Effects of acetyl groups on the prebiotic properties of glucomannan extracted from Artemisia sphaerocephala Krasch seeds.

This study explores the structural modification of glucomannan extracted from Artemisia sphaerocephala Krasch seeds (60S) to assess the impact of acetyl groups on its prebiotic characteristics. The structural changes were examined, with a focus on the degree of acetyl group substitution (DS). Both deacetylation and acetylation had limited influence on the molecular properties of 60S. Despite these modifications, the apparent viscosity of all samples remained consistently low. In vitro fermentation experiments revealed that Escherichia-Shigella decreased as DS increased, while Bacteroides ovatus was enriched. Acetylation had no significant impact on the utilization rate of 60S but led to a reduction in the production of propionic acid. Furthermore, untargeted metabolomics analysis confirmed the changes in propionic acid levels. Notably, metabolites such as N-acetyl-L-tyrosine, γ-muricholic acid, and taurocholate were upregulated by acetylated derivatives. Overall, acetyl groups are speculated to play a pivotal role in the prebiotic properties of 60S.

Exploring effective implementation pathways to become an excellent chief financial officer in public hospital: a qualitative comparative analysis (QCA) from China.

BACKGROUND: Hospital chief financial officer (CFO) contributes to improving health system performance. However, how to become an excellent hospital CFO has rarely been considered from a holistic perspective. This paper aims to identify competencies required by hospital CFO to fulfil the position's responsibilities and explore effective implementation pathways to generate high performance and improve healthcare service. METHODS: We conducted 61 semi-structured interviews with individuals in key leadership positions in China's hospitals and researchers focusing on healthcare system management to identify core competencies necessary for hospital CFO. Interviews were analysed through a multi-stage review process and modified via expert vetting using a national panel of 23 professors. Subsequently, interviews were conducted with 32 hospital CFOs from 14 provinces throughout September 2021 to May 2022. We scored the performance of 32 hospital CFOs in various aspects of competency and used the fuzzy-set qualitative comparative analysis to explore the competency configurations of excellent CFOs. RESULTS: We identify seven core competencies necessary for a hospital CFO to fulfil management practices, including personal morality, resource management, strategy management, learning ability, negotiating skill, leadership skill, and financial management. The findings indicate that a single competency factor is not a necessary condition to become an excellent hospital CFO. The results of qualitative comparative analysis then make it possible to propose four configurational paths, namely, supportive, interpersonal, all-around development, and technical, to become an excellent hospital CFO and achieve effective managerial performance. CONCLUSIONS: The responsibilities of hospital CFOs are complex and varied, hence, a better understanding of competencies required by CFO is essential to implement their responsibilities effectively. The identification in this study of the four effective implementation pathways to becoming an excellent hospital CFO enriches the literature on hospital management and provides implications for China's hospitals and their CFOs.

Association of probiotic ingestion with serum sex steroid hormones among pre- and postmenopausal women from the NHANES, 2013-2016.

BACKGROUND: Sex hormone-related diseases, encompassing a wide range of conditions from reproductive disorders to certain cancers, pose significant health challenges worldwide. Recent scientific investigations have highlighted the intricate interplay between the gut microbiome and sex hormone regulation, indicating the potential for microbiota-targeted interventions in the management of such diseases. Although individual studies have elucidated the influence of the gut microbiome on sex hormones, a comprehensive cross-sectional examination of the population-wide prevalence of probiotic intake and its correlation with sex hormones is still lacking. OBJECTIVES: This study aimed to evaluate the association of probiotic ingestion with sex hormones in pre- and post-menopausal women. METHODS: We conducted an observational cohort study comprising a nationally representative sample of adults who participated in the National Health and Nutrition Examination Survey between 2013 and 2016. Probiotic ingestion was considered when a subject reported yogurt or probiotic supplement consumption during the 24-h dietary recall or during the Dietary Supplement Use 30-Day questionnaire. A survey-weighted generalized linear model was used to analyze the association between probiotic intake and female/male sex hormones. To reduce selection bias, we used propensity score matching (PSM). RESULTS: This study included 2,699 women, with 537 of them consuming yogurt and/or dietary supplements containing probiotics, while the remaining 2,162 women did not consume any probiotics. The findings indicated that there were associations between probiotic intake and sex hormone levels in premenopausal and postmenopausal women. For premenopausal women, probiotic intake was positively associated with estradiol (E2) levels. On the contrary, in postmenopausal women, probiotic intake was inversely associated with total testosterone (TT) levels. CONCLUSIONS: This study indicated that probiotic consumption was associated with higher E2 level in premenopausal women and lower TT level in postmenopausal women. Probiotic intake might be a sensible strategy for preventing sex hormone-related diseases.

