Untargeted metabonomics and TLR4/ NF-κB signaling pathway analysis reveals potential mechanism of action of Dendrobium huoshanense polysaccharide in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.

Altered N-linked glycosylation in depression: A pre-clinical study.

BACKGROUND: Neuroimmune plays an important role in major depressive disorders (MDD). N-linked protein glycosylation (NLG) might contribute to depression by regulating the neuroinflammatory response. As microglia is the main executor of neuroimmune function in the central neural system (CNS), targeting the process of N-linked protein glycosylation of microglia in the mice used for studying depression might potentially offer new avenues for the strategy for MDD. METHODS: The chronic unpredictable mild stress (CUMS) mouse model was established for the whole brain microglia isolating. Then, RNA samples of microglia were extracted for transcriptome sequencing and mRNA analysis. Immunofluorescence (IF) was used to identify the expression level of NLG-related enzyme, B4galt1, in microglia. RESULTS: The data showed that NLG was positively related to depression. Moreover, the NLG-related gene, B4galt1 increased expression in the microglia of CUMS mice. Then, the inhibition of NLG reversed the depressive behavior in CUMS mice. The expression level of B4galt1 in CUMS mice was upregulating following the NLG-inhibitor treatment. Similar results haven't been observed in neurons. Information obtained from these experiments showed increasing expression of B4galt1 in microglia following depressive-like behaviors. CONCLUSIONS: These findings indicate that NLG in microglia is associated with MDD, and suggest that therapeutically targeting NLG might be an effective strategy for depression. LIMITATIONS: How to modulate the B4galt1 or NLG pathways in microglia efficiently and economically request new technologies.

[Active components and potential mechanism of Taohong Siwu Decoction in regulating ischemic stroke based on target cell trapping combined with network pharmacology, molecular docking, and experimental validation].

The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.

[Origin identification of Poria cocos based on hyperspectral imaging technology].

To realize the non-destructive and rapid origin discrimination of Poria cocos in batches, this study established the P. cocos origin recognition model based on hyperspectral imaging combined with machine learning. P. cocos samples from Anhui, Fujian, Guangxi, Hubei, Hunan, Henan and Yunnan were used as the research objects. Hyperspectral data were collected in the visible and near infrared band(V-band, 410-990 nm) and shortwave infrared band(S-band, 950-2 500 nm). The original spectral data were divided into S-band, V-band and full-band. With the original data(RD) of different bands, multiplicative scatter correction(MSC), standard normal variation(SNV), S-G smoothing(SGS), first derivative(FD), second derivative(SD) and other pretreatments were carried out. Then the data were classified according to three different types of producing areas: province, county and batch. The origin identification model was established by partial least squares discriminant analysis(PLS-DA) and linear support vector machine(LinearSVC). Finally, confusion matrix was employed to evaluate the optimal model, with F1 score as the evaluation standard. The results revealed that the origin identification model established by FD combined with LinearSVC had the highest prediction accuracy in full-band range classified by province, V-band range by county and full-band range by batch, which were 99.28%, 98.55% and 97.45%, respectively, and the overall F1 scores of these three models were 99.16%, 98.59% and 97.58%, respectively, indicating excellent performance of these models. Therefore, hyperspectral imaging combined with LinearSVC can realize the non-destructive, accurate and rapid identification of P. cocos from different producing areas in batches, which is conducive to the directional research and production of P. cocos.

[Origin identification of Polygonatum cyrtonema based on hyperspectral data].

In this study, visual-near infrared(VNIR), short-wave infrared(SWIR), and VNIR + SWIR fusion hyperspectral data of Polygonatum cyrtonema from different geographical origins were collected and preprocessed by first derivative(FD), second derivative(SD), Savitzky-Golay smoothing(S-G), standard normalized variate(SNV), multiplicative scatter correction(MSC), FD+S-G, and SD+S-G. Three algorithms, namely random forest(RF), linear support vector classification(LinearSVC), and partial least squares discriminant analysis(PLS-DA), were used to establish the identification models of P. cyrtonema origin from three spatial scales, i.e., province, county, and township, respectively. Successive projection algorithm(SPA) and competitive adaptive reweighted sampling(CARS) were used to screen the characteristic bands, and the P. cyrtonema origin identification models were established according to the selected characteristic bands. The results showed that(1)after FD preprocessing of VNIR+SWIR fusion hyperspectral data, the accuracy of recognition models established using LinearSVC was the highest, reaching 99.97% and 99.82% in the province origin identification model, 100.00% and 99.46% in the county origin identification model, and 99.62% and 98.39% in the township origin identification model. The accuracy of province, county, and township origin identification models reached more than 98.00%.(2)Among the 26 characteristic bands selected by CARS, after FD pretreatment, the accuracy of origin identification models of different spatial scales was the highest using LinearSVC, reaching 98.59% and 97.05% in the province origin identification model, 97.79% and 94.75% in the county origin identification model, and 90.13% and 87.95% in the township origin identification model. The accuracy of identification models of different spatial scales established by 26 characteristic bands reached more than 87.00%. The results show that hyperspectral imaging technology can realize accurate identification of P. cyrtonema origin from different spatial scales.

