized before labour.
CONCLUSIONS
The results obtained suggest the necessity for the substantive preparation of medical and psychological staff employed in departments of pathology of pregnancy to provide proper emotional and informational support for hospitalized women.
Topics: Humans; Female; Pregnancy; Adult; Social Support; Depression; Anxiety; Cross-Sectional Studies; Young Adult; Pregnancy Complications; Surveys and Questionnaires
PubMed: 38940110
DOI: 10.26444/aaem/183424 -
Frontiers in Bioscience (Landmark... Jun 2024Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of... (Comparative Study)
Comparative Study
BACKGROUND
Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized.
METHODS
In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed.
RESULTS
The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected in rats receiving intravenously injected stem cells.
CONCLUSIONS
Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets.
Topics: Animals; Acute Lung Injury; Lipopolysaccharides; Mesenchymal Stem Cell Transplantation; Umbilical Cord; Rats, Sprague-Dawley; Rats; Male; Bronchoalveolar Lavage Fluid; Mesenchymal Stem Cells; Tumor Necrosis Factor-alpha; Injections, Intravenous
PubMed: 38940047
DOI: 10.31083/j.fbl2906217 -
Frontiers in Bioscience (Landmark... May 2024Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence.... (Review)
Review
Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Gastrointestinal Microbiome; Adipose Tissue, Brown; Animals; Insulin Resistance; Fecal Microbiota Transplantation; Obesity
PubMed: 38940030
DOI: 10.31083/j.fbl2906208 -
Journal of Extracellular Biology Feb 2024The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian...
The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian cancer progression and metastasis is largely unknown. In high grade serous ovarian cancer (HGSOC), ascites is the major contributor to peritoneal metastasis. In this study, we identified significantly elevated ISG15 protein expression in HGSOC patient ascites, ascites derived primary ovarian cancer cells (POCCs), POCC small extracellular vesicles (sEVs) as well as metastatic tissue. Our results demonstrates that ISG15 increases exocytosis in ascites-derived POCCs by decreasing the endosome-lysosomal fusion, indicating a key role in sEV secretion. Further, knockdown (KD) of ISG15 resulted in a significant decrease in vesicles secretion from HGSOC cells and mouse models, leading to reduced HGSOC cell migration and invasion. Furthermore, our pre-clinical mouse model studies revealed the influence of vesicular ISG15 on disease progression and metastasis. In addition, knockdown of ISG15 or using the ISG15 inhibitor, DAP5, in combination therapy with carboplatin showed to improve the platinum sensitivity in-vitro and reduce tumour burden in-vivo. We also found that ISG15 expression within sEV represents a promising prognostic marker for HGSOC patients. Our findings suggest that ISG15 is a potential therapeutic target for inhibiting progression and metastasis in HGSOC and that vesicular ISG15 expression could be a promising biomarker in the clinical management of ovarian cancer. : High-grade serous ovarian cancer (HGSOC) has high morbidity and mortality rates, but its progression and metastasis are still poorly understood, and there is an urgent need for early detection and targeted therapies. Our study presents novel findings that implicate ISG15-mediated vesicular proteins in the advancement and spread of HGSOC. These results offer pre-clinical evidence of potential new molecular targets, prognostic markers and therapeutic strategies for HGSOC that could ultimately enhance patient survival.
PubMed: 38939897
DOI: 10.1002/jex2.92 -
Annals of Ibadan Postgraduate Medicine Apr 2024A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well...
BACKGROUND AND OBJECTIVE
A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well as its treatment. Apo-E is a protein that is important in plasma lipid homeostasis and its genetic alleles have been shown to contribute to lipid abnormalities. We examined for the effect of Apo-E gene polymorphisms on plasma lipid levels in PLHIV on protease inhibitor therapy.
METHODS
This was a cross-sectional study conducted among adult persons living with HIV. Lipid profile, Apo-B and Apo-A were measured in fasting plasma. Amplification and analysis of Apo-E genotypes were determined using the Seeplex Apo-E ACE genotyping kit. Differences in quantitative values were compared with non-parametric analysis methods.
