The Circulating CDC42 Expression in Sepsis: Relation to Disease Susceptibility, Inflammation, Multiple Organ Dysfunctions and Mortality Risk.

OBJECTIVE: Cell division cycle 42 (CDC42) modulates inflammation and multiple organ dysfunction by regulating T-cell differentiation and macrophage polarization. This research intended to explore the association of blood CDC42 expression with septic risk, multi-organ dysfunctions, and mortality. METHODS: 145 sepsis patients and 50 health controls were recruited, then CDC42 expression in peripheral blood mononuclear cell (PBMC) from them was measured by RT-qPCR. RESULTS: CDC42 was decreased in sepsis patients versus health controls (P<0.001); meanwhile, the receiver operating characteristic (ROC) curve showed that CDC42 had a certain value to predict sepsis risk with an area under the curve (AUC) (95% confidence interval (CI): 0.797 (0.725-0.869). Furthermore, CDC42 was negatively correlated with C-reactive protein (P<0.001), tumor necrosis factor-alpha (P<0.001) and interleukin-17A (P<0.001) but less with interleukin-6 (P=0.056). Moreover, CDC42 was negatively related to the SOFA score (P<0.001) and its several subscales (respiratory system, liver, cardiovascular, and renal system) (P<0.05). Furthermore, CDC42 was lower in septic deaths versus survivors (P<0.001); meanwhile, the ROC curve exhibited a certain ability of CDC42 in estimating 28-day mortality with an AUC (95%CI) of 0.766 (0.676-0.855). CONCLUSION: Circulating CDC42 exhibits potency to be a prognostic biomarker reflecting multi-organ dysfunctions and higher mortality risk in sepsis.

How mitochondrial dynamics imbalance affects the progression of breast cancer:a mini review.

Despite the high incidence of breast cancer in women worldwide, there are still great challenges in the treatment process. Mitochondria are highly dynamic organelles, and their dynamics involve cellular energy conversion, signal conduction and other processes. In recent years, an increasing number of studies have affirmed the dynamics of mitochondria as the basis for cancer progression and metastasis; that is, an imbalance between mitochondrial fission and fusion may lead to the progression and metastasis of breast cancer. Here, we review the latest insights into mitochondrial dynamics in the progression of breast cancer and emphasize the clinical value of mitochondrial dynamics in diagnosis and prognosis, as well as important advances in clinical research.

The Effect of Inspiratory Muscle Training on Health-Related Fitness in College Students.

In an era characterized by rapid economic growth and evolving lifestyles, college students encounter numerous challenges, encompassing academic pressures and professional competition. The respiratory muscle endurance capability is important for college students during prolonged aerobic exercise. Therefore, it is of great significance to explore an effective intervention to enhance the endurance level of college students. This study explores the transformative potential of inspiratory muscle training (IMT) to improve the physical functions of college students. This research comprised a group of 20 participants who underwent IMT integrated into their daily physical education classes or regular training sessions over an 8-week period, with 18 participants forming the control group. The IMT group adhered to the manufacturer's instructions for utilizing the PowerBreathe device. The findings indicated a significant positive effect on inspiratory muscle strength (p < 0.001), showing improvements in pulmonary function, exercise tolerance, cardiac function, and overall athletic performance. These results revealed the substantial benefits of IMT in enhancing physical fitness and promoting health maintenance among college students.

Establishment of an amplification strategy - specific binding - convenient processing integrated aflatoxin B1 detection method based on Fe3O4-NH4/AuNPs/apt-S1.

Aflatoxin B1 (AFB1) is a potent toxin in food, necessitating rapid, instant, and sensitive detection. We have engineered an electrochemical sensor to monitor AFB1 using a system composed of Fe3O4-NH4/AuNPs/apt-S1. The aptamer specifically recognizes AFB1, while 'S1' is functionalized with methylene blue to enhance the current. The RecJf exonuclease promotes the formation of the electrochemical strategy. The Fe3O4 component, with its magnet properties, enables a rapid separation of solids and liquids without the need for instrumentation. The sensor exhibits a linear range for AFB1 ranging from 1 ng to 10 µg. The regression equation is I(nA) = 446.8 × logc+2085 (where I and c represent the peak current and AFB1 concentration, respectively). The correlation coefficient is 0.9508, and the detection limit is 3.447 nM. The relative standard deviation of AFB1 in peanut oil ranges from 4.80% to 6.80%. These results demonstrate that the sensor has high sensitivity, stability, repeatability, and specificity for AFB1 detection.

