Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia.

Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.

Alterations of gut microbiota-derived metabolites in gestational diabetes mellitus and clinical significance.

BACKGROUND: The change in the characteristics of the gut microbiota is linked to gestational diabetes mellitus (GDM). However, whether and how the gut microbiota-derived metabolites change in GDM is uncertain. Here, we aimed to determine associations between the gut microbiota-derived metabolites and GDM. METHODS: Using targeted metabolomics approaches, 7 types of short-chain fatty acids (SCFAs), 38 types of bile acids (BAs), and 5 types of trimethylamine N-oxide (TMAO), and its derivatives of serum samples were obtained from pregnant women with GDM (n = 24), and healthy pregnant controls (HC, n = 28) were detected to identify the metabolic signature of GDM to investigate the potential biomarkers. Moreover, we assessed the associations between gut microbiota-derived metabolites and clinical parameters. RESULTS: In our study, the gut microbiota-derived metabolites signatures were significantly different between GDM and HC. Quantitative results showed the levels of isobutyric acid, isovaleric acid, valeric acid, caproic acid, GUDCA, THDCA + TUDCA, and LCA-3S were significantly higher in GDM, but the level of TMAO and its derivatives did not change significantly. Some altered gut microbiota-derived metabolites were significantly correlated with glucose and lipid levels. Receiver-operating characteristic (ROC) analysis of generalized linear models showed that gut microbiota-derived metabolites may be potential biomarkers of GDM. CONCLUSION: This study highlights gut microbiota-derived metabolites alterations in GDM and correlation of the clinical indicators, which provides a new direction for future studies aiming to novel serum biomarker for early detection or target of drug therapy of GDM.

Comparative Proteomic Analysis Reveals Antibacterial Mechanism of Patrinia scabiosaefolia Against Methicillin Resistant Staphylococcus epidermidis.

Purpose: As a kind of opportunist pathogen, Staphylococcus epidermidis (MRSE) can cause nosocomial infections and easily evolve into resistant bacteria. Among these, methicillin-resistant Staphylococcus epidermidis (MRSE) exhibit significantly higher rates. Our previous study showed that Patrinia scabiosaefolia (PS) possessed strong antibacterial activity against MRSE. However, the mechanism of PS against MRSE is not clear. Methods: Here, a tandem mass tag-based (TMT) proteomic analysis was performed to elucidate the potential mechanism of PS against MRSE. We compared the differential expression proteins of MRSE under PS stress. Results: Based on a fold change of >1.2 or < 1/1.2 (with p value set at <0.05), a total of 248 proteins (128 up-regulated proteins, 120 down-regulated proteins) were identified. Bioinformatic analysis showed that proteins including arginine deiminase (arcA), ornithine carbamoyltransferase (arcB) and carbamate kinase (arcC), serine-tRNA ligase (serS), phenylalanine-tRNA ligase beta and subunit (pheT), DltD (dlt), d-alanyl carrier protein (dlt), accumulation-associated protein (SasG), serine-aspartate repeat-containing protein C (SdrC) and hemin transport system permease protein HrtB (VraG) played important roles in mechanism of PS against MRSE. Conclusion: In summary, these results indicated that arginine deiminase pathway (ADI) pathway, protein synthesis, cell wall synthesis, biofilm formation and uptake of iron were related to mechanisms of PS against MRSE. Our findings provide an insight into the the mechanism of PS against MRSE, and may be valuable in offering new targets to develop more anti-MRSE drugs.

Proteomic Analysis of the Antibacterial Effect of Improved Dian Dao San against Propionibacterium acnes.

