Mesenchymal stem cell therapy for liver transplantation: clinical progress and immunomodulatory properties.

Although liver transplantation (LT) is an effective strategy for end-stage liver diseases, the shortage of donor organs and the immune rejection hinder its widespread implementation in clinical practice. Mesenchymal stem cells (MSCs) transplantation offers a promising approach for patients undergoing liver transplantation due to their immune regulatory capabilities, hepatic protection properties, and multidirectional differentiation potential. In this review, we summarize the potential applications of MSCs transplantation in various LT scenarios. MSCs transplantation has demonstrated effectiveness in alleviating hepatic ischemia-reperfusion injury, enhancing the viability of liver grafts, preventing acute graft-versus-host disease, and promoting liver regeneration in split LT therapy. We also discuss the clinical progress, and explore the immunomodulatory functions of MSCs in response to both adaptive and innate immune responses. Furthermore, we emphasize the interactions between MSCs and different immune cells, including T cells, B cells, plasma cells, natural killer cells, dendritic cells, Kupffer cells, and neutrophils, to provide new insights into the immunomodulatory properties of MSCs in adoptive cell therapy.

Proteomics analyses of acute kidney injury biomarkers in a rat exertional heat stroke model.

The frequency of exertional heat stroke (EHS) increases with the gradual elevation of global temperatures during summer. Acute kidney injury (AKI) is a common complication of EHS, and its occurrence often indicates the worsening of a patient's condition or a poor prognosis. In this study, a rat model of AKI caused by EHS was established, and the reliability of the model was evaluated by HE staining and biochemical assays. The expression of kidney tissue proteins in the EHS rats was analyzed using label-free liquid chromatography-tandem mass spectrometry. A total of 3,129 differentially expressed proteins (DEPs) were obtained, and 10 key proteins were finally identified, which included three upregulated proteins (Ahsg, Bpgm, and Litaf) and seven downregulated proteins (medium-chain acyl-CoA synthetase 2 (Acsm2), Hadha, Keg1, Sh3glb1, Eif3d, Ambp, and Ddah2). The qPCR technique was used to validate these 10 potential biomarkers in rat kidney and urine. In addition, Acsm2 and Ahsg were double-validated by Western blotting. Overall, this study identified 10 reliable biomarkers that may provide potential targets for the treatment of AKI caused by EHS.

Sensory attributes and functional properties of maillard reaction products derived from the crassosotrea gigas (Ostrea rivularis gould) enzymatic hydrolysate and xylose system.

To improve the flavor of Ostrea rivularis Gould, enzymatic hydrolysis was conducted and xylose-OEH Maillard reaction products were prepared. Then, their physicochemical properties and metabolites were determined by UHPLC-MS-MS, and volatile compounds were determined by GC-MS to investigate the changes. The results showed that His, Gln, Lys, Asp, and Cys were the major amino acids consumed. After being heated at 120 °C for up to 150 min, the DPPH (2,2-Diphenyl-1-picrylhydrazyl) was 85.32 ± 1.35% and the reducing capacity was 1.28 ± 0.12. Both were the highest in the groups. Additionally, 45 volatile compounds, including 2-ethyl-5-methyl-pyrazine and 2-ethyl-3,5-dimethyl-pyrazine, and 678 compounds were identified. We also found that 18 metabolites with significant differences (VIP ≥2) were differential metabolites, which involved lipid oxides and amino acid derivatives. The content of lipids favored the regulation of Maillard products and affected the lower threshold of the flavor of aldehydes, which contributed to the flavor and antioxidant activity. These results suggested the potential of xylose-OEH MRPs as a natural antioxidant for further processing oysters.

Neurotransmitter disturbances caused by methylmercury exposure: Microbiota-gut-brain interaction.

The fetal and early postnatal stages are periods of rapid brain development, during which, methylmercury (MeHg) exposure can cause lasting cognitive impairments. MeHg exposure disrupts neurotransmitter metabolites, which increased susceptibility to neurological responses. However, the neurotoxic mechanism underlying the MeHg-induced disruption of neurotransmitter metabolism requires further exploration. To this end, female Sprague-Dawley (SD) rats were administered NaCl (control group) or MeHg (0.6 mg/kg, 1.2 mg/kg and 2.4 mg/ kg body weight (bw), where the body weight refers to the dams) during the perinatal period, and then changes in neurotransmitter profiles and the gut microbiota of offspring were detected. The results showed that tryptophan (Trp) and tyrosine (Tyr) pathway neurotransmitter metabolites, including serotonin (5-HT), 5-hydroxy indole acetic acid (5-HIAA), N-acetyl-5-hydroxytryptamin (NAS), Tyr, dopamine (DA) and epinephrine (E), were significantly changed, and the Kynurenine/Tryptophan (Kyn/Trp) ratio was increased in the MeHg-treated groups. Meanwhile, acetylcholine (ACh) and neurotransmitters involved in the amino acid pathway were significantly reduced. Notably, MeHg treatment induced a significant reduction in tight junctions in the colon and hippocampal tissue. Furthermore, fecal microbiota analysis indicated that the diversity and composition characteristics were significantly altered by MeHg exposure. Mediation analysis showed that the gut microbiota mediated the effect of MeHg treatment on the neurotransmitter expression profiles. The present findings shed light on the regulatory role of the gut microbiota in MeHg-disrupted neurotransmitter metabolic pathways and the potential impact of perinatal MeHg treatment on the "cross-talk" between the gut and brain.