MiR-378 Inhibits Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting AKT2.

Cardiomyocyte hypertrophy plays a crucial role in heart failure development, potentially leading to sudden cardiac arrest and death. Previous studies suggest that micro-ribonucleic acids (miRNAs) show promise for the early diagnosis and treatment of cardiomyocyte hypertrophy.To investigate the miR-378 expression in the cardiomyocyte hypertrophy model, reverse transcription-polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence tests were conducted in angiotensin II (Ang II)-induced H9c2 cells and Ang II-induced mouse model of cardiomyocyte hypertrophy. The functional interaction between miR-378 and AKT2 was studied by dual-luciferase reporter, RNA pull-down, Western blot, and RT-qPCR assays.The results of RT-qPCR analysis showed the downregulated expression of miR-378 in both the cell and animal models of cardiomyocyte hypertrophy. It was observed that the introduction of the miR-378 mimic inhibited the hypertrophy of cardiomyocytes induced by Ang II. Furthermore, the co-transfection of AKT2 expression vector partially mitigated the negative impact of miR-378 overexpression on Ang II-induced cardiomyocytes. Molecular investigations provided evidence that miR-378 negatively regulated AKT2 expression by interacting with the 3' untranslated region (UTR) of AKT2 mRNA.Decreased miR-378 expression and AKT2 activation are linked to Ang II-induced cardiomyocyte hypertrophy. Targeting miR-378/AKT2 axis offers therapeutic opportunity to alleviate cardiomyocyte hypertrophy.

Injectable chitosan-polyvinylpyrrolidone composite thermosensitive hydrogels with sustained submucosal lifting for endoscopic submucosal dissection.

To develop a submucosal injection material with sustained submucosal lifting for endoscopic submucosal dissection (ESD), this study designed and prepared a novel composite thermosensitive hydrogel system with high pH chitosan-polyvinylpyrrolidone-ß-glycerophosphate (HpHCS-PVP-GP). HpHCS improved the injectability of the hydrogels and retained the rapid gelation ability at low concentrations. The modification of PVP significantly improved the stability of low-temperature hydrogel precursor solutions and the integrity of hydrogels formed at 37 °C through hydrogen bonds between PVP and HpHCS. A mathematical model was established using response surface methodology (RSM) to evaluate the synergistic effect of HpHCS, GP, and PVP concentrations on gelation time. This RSM model and submucosal lifting evaluation using in vitro pig esophageal models were used to determine the optimal formula of HpHCS-PVP-GP hydrogels. Although the higher PVP concentration (5 % (w/v)) prolonged gelation time, it improved hydrogel mechanical strength, resulting in better submucosal lifting performance. The experiments of Bama mini pigs showed that the heights of the cushions elevated by the HpHCS-5%PVP-GP hydrogel remained about 80 % 1 h after injection. Repeated injections were avoided, and the hydrogel had no cytotoxicity after electric cutting. Therefore, the HpHCS-PVP-GP thermosensitive hydrogel might be a promising submucosal injection material for ESD.

TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.

Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.

Metabolomics analysis reveals the effect of fermentation on the chemical composition and antioxidant activity of Paeonia lactiflora Root.

Fermentation is an effective means of enhancing the nutritional value of natural medicines, however, it is unclear how the metabolites changed during the fermentation of Paeonia lactiflora root (PLR). This study intends to elucidate how the active constituents and antioxidant activity of PLR change during fermentation. The study examined the levels of total glucosides of paeony (TGP), total flavonoids content (TFC), total phenols content (TPC), and antioxidant capability by high performance liquid chromatography (HPLC) and spectrophotometry. The chemical compositions before and after PLR fermentation were compared utilizing ultra-high performance liquid chromatography-mass spectrometry (UHPLC - MS). The findings from this study indicate that TGP, TFC and TPC peaked at Day 2 of fermentation, and the antioxidant capacity increased after fermentation. Of the 109 detected compounds, 18 were discrepant compounds. In summary, fermentation is an essential strategy for enhancing the functional activity of PLR. The current study could establish a scientific basis for future research on the fermentation of PLR, and provides new insights into the influence of fermentation on chemical composition as well as the antioxidant activity of drugs.