Propionibacterium acnes (P. acnes) is a major pathogen of acne vulgaris. The traditional Chinese medicine (TCM) compound prescription, Dian Dao San (DDS), is effective for treating P. acnes. Previous clinical work by our team demonstrated that improved Dian Dao San (IDDS) has better antibacterial effects. However, the mechanism of IDDS inhibition of P. acnes is still unknown. Hence, the isobaric tags for relative and absolute quantitation (iTRAQ) technology was applied to explore the antibacterial mechanism of IDDS against P. acnes. Our results suggested that the antibacterial mechanism of IDDS was related to the glycolytic pathway. gap, pgk, and tpiA enzymes were found to be potential target proteins in the bacterial glycolytic pathway as an antibacterial mechanism of inhibition. In addition, SEM and TEM analyses revealed that IDDS may destruct bacterial plasma membrane and cell wall. The results provide a reliable, direct, and scientific theoretical basis for wide application of IDDS.

Expression and clinical significance of short-chain fatty acids in pregnancy complications.

Objective: To investigate the expression of short-chain fatty acids (SCFAs)-metabolites of intestinal flora-in gestational complications of gestational diabetes mellitus (GDM), preeclampsia (PE), and intrahepatic cholestasis of pregnancy (ICP), and its clinical significance. Methods: Targeted metabonomics was used to detect SCFAs in the serum of 28 GDM pregnant women, 28 PE pregnant women, 29 ICP pregnant women, and 27 healthy pregnant women (NP); their expression changes were observed; the correlation between SCFAs and clinical characteristics was studied; and their potential as biomarkers for clinical diagnosis was evaluated. Results: There were significant differences in the SCFA metabolic spectrum between the GDM, PE, ICP, and NP groups. Quantitative analysis showed that the content of isobutyric acid in the three pregnancy complications groups (the GDM, PE, and ICP groups) was significantly higher than that in the NP group (p < 0.05), and other SCFAs also showed significant differences in the three pregnancy complications groups compared with the NP group (p < 0.05). Receiver operating characteristic (ROC) curve analysis of the generalized linear model showed that multiple SCFAs were highly sensitive and specific as diagnostic markers in the pregnancy complications groups, where isobutyric acid was highly predictive in GDM (area under the ROC curve (AUC) = 0.764) and PE (AUC = 1), and caproic acid was highly predictive in ICP (AUC = 0.968), with potential clinical application. Conclusion: The metabolic products of intestinal flora, SCFAs, during pregnancy are closely related to pregnancy complications (GDM, PE, and ICP), and SCFAs can be used as potential markers of pregnancy complications.

Research progress in the role of gut microbiota and its metabolites in intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a liver disease that occurs during pregnancy. While ICP has a minimal impact on the mother, it primarily affects the pregnancy outcome of fetus, resulting in spontaneous miscarriage and even the intrauterine death of fetus. AREAS COVERED: This review covers current progress in the role of gut microbiota and bile acids in ICP. EXPERT OPINION: The causes and pathogenesis of ICP are currently unclear, and the serum bile acid level is the main clinical evidence for ICP diagnosis. The gastrointestinal tract is home to a tremendous number and type of microbes, which play critical roles in the synthesis and metabolism of bile acids. Studies in recent years have shown that the changes in gut microbiota and bile acid metabolic profiles are closely associated with ICP. This review discusses some of the future prospects in this area of research.

A Simulation Analysis of Maternal Pelvic Floor Muscle.

Pelvic floor disorder (PFD) is a common disease affecting the quality of life of middle-aged and elderly women. Pelvic floor muscle (PFM) damage is related to delivery mode, fetal size, and parity. Spontaneous vaginal delivery causes especially great damage to PFM. The purpose of this study was to summarize the characteristics of PFM action during the second stage of labor by collecting female pelvic MRI (magnetic resonance imaging) data and, further, to try to investigate the potential pathogenetic mechanism of PFD. A three-dimensional model was established to study the influence factors and characteristics of PFM strength. In the second stage of labor, the mechanical responses, possible damage, and the key parts of postpartum lesions of PFM due to the different fetal biparietal diameter (BPD) sizes were analyzed by finite element simulations. The research results showed that the peak stress and strain of PFM appeared at one-half of the delivery period and at the attachment point of the pubococcygeus to the skeleton. In addition, during the simulation process, the pubococcygeus was stretched by about 1.2 times and the levator ani muscle was stretched by more than two-fold. There was also greater stress and strain in the middle area of the levator ani muscle and pubococcygeus. According to the statistics, either being too young or in old maternal age will increase the probability of postpartum PFM injury. During delivery, the entire PFM underwent the huge deformation, in which the levator ani muscle and the pubococcygeus were seriously stretched and the attachment point between the pubococcygeus and the skeleton were the places with the highest probability of postpartum lesions.