Genetic diagnosis of non-classical 21-hydroxylase deficiency by the new nanopore sequencing detection method / 中华检验医学杂志

Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.

Genetic analysis of a rare case with Disorder of sex development due to structural rearrangement of Y chromosome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a rare case with Disorder of sex development.@*METHODS@#Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out.@*RESULTS@#The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223).@*CONCLUSION@#The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.

Role of blood markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection / 中华外科杂志

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2 test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP(35.9±16.2)mg/L,PLT(280.0±104.0)×109/L and CAR 1.3±0.8 in successful group were lower than CRP (71.7±47.3)mg/L,PLT (364.7±119.3)×109/L and CAR 2.5±2.0 in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin (35.3±5.2)g/L and PNI 43.6±6.2 in successful group were higher than ESR/CRP (1.6±1.4),Albumin(31.3±4.8)g/L and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Application of low-depth whole genome sequencing for copy number variation analysis in children with disorders of sex development / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD).@*METHODS@#Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out.@*RESULTS@#Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25].@*CONCLUSION@#CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.

Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.@*METHODS@#Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed.@*RESULTS@#BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05).@*CONCLUSION@#BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.@*UNLABELLED@#The graphical abstract is available on the website www.besjournal.com.

Prenatal diagnosis and pregnancy outcome of fetuses with rare autosomal trisomies indicated by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To analyze the result of prenatal diagnosis and outcome of pregnancy for fetuses with rare autosomal trisomies (RATs) suggested by non-invasive prenatal testing (NIPT).@*METHODS@#A total of 69 608 pregnant women who underwent NIPT at Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were selected as study subjects. The result of prenatal diagnosis and outcome of pregnancy for those with a high risk for RATs were retrospectively analyzed.@*RESULTS@#Among the 69 608 pregnant women, the positive rate of NIPT for high-risk RATs was 0.23% (161/69 608), with trisomy 7 (17.4%, 28/161) and trisomy 8 (12.4%, 20/161) being the most common, and trisomy 17 (0.6%, 1/161) being the rarest. For 98 women who had accepted invasive prenatal diagnosis, 12 fetal chromosomal abnormalities were confirmed, and in 5 cases the results were consistent with those of NIPT, which yielded a positive predictive value of 5.26%. Among the 161 women with a high risk for RATs, 153 (95%) were successfully followed up. 139 fetuses were ultimately born, with only one being clinically abnormal.@*CONCLUSION@#Most women with a high risk for RATs by NIPT have good pregnancy outcomes. Invasive prenatal diagnosis or serial ultrasonography to monitor fetal growth, instead of direct termination of pregnancy, is recommended.

Analysis of a twin pregnancy with false negative result for 22q11.2 deletion syndrome by expanded non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To explore the cause for a twin pregnancy with false negative result for 22q11.2 deletion syndrome by expanded non-invasive prenatal testing (NIPT-plus).@*METHODS@#A pregnant woman with twin pregnancy through in-vitro fertilization and negative result of NIPT-plus was selected as the study subject. Amniocentesis was conducted after ultrasonic finding of fetal abnormalities. In addition to conventional G-banded karyotyping, copy number variation sequencing (CNV-Seq) was used to detect chromosomal microdeletion and microduplication. Clinical data of the woman were analyzed to explore the reasons underlying the false negative result.@*RESULTS@#NIPT-plus has yielded a negative result with 11.77 Mb unique reads and 3.05% fetal fraction. Both fetuses had a normal karyotype (46,XY and 46,XX). CNV-seq indicated that one of the fetuses was normal, whilst the other was diagnosed with a 2.58 Mb deletion in the 22q11.2 region.@*CONCLUSION@#The false negative result may be attributed to the combined influence of low fetal fraction, high BMI, twin pregnancy through IVF and a relatively small deletion fragment. Ultrasonography exam following a low-risk result of NIPT-plus should not be neglected.