Assessing environmental suitability of Ligusticum chuanxiong based on ecological analyses with chemical and molecular verification.

Ligusticum chuanxiong Hort. as an important Chinese medicinal herb clinically used as anti-inflammatory, antioxidant, and hepatoprotective agents, is widely planted in China. However, related studies on L. chuanxiong's distribution and significant environmental factors that affect its growth are insufficient. Based on climatic, topographic and soil factors, this study predicted current and future distributions of L. chuanxiong and analyzed the distribution transformation under different scenarios. Moreover, the most important environmental factors for modeling were explored using maximum entropy models, chemical analysis and molecular analysis. Results suggested that the predicted distribution of L. chuanxiong was wider than previously reported. Among these environmental variables, climate factors, especially the minimum temperature of the coldest month (Bio6, 46.7%) and solar radiation (SRAD, 43.4%) contributed more than others to L. chuanxiong's distribution with optimum values of 0-1.5 °C and 5000-11,000 kJ/m2 per day. Total and highly suitable areas respectively increased by 26,788-943,820 km2 and 34,757-340,417 km2 in the future (2061-2080, 2081-2100). The distribution centers of suitable zones were predicted to migrate north in the future, and the migration distance was 135.74-479.77 km from current center. Results of chemical content determination suggested that L. chuanxiong should be cultivated in high-suitable places to improve medicinal quality by evaluating contents of ferulic acids and Z-ligustilide. Correlation analysis suggested that both chemical contents and gene expression levels decreased with decreasing habitat suitability, suggesting a strong link between environments, chemical constituents, and gene expression. These findings improve the comprehension of the effects of environments on the distribution patterns of L. chuanxiong, as well the relation between environmental suitability and medicinal quality. These findings provide a useful foundation for the planting, cultivation and conservation of L. chuanxiong.

The alkaloids of Corydalis hendersonii Hemsl. contribute to the cardioprotective effect against ischemic injury in mice by attenuating cardiomyocyte apoptosis via p38 MAPK signaling pathway.

BACKGROUND: There is a characteristic Tibetan folk medicine in China named Corydalis hendersonii Hemsl. (CH) has been used for treatment of cardiovascular related diseases, called "plethora" in Tibetan medicine. Previous studies demonstrated that ethanol extract of CH showed anti-acute myocardial infarction (AMI) effect through inhibiting fibrosis and inflammation. Rich alkaloids fraction (RAF) is isolated from CH, but whether RAF possessing an equivalent effect with the CH ethanol extract and by which mechanism it protects against AMI has not yet reported. The paper aimed to study the potential role of RAF on myocardial injured mice and its underlying mechanism. MATERIALS AND METHODS: Liquid chromatography mass spectrometry-ion trap-time of flight (LCMS-IT-TOF) was used to analyze the chemical profile and isolate pure compounds. The ligation of left anterior descending (LAD) of coronary artery in mice was used to evaluate the in vivo anti-AMI effect, by dividing into eight groups: Sham, Model, Fosinopril (10 mg/kg, i.g.), total extract (TE, 400 mg/kg, i.g.), poor alkaloids fraction  (PAF, 300 mg/kg, i.g.), and RAF (25, 50, and 100 mg/kg, respectively, i.g.) groups. Echocardiography was used to evaluate mice heart function through the index of left ventricular end-systolic  diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), fractional shortening (FS) and ejection fraction (EF). We detected the lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the serum and the plasma level of angiotensin II (AngII). The apoptosis of mice myocardial tissue was verified by TUNEL assay. The expression of p38 mitogen-activated protein kinases (p38 MAPK), Bcl-2 and Bcl-2-associated X protein (Bax) were detected through immunofluorescence staining, qRT-PCR and western blot in mice heart tissue and H9c2 cells. RESULTS: Echocardiography data indicated that the values of LVEDd and LVEDs were reduced and the values of FS and EF were improved by TE and RAF significantly. RAF also decreased the levels of LDH, CK-MB and AngII and significantly inhibited inflammatory cells in the marginal zone of myocardial infarction. The TUNEL assay results showed that RAF significantly attenuated cell apoptosis. Immunofluorescence and qRT-PCR assay showed that RAF inhibited p38 MAPK, Bax, and Bcl-2 proteins in mice myocardium. Western blot results validated that the expressions of key proteins were inhibited by RAF. Also, the apoptotic cells and apoptosis-related proteins were dramatically reduced by RAF in vivo and in vitro. Besides, RAF and PAF were analyzed by LCMS-IT-TOF to identify the main compounds and to demonstrate the difference between them. The results showed that a total of 14 alkaloids were identified, which indicated that the isoquinoline alkaloids were the main ingredients in RAF may contributing to the cardioprotective effect in mice. CONCLUSIONS: RAF improves cardiac function by inhibiting apoptosis via p38 MAPK signaling pathway, and RAF contributes to the effect against myocardial ischemic injury of TE in mice, which provides a substantial reference for the clinical application against ischemia heart disease and quality control of CH.