Impacts of Mercury Exposure Levels and Sources on the Demethylation of Methylmercury Through Human Gut Microbiota.

This study aims to investigate methylmercury (MeHg) demethylation processes in human gut. Here, we determined the compositions and MeHg demethylation rates of gut microbiota in residents from different Hg exposure levels (Wanshan (WS) town and Yangtou (YT) town) and different Hg exposure sources (Zhuchang (ZC) town and YT town) regions. MeHg and inorganic Hg exposure levels in residents of WS town were significantly higher than those of YT and ZC town. Desulfovibrio and Methanogens, which related to Hg methylation/demethylation, showed significantly higher abundance in WS and ZC, comparing with YT. In vitro experiments demonstrated that human intestinal microbiota could degrade MeHg directly. Besides, gut microbiota in WS and ZC exhibited significantly higher demethylation rates than YT, suggesting Desulfovibrio and Methanogens may play important roles in intestinal MeHg demethylation. This study highlights Hg exposure levels and sources may affect demethylation efficiency of gut microbiota, which provides new insights for MeHg demethylation processes in human body.

Sequential posterior interosseous artery perforator flap for reconstruction of dorsal hand defects.

Dorsal hand defects accompanied by exposure of bones and tendons remain a huge challenge for plastic surgeons. The pedicled perforator flaps have unique advantages in resurfacing the defects. This study aimed to investigate the clinical efficacy of the sequential posterior interosseous artery perforator flap for repairing dorsal hand defects. This study was composed of an anatomical study and clinical application. Anatomically, 30 adult upper limb specimens injected with red latex were dissected, the perforators from the branches of the posterior interosseous artery were observed in the dorsal forearm, and the sequential flap based on them was designed based on the anatomical characteristics. Clinically, nine cases of soft tissue defects on the dorsum of the hand were treated by this flap. Anatomically, the posterior interosseous artery divided into an ascending branch and a descending branch, and the descending branch traveled 1.0 ± 0.3 cm down to divide into the ulnar and radial terminal branches. The ulnar terminal branch presented constantly, and the radial terminal branch had an occurrence rate of 93.33%. Clinically, all flaps survived completely and possessed a soft texture and satisfactory appearance, as well as a nonbloated pedicle, and the donor region had a natural color and appearance with only a linear scar left behind. The sequential posterior interosseous artery perforator flap could become a useful option for repairing dorsal hand defects, as it has the advantages of being easy to perform without sacrificing the main vessels and avoiding donor area skin grafting.

New mechanism of nephrotoxicity of triptolide: Oxidative stress promotes cGAS-STING signaling pathway.

Triptolide (TPL) is a bioactive component extracted from the traditional Chinese herb Tripterygium wilfordii Hook F., and has multiple pharmacological activities, such as anti-tumor activity. However, severe adverse effects and toxicity, especially nephrotoxicity, limit its clinical application. It has been demonstrated that mitochondrial defect is a major toxic effects of TPL. In this study, we show that triptolide activated the cGAS-STING signaling pathway in kidney tubular cells in vivo and in vitro. Renal injury models were established in BALB/c mice and human tubular epithelial cells using TPL. We found that TPL enhanced the phosphorylation levels of STING, TBK1 and IRF3, and upregulated the expression of IFNß, which is the production of cGAS-STING signaling pathway. STING inhibitor C176 had protective effects in TPL-induced nephrocyte damage. STING siRNA down regulated the expression level of IFNß. In addition, triptolide induced an increase in protein levels of the transcription factor BACH1, while transcriptional expression of the antioxidant enzyme HMOX1 was reduced due to the increased expression of BACH1. Furthermore, oxidative stress-induced mtDNA damage and DNA leakage caused activation of the cGAS-STING signaling pathway. Altogether, cGAS-STING signaling pathway involved in TPL induced nephrotoxicity. Inhibiting cGAS-STING over-activation may be a new strategy for alleviating renal injury of triptolide.