Protective effects of oyster polypeptide on cyclophosphamide-induced immunosuppressed rats.

BACKGROUND: Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (1H-NMR) urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. RESULTS: Oyster polypeptide restored the body weight and the structure of spleen and thymus in rats with cyclophosphamide-induced immunosuppression. It upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as interleukin­6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased the numbers of CD3+ and CD4+ T cells in the immunosuppressed rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urine, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally, a combination of metabolomics and microbiomics found that the metabolism of taurine and hypotaurine, and the metabolism of alanine, aspartate, and glutamate were disturbed, but these metabolic pathways were restored by OP. CONCLUSION: This study demonstrated that OP had immunoprotective effects in rats with cyclophosphamide-induced immunosuppression by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provide a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. © 2024 Society of Chemical Industry.

Novel portable photoelectrochemical sensor based on CdS/Au/TiO2 nanotube arrays for sensitive, non-invasive, and instantaneous uric acid detection in saliva.

Uric acid (UA) monitoring is the most effective method for diagnosis and treatment of gout, hyperuricemia, hypertension, and other diseases. However, challenges remain regarding detection efficiency and rapid on-site detection. Here, we first synthesized a CdS/Au/TiO2-NTAs Z-scheme heterojunction material using a titanium dioxide nanotube array (TiO2-NTAs) as the substrate and modified with gold nanoparticles (Au) and cadmium sulfide particles (CdS). This material achieves bandgap alignment to generate a large number of electron-hole pairs under illumination. Then, using CdS/Au/TiO2-NTAs as the working electrode and molecularly imprinted polymers (MIP) as the recognition unit, we constructed a portable photoelectrochemical (PEC) sensor for non-invasive instant detection of UA concentration in human saliva, which has unique advantages in the field of high-sensitivity PEC instant detection. The portable MIP-PEC sensor achieves a linear range of 0.01-50 µM and a detection limit as low as 5.07 nM (S/N = 3). At the same time, the portable MIP-PEC sensor exhibits excellent sensitivity, specificity as well as stability, and shows no statistically significant difference compared to traditional high-performance liquid chromatography (HPLC) in practical sample detection. Compared to traditional PEC modes, this work demonstrates a novel and universal method for high-sensitivity instant detection in the field of PEC.

Revealing the degrading-possibility of methyl red by two azoreductases of Anoxybacillus sp. PDR2 based on molecular docking.

Azo dyes, as the most widely used synthetic dyes, are considered to be one of the culprits of water resources and environmental pollution. Anoxybacillus sp. PDR2 is a thermophilic bacterium with the ability to degrade azo dyes, whose genome contains two genes encoding azoreductases (named AzoPDR2-1 and AzoPDR2-2). In this study, through response surface methodology (RSM), when the initial pH, inoculation volume and Mg2+ addition amount were 7.18, 10.72% and 0.1 g/L respectively, the decolorization rate of methyl red (MR) (200 mg/L) could reach its maximum (98.8%). The metabolites after biodegradation were detected by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography mass spectrometry (LC-MS/MS), indicating that MR was successfully decomposed into 4-aminobenzoic acid and other small substrates. In homologous modeling, it was found that both azoreductases were flavin-dependent azoreductases, and belonged to the α/ß structure, using the Rossmann fold. In their docking results with the cofactor flavin mononucleotide (FMN), FMN bound to the surface of the protein dimer. Nicotinamide adenine dinucleotide (NADH) was superimposed on the plane of the pyrazine ring between FMN and the activity pocket of protein. Besides, both azoreductase complexes (azoreductase-FMN-NADH) exhibited a substrate preference for MR. Asn104 and Tyr74 played an important role in the combination of the azoreductase AzoPDR2-1 complex and the azoreductase AzoPDR2-2 complex with MR, respectively. This provided assistance for studying the mechanism of azoreductase biodegradation of azo dyes in thermophilic bacteria.

