Objective To investigate the effects of Bushen Shengjing Tiaohe Qixue Prescription on rats with diminished ovarian reserve(DOR)based on Wnt/β-catenin signaling pathway.Methods Totally 60 8-week-old SD female rats were randomly divided into control group,model group,estradiol valerate group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the control group,the rats in the other groups were given a single intraperitoneal injection of cyclophosphamide 75 mg/kg to replicate the DOR rat model.From the next day of modeling,the corresponding drugs was administered for medication groups by gavage for 3 weeks.The general conditions of the rats were observed,ELISA was used to detect the contents of serum follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),anti-mullerian hormone(AMH)and inhibin B(INHB),HE staining was used to observe the morphologic changes in ovarian tissue,Western blot was used to detect GSK3β,β-catenin,CyclinD1 and c-MYC protein expressions in ovarian tissues,immunohistochemical staining was used to observe β-catenin expression in ovarian tissue,RT-qPCR was used to detect Wnt1,Wnt2,Wnt4,GSK3β,β-catenin,CyclinD1 and c-MYC mRNA expression in ovarian tissue,transmission electron microscopy was used to observe ultrapathologic structure of ovarian granulosa cells.Results Compared with the control group,the rats in the model group had reduced intake of food and water,slow or even reduced body mass gain,and disturbed estrous cycle,the serum contents of FSH and LH increased(P<0.01),the contents of E2,AMH and INHB decreased(P<0.01);the number of follicles of all levels in ovarian tissue was reduced,and there was increased number of atretic follicles with disturbed arrangement of the granulosa cells;the expression of GSK3β protein in ovarian tissue increased(P<0.01),the expression of β-catenin,CyclinD1 and c-MYC protein decreased(P<0.05,P<0.01),and β-catenin positive expression decreased(P<0.01),the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue decreased(P<0.01),GSK3β mRNA expression was increased(P<0,01);organelles such as mitochondria and nuclei of ovarian granulosa cells were highly swollen and partially lysed.Compared with the model group,the rats in the administered group all had different degrees of body mass increase,partial restoration of the motility cycle,serum FSH and LH contents decreased,and serum E2,AMH and INHB contents increased(P<0.01,P<0.05);the number of follicles at all levels in ovarian tissue increased to varying degrees,and the atretic follicles were reduced;the expression of GSK3β protein in ovarian tissue decreased,β-catenin,CyclinD1 and c-MYC protein expressions increased,β-catenin positive expression increased,the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue increased,and GSK3β mRNA expression decreased,with statistical significance in estradiol valerate group and TCM high-dosage group(P<0.05,P<0.01);mitochondria,endoplasmic reticulum and other organelles of ovarian granulosa cells were mildly to moderately swollen.Conclusion Bushen Shengjing Tiaohe Qixue Prescription can improve ovarian function and regulate serum sex hormone levels in DOR model rats,and its mechanism might be related to the activation of Wnt/β-catenin signaling pathway.

Excessive fat accumulation,viral infections and sustained inflammatory responses caused by non-alcoholic and alcoholic factors can contribute to liver inflammation,fibrosis and carcinogenesis,promoting the development of chronic liver disease.Gaining an in-depth understanding of the etiologic factors and underlying mechanisms that lead to chronic liver disease can help identify potential therapeutic targets for targeted therapy.Lactate,as an important substance in hepatic metabolism,has been found to be involved in the process of chronic liver disease through various pathways,and this review will provide a useful reference for the prevention and treatment of chronic liver disease.