RESULTS
Eighty-four persons were recruited into the study, 75% of whom were virally suppressed. The 3 homozygous genotypes had significantly different levels of low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo-B) and Apolipoprotein A1 (Apo-A1). Persons with apo ε2/ε2 had higher LDL-C compared to those with apo ε3/ε3 (3.26 (3.61) mmol/L vs. 2.76 (1.28) mmol/L, p = 0.010). Those with apo ε4/ε4 had lower Apo-A1 compared to those with apo ε3/ε3 (0.84 (0.48) g/dL vs. 1.27 (0.70) g/dL, p =0.009). Compared with the same group, the heterozygous genotype, apo ε2/ε3 had lower triglyceride levels :1.33 (0.65) mmol/ L vs. 1.86 (1.11) mmol/L, p = 0.045.
CONCLUSION
Polymorphisms in the Apo-E gene may have significant influences on plasma lipid and apolipoprotein levels in PLHIV on PI therapy. This may have implications for the assessment of risk for cardiovascular disease.
PubMed: 38939889
DOI: No ID Found -
Frontiers in Pharmacology 2024Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb , is commonly used to treat various diseases. Previous studies have indicated the...
Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb , is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both and , employing multi-omics techniques to explore the potential mechanisms of toxicity. Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.
PubMed: 38939838
DOI: 10.3389/fphar.2024.1393717 -
Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters.Journal of Extracellular Biology Oct 2023Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing...
Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing parameters affect the biochemical composition, release and possibly the function of CCM-derived EVs (CCM-EV). The CCM-EV task force of the Rigor and Standardization Subcommittee of the International Society for Extracellular Vesicles aims to identify relevant cell culturing parameters, describe their effects based on current knowledge, recommend reporting parameters and identify outstanding questions. While some recommendations are valid for all cell types, cell-specific recommendations may need to be established for non-mammalian sources, such as bacteria, yeast and plant cells. Current progress towards these goals is summarized in this perspective paper, along with a checklist to facilitate transparent reporting of cell culturing parameters to improve the reproducibility of CCM-EV research.
PubMed: 38939735
DOI: 10.1002/jex2.115 -
JACC. Advances Apr 2024Maternal mortality is a major public health crisis in the United States. Cardiovascular disease (CVD) is a leading cause of maternal mortality and morbidity. Labor and... (Review)
Review
Maternal mortality is a major public health crisis in the United States. Cardiovascular disease (CVD) is a leading cause of maternal mortality and morbidity. Labor and delivery is a vulnerable time for pregnant individuals with CVD but there is significant heterogeneity in the management of labor and delivery in high-risk patients due in part to paucity of high-quality randomized data. The authors have convened a multidisciplinary panel of cardio-obstetrics experts including cardiologists, obstetricians and maternal fetal medicine physicians, critical care physicians, and anesthesiologists to provide a practical approach to the management of labor and delivery in high-risk individuals with CVD. This expert panel will review key elements of management from mode, timing, and location of delivery to use of invasive monitoring, cardiac devices, and mechanical circulatory support.
PubMed: 38939671
DOI: 10.1016/j.jacadv.2024.100901 -
Journal of Extracellular Biology May 2024Endometriosis is a common gynaecological condition, with a long diagnostic delay. Surgery is required to confirm a diagnosis, highlighting the need for a non-invasive...
Endometriosis is a common gynaecological condition, with a long diagnostic delay. Surgery is required to confirm a diagnosis, highlighting the need for a non-invasive biomarker. Extracellular vesicles (EVs) may have a role in endometriosis pathogenesis, yet there is limited EV biomarker literature available. This study aimed to investigate the feasibility of isolating cervico-vaginal fluid EVs sampled using cervical brushes and vaginal swabs and to compare these methods. After providing informed consent, patients undergoing surgery for suspected endometriosis had cervical brush and vaginal swab samples collected under general anaesthetic. Isolated EVs were characterised through negative stain transmission electron microscopy (TEM), Western blotting (TSG101, CD63, Calnexin, ApoB, Albumin), tunable resistive pulse sensing (TRPS), microBCA assays and RT-qPCR of miRNAs. PCR was performed on samples prior to EV isolation to assess bacteria present in samples. Cervical brush and vaginal swab EVs were intact vesicles with limited co-isolated contaminants. Cervical brushes had higher concentrations of particles compared to match vaginal swabs, although both samples had low concentrations. Protein and miRNA yield were similar between matched samples. PCR demonstrated only a small amount DNA within samples was bacterial (>0.5%). Cervico-vaginal fluids EVs were successfully isolated from cervical brushes and vaginal swabs, demonstrating a new method of sampling reproductive EVs. EV yield from both sample types was low. Similar protein and miRNA levels suggest either sampling method may be suitable for biomarker studies.
PubMed: 38939571
DOI: 10.1002/jex2.153