A comprehensive "quality-quantity-activity" approach based on portable near-infrared spectrometer and membership function analysis to systematically evaluate spice quality: Cinnamomum cassia as an example.

Spices have long been popular worldwide. Besides serving as aromatic and flavorful food and cooking ingredients, many spices exhibit notable bioactivity. Quality evaluation methods are essential for ensuring the quality and flavor of spices. However, existing methods typically focus on the content of particular components or certain aspects of bioactivity. For a systematic evaluation of spice quality, we herein propose a comprehensive "quality-quantity-activity" approach based on portable near-infrared spectrometer and membership function analysis. Cinnamomum cassia was used as a representative example to illustrate this approach. Near-infrared spectroscopy and chemometric methods were combined to predict the geographical origin, cinnamaldehyde content, ash content, antioxidant activity, and integrated membership function value. All the optimal prediction models displayed good predictive ability (correlation coefficient of prediction > 0.9, residual predictive deviation > 2.1). The proposed approach can provide a valuable reference for the rapid and comprehensive quality evaluation of spices.

Quality control for a traditional Chinese medicine, Millettia speciosa Champ, using ultra-high-performance liquid chromatography fingerprint, serum pharmacochemistry and network pharmacology.

Millettia speciosa (M. speciosa) Champ (MSC) is a healthy food type with medicinal and edible homology, which is now considered a clinically significant anti-rheumatoid arthritis medicine. However, there is currently no standardized or generally accepted research strategy by which we can assess M. speciosa. Thus, it is essential to develop novel theories, strategies and evaluation methods for the scientific quality control of M. speciosa. Herein, our use ultra-high-performance liquid chromatography (UPLC)-MS/MS analysis identified 12 common bioactive components absorbed into MSC serum. Next, network pharmacology analysis exhibited that 5 MSC components may be those active components in treating rheumatoid arthritis and may be considered potential quality markers. These 5 components were then quantified using a fast UPLC approach, based on the quality marker of measurability, showing that lenticin can be regarded as the MSC quality marker. The cumulative study findings, based on systematic assessment of chemical composition both in vivo and in vitro, and the potential efficacy of M. speciosa, provide a novel approach for M. speciosa quality control.

The impact and mechanism of TET3 overexpression on the progression of hepatic fibrosis.

Aims: To investigate whether TET3 regulates hepatic stellate cell apoptosis and understand the role of demethylation in hepatic fibrosis (HF). Methods: LX-2T cells were infected with TET3 lentivirus. After TET3 adenovirus infection, the degree of HF in each group was analyzed. Chromatin immunoprecipitation was used to verify the targeting relationship between TET3 and CBP, and finally the expression of various proteins was detected. Results: TET3 overexpression activated the CBP/FOXO1-BIM pathway, increased the expression of apoptotic proteins and accelerated the apoptosis of activated LX-2 cells. The degree of HF was improved in the TET3 upregulation group. Conclusion: TET3 can activate the CBP/FOXO1-BIM pathway to accelerate the apoptosis of activated hepatic stellate cells and ultimately alleviate HF.

Evaluation of aristolochic acid Ι nephrotoxicity in mice via 1H NMR quantitative metabolomics and network pharmacology approaches.

Background: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion: This work provides a meaningful insight for the mechanism of AAΙ renal injury.

Metabolomics and molecular docking analysis of antibiotic exposure in Bifidobacterium adolescentis.