Objective To investigate the effects of Bushen Shengjing Tiaohe Qixue Prescription on rats with diminished ovarian reserve(DOR)based on Wnt/β-catenin signaling pathway.Methods Totally 60 8-week-old SD female rats were randomly divided into control group,model group,estradiol valerate group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the control group,the rats in the other groups were given a single intraperitoneal injection of cyclophosphamide 75 mg/kg to replicate the DOR rat model.From the next day of modeling,the corresponding drugs was administered for medication groups by gavage for 3 weeks.The general conditions of the rats were observed,ELISA was used to detect the contents of serum follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),anti-mullerian hormone(AMH)and inhibin B(INHB),HE staining was used to observe the morphologic changes in ovarian tissue,Western blot was used to detect GSK3β,β-catenin,CyclinD1 and c-MYC protein expressions in ovarian tissues,immunohistochemical staining was used to observe β-catenin expression in ovarian tissue,RT-qPCR was used to detect Wnt1,Wnt2,Wnt4,GSK3β,β-catenin,CyclinD1 and c-MYC mRNA expression in ovarian tissue,transmission electron microscopy was used to observe ultrapathologic structure of ovarian granulosa cells.Results Compared with the control group,the rats in the model group had reduced intake of food and water,slow or even reduced body mass gain,and disturbed estrous cycle,the serum contents of FSH and LH increased(P<0.01),the contents of E2,AMH and INHB decreased(P<0.01);the number of follicles of all levels in ovarian tissue was reduced,and there was increased number of atretic follicles with disturbed arrangement of the granulosa cells;the expression of GSK3β protein in ovarian tissue increased(P<0.01),the expression of β-catenin,CyclinD1 and c-MYC protein decreased(P<0.05,P<0.01),and β-catenin positive expression decreased(P<0.01),the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue decreased(P<0.01),GSK3β mRNA expression was increased(P<0,01);organelles such as mitochondria and nuclei of ovarian granulosa cells were highly swollen and partially lysed.Compared with the model group,the rats in the administered group all had different degrees of body mass increase,partial restoration of the motility cycle,serum FSH and LH contents decreased,and serum E2,AMH and INHB contents increased(P<0.01,P<0.05);the number of follicles at all levels in ovarian tissue increased to varying degrees,and the atretic follicles were reduced;the expression of GSK3β protein in ovarian tissue decreased,β-catenin,CyclinD1 and c-MYC protein expressions increased,β-catenin positive expression increased,the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue increased,and GSK3β mRNA expression decreased,with statistical significance in estradiol valerate group and TCM high-dosage group(P<0.05,P<0.01);mitochondria,endoplasmic reticulum and other organelles of ovarian granulosa cells were mildly to moderately swollen.Conclusion Bushen Shengjing Tiaohe Qixue Prescription can improve ovarian function and regulate serum sex hormone levels in DOR model rats,and its mechanism might be related to the activation of Wnt/β-catenin signaling pathway.

Excessive fat accumulation,viral infections and sustained inflammatory responses caused by non-alcoholic and alcoholic factors can contribute to liver inflammation,fibrosis and carcinogenesis,promoting the development of chronic liver disease.Gaining an in-depth understanding of the etiologic factors and underlying mechanisms that lead to chronic liver disease can help identify potential therapeutic targets for targeted therapy.Lactate,as an important substance in hepatic metabolism,has been found to be involved in the process of chronic liver disease through various pathways,and this review will provide a useful reference for the prevention and treatment of chronic liver disease.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Objective To establish the GC characteristic choromatogram of Huanglian Shangqing tablets(pills and granules),and to investigate the quality of the medicinal materials(Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae)containing volatile oil in Huanglian Shangqing tablets(pills and granules).Methods Agilient HP-5 capillary column(30 m×0.32 mm,0.25 μm)was used with temperature programming,the split ratio was 5∶1,the split flow was 5 mL·min-1,the injection volume was 1 μL,and the inlet temperature was 250℃.A hydrogen flame ionization detector was used,with the detector temperature of 260℃,and the column flow was 1 mL·min-1.The quality of samples from different manufacturers was evaluated by using the GC characteristic choromatogram of volatile oil and the identification of characteristic peaks,combined with similarity analysis and principal component analysis.Results The characteristic chromatograms of 192 batches of samples from 56 manufacturers were established.The peaks of Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae were identified as α-pinene and β-pinene,menthol and menthone,and pulegone respectively.The GC choromatogram of volatile oil components in Huanglian Shangqing tablets(pills)from different manufacturers were quite different,and some peaks of indicator components in the products from a few manufacturers have missing.Conclusion The established GC characteristic chromatograms can reflect the product quality status and can be used for the quality evaluation and product quality control of Huanglian Shangqing tablets(pills and capsules).Huanglian Shangqing tablets(pills and capsules)from some manufacturers are insufficient in the active ingredients of volatile oil,therefore,the product quality needs to be improved.

Farnesoid X receptor (FXR) is a nuclear receptor activated by bile acid that is involved in regulating gene expression related to bile acid, fat, glucose, and amino acid metabolism. The activity of FXR is regulated by a variety of post-translational modifications. Common post-translational modifications of FXR include O-GlcNAcylation, phosphorylation, acetylation, sumoylation, methylation, etc. These post-translational modifications may affect FXR binding of DNA and ligand, heterodimerization, and subcellular localization, and may specifically regulate downstream gene transcription and expression. Different post-translational modifications can lead to changes in FXR stability and biological function, which are closely related to the occurrence of diseases. This paper aims to review the post-translational modification of FXR in the past five years and the mechanisms involved in disease regulation, to explore the effects of post-translational modification on the physiological function of FXR and to provide a theoretical basis for mechanism research targeting FXR.

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.
Animals ; Zebrafish ; Rhus/chemistry* ; Triterpenes/analysis* ; Coronary Disease ; Thrombosis

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.
Infant, Newborn ; Humans ; Pregnancy ; Female ; Scutellaria baicalensis ; Premature Birth/drug therapy* ; Flavonoids ; Plant Extracts/pharmacology* ; Medicine, Chinese Traditional ; Ethnopharmacology ; China

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.