Highly Selective Carbonylation of CH3 Cl to Acetic Acid Catalyzed by Pyridine-Treated MOR Zeolite.

The selective conversion of methane to high value-added chemicals under mild conditions is of great significance for the commercially viable and sustainable utilization of methane but remains a formidable challenge. Herein, we report a strategy for efficiently converting methane to acetic acid via CH3 Cl as an intermediate. Up to 99.3 % acetic acid and methyl acetate (AA+MA) selectivity was achieved over pyridine-pretreated MOR (MOR-8) under moderate conditions of 523 K and 2.0 MPa. Water, conventionally detrimental to carbonylation reaction over zeolite catalysts, was conducive to the production of AA in the current reaction system. In the 100 h continuous test with the MOR-8 catalyst, the average AA+MA selectivity remained over 98 %. AA was formed by carbonylation of methoxy groups within 8-membered rings of MOR followed by hydrolysis. This strategy provided an approach for highly efficient utilization of methane to oxygenates under mild reaction conditions.

Revealing Potential Diagnostic Gene Biomarkers Associated with Immune Infiltration in Patients with Renal Fibrosis Based on Machine Learning Analysis.

Chronic kidney disease is characterized by the development of renal fibrosis. The basic mechanisms of renal fibrosis have not yet been fully investigated despite significant progress in understanding the etiology of the disease. In this work, the researchers sought to identify potential diagnostic indicators for renal fibrosis. From the GEO database, we were able to acquire two gene expression profiles with publically available data (GSE22459 and GSE76882, respectively) from human renal fibrosis and control samples. 215 renal fibrosis specimens and 124 normal specimens were examined for differentially expressed genes (DEGs). The SVM-RFE and LASSO regression models were used to discover potential markers. CIBERSORT was applied to estimate the combined cohorts' immune cell fraction compositional trends in renal fibrosis. RT-PCR was used to examine the expression of ISG20 in renal fibrosis and healthy samples. In vitro experiments were applied to examine the function of ISG20 knockdown on the progression of renal fibrosis. In this study, we identified 24 DEGs. The result of LASSO and SVM-RFE identified nine critical genes. ROC assays confirmed the diagnostic value of the above nine genes for renal fibrosis. Immune cell infiltration analysis revealed that ISG20 and SERPINA3 were both found to be correlated with T cell follicular helper, neutrophils, T cell CD4 memory activated, eosinophils, T cell CD8, dendritic cell activated, B cell memory, monocytes, macrophage M2, plasma cells, T cell CD4 naïve, mast cell resting, B cell naïve, T cell regulatory, and NK cell activated. Finally, we observed that the expression of ISG20 and SERPINA3 was distinctly increased in renal fibrosis samples compared with normal samples. ISG20 siRNA significantly suppressed the progression of renal fibrosis in vitro. Overall, this study identified nine diagnostic biomarkers for renal fibrosis. ISG20 may be a novel therapeutic target of renal fibrosis.

Effects of Low-dose Mercury Exposure in Newborns on mRNA Expression Profiles.

This study was designed to investigate the molecular mechanism of mercury (Hg) toxicity in the newborns by mRNA sequencing (mRNA-seq). A questionnaire survey, routine blood parameters of pregnant women, and umbilical cord blood (UCB) of newborns were collected. The median (25th percentile, 75th percentile) of total Hg (THg) concentrations in UCB of newborns was 3.63 (2.50, 6.19) µg/L. A total of 504 differentially expressed genes of mRNA were revealed between the case and control group, including 456 upregulated and 48 downregulated genes. The Gene Ontology (GO) analysis showed that differentially expressed genes were primarily involved in mitophagy, hemoglobin complex, and oxygen carrier activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the most differentially expressed genes were annotated in Huntington's disease, Parkinson's disease, and Alzheimer's disease. The qRT-PCR was used to validate the results of mRNA-seq. Low-dose Hg exposure could increase blood NE# and WBC in the pregnant women. This study provides scientific evidences on mechanism of Hg toxicity in newborns.

Coupling of Methanol and Carbon Monoxide over H-ZSM-5 to Form Aromatics.