Bifidobacterium adolescentis is a probiotic. This research aimed to investigate the mechanism of antibiotics led to decrease in the number of B. adolescentis. The metabolomics approach was employed to explore the effects of amoxicillin on metabolism of B.adolescentis, while MTT assay and scanning electron microscopy were applied to analyse changes in viability and morphology of bacteria. Molecular docking was used to illuminate the mechanism by which amoxicillin acts on a complex molecular network. The results showed that increasing the concentration of amoxicillin led to a gradual decrease in the number of live bacteria. Untargeted metabolomics analysis identified 11 metabolites that change as a result of amoxicillin exposure. Many of these metabolites are involved in arginine and proline metabolism, glutathione metabolism, arginine biosynthesis, cysteine, and methionine metabolism, and tyrosine and phenylalanine metabolism. Molecular docking revealed that amoxicillin had a good binding effect on the proteins AGR1, ODC1, GPX1, GSH, MAT2A, and CBS. Overall, this research provides potential targets for screening probiotic regulatory factors and lays a theoretical foundation for the elucidation of its mechanisms.

Integrating metabonomics and metagenomics sequencing to study the anti-liver fibrosis effects of palmatine in Corydalis saxicola Bunting.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. AIM OF THE STUDY: To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. MATERIAL AND METHODS: Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. RESULTS: The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. CONCLUSION: The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants.

TET3 as a non-invasive screening tool for the detection of fibrosis in patients with chronic liver disease.

Ten-eleven translocation protein 3 (TET3) is one of the key enzymes in DNA demethylation which can be expressed in liver tissues. However, the clinical value of TET3 for diagnosis and treatment of chronic liver disease have not been reported previously. We investigated the diagnostic accuracy of serum TET3 as a non-invasive screening tool for liver fibrosis. 212 patients with chronic liver disease from were enrolled in this study. Enzyme-linked immunosorbent assay was used to measure the serum levels of TET3. Receiver operating characteristics (ROC) were determined to examine the diagnostic accuracy of TET3 and combination model for diagnosis fibrosis. Serum TET3 level in fibrosis cases was significantly higher than that in non-fibrosis and controls, respectively. The areas under the ROC curve of the TET3 and fibrosis-4 index for liver fibrosis were 0.863 and 0.813, and 0.916 and 0.957 for liver cirrhosis. The combination of TET3 and fibrosis-4 index had a highly promising positive predictive value for detecting liver fibrosis and cirrhosis different stages of (93.5% and 100%) as compared with each diagnostic tool alone. TET3 is related to the development of liver fibrosis and cirrhosis. The TET3-fibrosis-4 model enhances discriminatory power and represents a promising non-invasive tool for the diagnosis and screening of liver fibrosis.

Preventive effect of tilapia skin collagen hydrolysates on ulcerative colitis mice based on metabonomic and 16 S rRNA gene sequencing.

BACKGROUND: Tilapia skin collagen hydrolysates (TSCHs) are the product of enzymatic hydrolysis of collagen, which is mainly extracted from tilapia skin. The components of TSCHs have recently been reported to play a preventive role in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). However, it has not been illustrated whether TSCHs can prevent against DSS-induced UC via the gut microbiota and its derived metabolites. RESULTS: TSCHs are mainly composed of amino acids, which have similar characteristics to collagen, with most having a molecular weight below 5 kDa. In a mouse model of UC, TSCHs had no toxic effect at a dose of 60 g kg-1 and could reduce body weight changes, colon length, histopathological changes and score, and the level of the serum inflammatory cytokine interleukin (IL)-6. Concurrently, 16 S rRNA sequencing showed that TSCHs significantly reduced the abundance of Bacteroidetes and Proteobacteria at the phylum level and norank_f__Muribaculaceae and Escherichia-Shigella at the genus level, while they increased the abundance of Firmicutes at the phylum level and Lachnoclostridium, Allobaculum, Enterorhabdus, and unclassified__f__Ruminococcaceae at the genus level. Target metabolomic analysis showed that TSCHs elevated the concentration of total acid, acetic acid, propanoic acid, and butanoic acid, but reduced isovaleric acid concentrations. Moreover, Pearson correlation analysis revealed that Allobaculum, unclassified_Ruminococcaceae, and Enterorhabdus were positively correlated with acetic acid and butyric acid, but not Escherichia-Shigella. CONCLUSION: These findings suggest that TSCHs can prevent UC by modulating gut microbial and microbiota-derived metabolites. © 2023 Society of Chemical Industry.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.