Characterization and phylogenetic analysis of complete chloroplast genome of cultivated Qinan agarwood / 中国中药杂志

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.

[Simultaneous determination and pharmacokinetic study of five compounds from total extract of Clinopodium chinense in abnormal uterine bleeding rat plasma by UPLC-MS/MS].

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 µg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C_(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.

Poria cocos polysaccharide prevents alcohol-induced hepatic injury and inflammation by repressing oxidative stress and gut leakiness.

Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.

Rubia cordifolia L. ameliorates DSS-induced ulcerative colitis in mice through dual inhibition of NLRP3 inflammasome and IL-6/JAK2/STAT3 pathways.

The aerial part of â€‹Rubia cordifolia â€‹L. has been used as an herbal medicine for a long time with various pharmacological activities, including anti-inflammatory, anticancer, and antibacterial activities. The most notable usage of these was that this herbal medicine had good therapeutic effects on diarrhea caused by various factors. However, the mechanism for the ethanolic extract of â€‹R. cordifolia â€‹L. (RCEE) to treat Ulcerative colitis (UC) effectively is still unclear. In this study, DSS successfully induced UC mice and then intervene using different polar parts of RCEE. The results indicated that RCEE-treatment inhibited colonic combination NLRP3 inflammasome formation and IL-6/JAK2/STAT3 activation in vivo, significantly ameliorating the clinical symptoms, including alleviating colonic mucosal damage and infiltration of macrophages, suppressing the release of inflammatory cytokines, and reducing mortality. Taken together, this study suggests that dual inhibition of NLRP3 inflammasome and IL-6/JAK2/STAT3 pathways activation using RCEE may be a promising therapeutic strategy for preventing the progression of UC.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Neuroprotective Effect of Taohong Siwu Decoction on Cerebral Ischemia/Reperfusion Injury via Mitophagy-NLRP3 Inflammasome Pathway.

Objective: Globally, cerebral ischemia has been shown to be the second leading cause of death. Our previous studies have shown that Taohong Siwu Decoction (THSWD) exhibits obvious neuroprotective effects on cerebral ischemia/reperfusion (I/R) injury (CIRI). In this study, we further explored the modulatory effect of THSWD on mitochondrial autophagy in CIRI and the relationship between modulatory effect and NLRP3 inflammatory vesicle activation, so as to further explain the mechanism of neuroprotective effect of THSWD. Methods: Middle cerebral artery occlusion reperfusion (MCAO/R) model in rats was built to simulate I/R. Adult male SD rats (220-270 g) were randomly divided into the following four groups: the sham group, the MCAO/R group, the MCAO/R + THSWD group, and the MCAO/R + THSWD + Mitochondrial division inhibitor 1 (Mdivi-1) group. Neurological defect scores were used to evaluate neurological function. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was conducted to measure cerebral infarct volume. Nissl staining, H&E staining and TUNEL staining were executed to detect ischemic cortical neuronal cell viability and apoptosis. Electron microscopy was used to observe the ultrastructural changes of mitochondria. Total Reactive Oxygen Species (ROS) in tissue were measured by fluorescence spectrophotometry, and the activation status of microglia was evaluated by Iba-1/CD16 immunofluorescence staining. The levels of mitophagy-related proteins (LC3, Parkin, PINK1), NLRP3 inflammasome-related proteins (NLRP3, ASC, Pro-caspase-1, Cleaved-caspase-1), and inflammatory cytokines (Pro-IL-18, Pro-IL-1ß, IL-18, IL-1ß) were evaluated by western blotting. Results: The studies showed that THSWD treatment alleviated cerebral infarction and neurological deficiencies. THSWD upregulated the expressions of autophagy markers (LC3-II/LC3-I and Beclin1) mitochondrial autophagy markers (Parkin and PINK1) after CIRI. Furthermore, THSWD treatment attenuated microglia activation and damage to mitochondrial structures, thereby reducing ROS production and NLRP3 inflammasome activation. In contrast, the mitochondrial autophagy inhibitor Mdivi-1 inhibited the above beneficial effects of THSWD. Conclusions: THSWD exhibits neuroprotective effects against MCAO/R in rats by enhancing mitochondrial autophagy and reducing NLRP3 inflammasome activation.