Polyethyleneimine-functionalized Fe3O4/attapulgite particles for hydrophilic interaction-based magnetic dispersive solid-phase extraction of fluoroquinolones in chicken muscle.

Fluoroquinolone (FQ) residues in foods of animal origin may threaten public health but are challenging to determine because of their low contents and complex matrices. In this study, novel polyethyleneimine-functionalized Fe3O4/attapulgite magnetic particles were prepared by a simple co-mixing method and applied as hydrophilic sorbents for the magnetic dispersive solid-phase extraction (MSPE) of three FQs, i.e., ciprofloxacin, norfloxacin, and enrofloxacin, from chicken muscle samples. The preparation of the magnetic particles was of high reproducibility and the products could be reused many times with high adsorption capacity. The key experimental factors possibly influencing the extraction efficiencies, including sample solution, extraction time, sample loading volume, desorption solution, desorption time, and elution volume were investigated. Under optimum MSPE conditions, the analytes in chicken muscle samples were extracted and then determined by RPLC-MS/MS in MRM mode. Good linearity was obtained for the analytes with correlation coefficients ranged from 0.9975 to 0.9995. The limits of detection were in the range of 0.02-0.08 µg kg-1, and the recoveries of the spiked FQs in chicken muscle samples ranged from 83.9 to 98.7% with relative standard deviations of 1.3-6.8% (n = 3). Compared with the traditional MSPE methods based on hydrophobic mechanism, this hydrophilic interaction-based method significantly simplifies the sample pretreatment procedure and improves repeatability. This method is promising for accurate monitoring of FQs in foods of animal origin.

Dichondra repens J.R.Forst. and G.Forst.: A Review of Its Traditional Uses, Chemistry, Pharmacology, Toxicology and Applications.

Ethnopharmacology relevance: Dichondra repens J.R.Forst. and G.Forst (DRF; Convolvulaceae, called Matijin in Chinese), has been traditionally used to treat jaundice, bacillary dysentery, urinary tract infection, edema, contusions, and strains and sprains based on traditional Chinese medicine (TCM) concepts. Aim of study: This paper intends to provide a comprehensive and critical analysis of research on DRF focusing on a relationship between traditional uses and pharmacological effects, evaluating the therapeutic potential of this plant. Methods: Relevant data on DRF were retrieved from available databases. Results: The heat-clearing and detoxifying, and removing the phlegm and turbid urine effects of DRF are linked to its anti-hepatitis B virus (HBV), anti-inflammatory, and hepatoprotective activities. Especially, the hepatoprotective effects of DRF are mainly based on anti-HBV activities of phenylalanine dipeptides Matijin-Su (MTS) and its derivatives derived from this plant. Further, a phase I anti-HBV clinical trial of a candidate compound named bentysrepinine (Y101, Chinese name Tifentai) has been completed. Also, anti-tumor, analgesic, and antibacterial properties have been reported in the extracts and compounds from DRF. Although pharmacy, pharmacodynamics, toxicology, and pharmacokinetics of bentysrepinine have been systemically reported, no studies have reported chemistry, safety, pharmacology of other compounds or extracts systemically. Conclusion: Phenylalanine dipeptide compounds are main components and MTS is a characteristic substance of DRF. The main pharmacological effect of DRF is anti-HBV activity, which is coherent with the traditional use of this plant in China. Except bentysrepinine, few studies have been conducted on toxicities of the extracts or compounds from DRF. Thus, it is still necessary to evaluate safety, chemistry, pharmacology of the extracts or compounds from DRF regarding the link between traditional uses and modern applications before the future clinical trials. Bacterial sepsis, cholecystitis and tumors may be prior therapeutic targets of this plant in the future.