The conversion of methanol into aromatics over unmodified H-ZSM-5 zeolite is generally not high because the hydrogen transfer reaction results in alkane formation. Now circa 80 % aromatics selectivity for the coupling reaction of methanol and carbon monoxide over H-ZSM-5 is reported. Carbonyl compounds and methyl-2-cyclopenten-1-ones (MCPOs), which were detected in the products and catalysts, respectively, are considered as intermediates. The latter species can be synthesized from the former species and olefins. 13 C isotope tracing and 13 C liquid-state NMR results confirmed that the carbon atoms of CO molecules were incorporated into MCPOs and aromatic rings. A new aromatization mechanism that involves the formation of the above intermediates and co-occurs with a dramatically decreased hydrogen transfer reaction is proposed. A portion of the carbons in CO molecules are incorporated into aromatic, which is of great significance for industrial applications.

Long Non-Coding RNA in Glioma: Target miRNA and Signaling Pathways.

BACKGROUND: Glioma is one of the most common and aggressive malignant tumors of the central nervous system. METHODS: Here, we review and explore the use of long noncoding RNA (lncRNA) as a therapeutic strategy for the targeting of gliomas. RESULTS: LncRNA is a functional RNA molecule with no protein coding function and is involved in the occurrence and progression of glioma. It is reported that the activation of several signaling pathways, including the MAPK, p53, Wnt/ß-catenin, PI3K/AKT/mTOR, and epithelial mesenchymal transformation (EMT) pathways, are involved in the regulation of gliomas. In addition, microRNAs in glioma may also interact with lncRNAs and affect tumor growth and progression. CONCLUSIONS: Therefore, the exploration of lncRNA participation in signaling pathway regulatory mechanisms and the determination of the interaction between lncRNA and miRNA may help to develop new effective therapies for the treatment of glioma.

Two New C19-Diterpenoid Alkaloids from Aconitum nagarum var. lasiandrum.

Continuous investigations of the roots of Aconitum nagarum var. lasiandrum led to the isolation of two new C19-diterpenoid alkaloids, lasiandrine (1) and lasiandroline (2). Their structures were elucidated on the basis of extensive interpretation of spectroscopic and mass spectrometric data.

Exploration of fluorescence-based real-time loop-mediated isothermal amplification (LAMP) assay for detection of Isospora suis oocysts.

Isospora suis is an intestinal protozoan parasite in pigs. The 2-3 weeks old piglets are most often infected by I. suis because their immune system is not fully developed. The infection exhibits clinical features such as diarrhea and dehydration and seriously affects the economic interests of farmers. The traditional method of identifying I. suis relies on the detection of fecal oocysts, which depends heavily on the accumulation of experience. Thus, missed detection, and false alarms often occur during detection. With the development of molecular-based detection methods, development of a simple, convenient and more sensitive method for the detection of I. suis is an urgent need. In this study, based on the 18S rRNA gene sequence, a fluorescence -based real-time loop-mediated isothermal amplification (LAMP) assay was established for the detection of I. suis. The results showed that the assay is highly specific and sensitive, with a detection limit of 2.74 × 10(2) copies/µL recombinant plasmid of I. suis, corresponding to 1 fg/µL plasmid when converted to DNA concentration. The sensitivity is about 100 times higher than conventional PCR. Additionally, DNA extracted from a certain number of oocysts was used for detection, and it showed that the LAMP assay had a detection limit of 5 oocysts, lower than that of 13 oocysts of conventional PCR. The established LAMP assay overcomes the shortage of the traditional microscopy-based method, and provides a valuable way for molecular detection of I. suis.

[Expression, purification and characterization of Rv3194c protein from Mycobacterium tuberculosis].

Objective: PDZ[Post-synaptic density-95 (PSD-95), Drosophilia tumor suppressor protein diskslarge-1 (DLG), the tight junction protein zonula occludentes 1 (ZO-1)] signal protein was encoded by Rv3194c gene from Mycobacterium tuberculosis, and its ability to adhere M. tuberculosis was studied. Methods: Rv3194c protein was expressed in prokaryotic system. Rv3194c protein was separately incubated with hyaluronic acid, chondroitin sulfate and collagen Ι overnight at different temperature (37, 38, 39, 40℃). Then component changes of culture supernatant were tested by Western blot and ELISA. Results: Western blot showed that Rv3194c protein expressed in prokaryotic system, with a molecular weight of about 35 kDa, was mainly in soluble form. Western blot showed that His-Rv3194c protein in supernatant of 39℃ experimental group was significantly less than that of other experimental groups (37, 38, 40℃)(***P<0.001). ELISA showed that hyaluronic acid, chondroitin sulfate and collagen Ι in supernatant of 39℃ experimental group was significantly less than that of other experimental groups (37, 38, 40℃)(***P<0.001). Conclusion: For the first time it was affirmed that Rv3194c protein with detected activity of adhesions in this study will be targeted to the development of the new anti-M. tuberculosis drug.