The traditional Chinese medicine Qiangjing tablet prevents blood-testis barrier injury induced by CdCl2 through the PI3K/Akt/Rictor signaling pathway.

OBJECTIVE: Environmental contaminants such as cadmium (Cd) may have a deleterious impact on sperm and reduce male fertility by compromising the blood-testis barrier (BTB). Hence, the effects of the traditional Chinese medicine Qiangjing tablet (QJP) on sperm quality and BTB alterations induced by Cd in mouse testes were examined. METHODS: Adult KM mice challenged with Cd chloride were examined, QJP was administered to mice as an oral drug by gavage, and the experiments lasted 2 weeks. Testicular and epididymal weights, sperm quality, anti-sperm antibodies (AsAb), hormone levels, and histology were evaluated. Changes in the levels of N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin and their mRNAs were evaluated. The effects of QJP on the PI3K/Akt/Rictor pathway were evaluated. RESULTS: CdCl2 decreased reproductive organ weight, sperm quality, and testosterone (T) levels; increased AsAb, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; induced structural damage in testicles with BTB disruption; increased BTB permeability; and decreased N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin expression. After treatment, QJP blocked the effects of Cd on reproductive organ weight, sperm quality, and T; mitigated germinal epithelium compartment alterations; decreased AsAb, FSH, and LH levels; and preserved BTB ultrastructure and function. In addition, QJP induced increases in N-cadherin, occludin, ZO-1, claudin-11, F-actin, and ß-tubulin levels and the expression of their mRNAs through the PI3K/Akt/Rictor pathway. After the application of JRAB2011, the levels of a specific mTORC2 suppressor, Rictor, and the BTB-protective effect of QJP were greatly reduced. CONCLUSIONS: We demonstrated the effect of QJP against Cd-induced damage to the BTB, and the results indicate that QJP may play a significant role in opposing the effects of Cd through the PI3K/Akt/Rictor pathway.

Diverse lignans with protective effect against hypoxia/oxidative injuries to H9c2 cells from Syringa pinnatifolia Hemsl.

A bioactivity-guided fractionation on the phenolic fractions from the peeled stems of Syringa pinnatifolia Hemsl., one of representative Mongolian folk medicine in China, led to the isolation and structural determination of 11 undescribed lignans and 12 known ones. These lignans cover diverse types, among them syringanones A and B represent an unprecedented carbon skeleton (proposed syringanane) and alashanenol A possesses a rare bicyclo [3.3.1]nonadienemethanol core. Their structures were established by extensive spectroscopic data analysis, X-ray diffraction, and quantum chemical calculations. All isolates were evaluated for their cardioprotective activities on H9c2 cardiomyocytes in vitro. The results showed that five lignans exhibited the protective effects against hypoxia-induced injury at the concentrations of 1.2-40 µM and six lignans exhibited anti-oxidative stress injury at 10-40 µM. These findings account to some extend for the traditional therapeutic effects of S. pinnatifolia for the treatment of ischemic heart diseases in clinic.

Zerumbone, a major sesquiterpene from Syringa pinnatifolia Hemsl., exerts the sedative effect by regulating GABAergic nervous system.

ETHNOPHARMACOLOGICAL RELEVANCE: Zerumbone (ZER) is a humulane sesquiterpenoid isolated from Syringa pinnatifolia Hemsl. (SP), its content accounts for 64.7% of volatile oil and 0.86% of total ethanol extract (TEE), representing one of characteristic ingredient of SP. As a representative Mongolian medicine with anti-"Khii", anti-asthma, and clearing-heat effects, SP has been used for the treatment of cardiovascular diseases, upset, insomnia, and other symptoms. AIM OF STUDY: Previous results showed that TEE has sedative effect, but the pharmacological substances and its sedative mechanism remains unclear. This study aims to determine whether ZER, as one of major and characteristic sesquiterpenoids of SP, contributes to the sedative effect of SP and its underlying mechanism. MATERIALS AND METHODS: Locomotor activity and threshold dose of pentobarbital sodium sleep experiments were used to evaluate the sedative effects in mice. ELISA assay was used to examine the level of GABA/Glu ratio in rats hippocampus, cortex and hypothalamus tissue. The binding ability of ZER with glutamic acid decarboxylase 67 (GAD67) and Gephyrin protein were predicted by molecular docking. Western blot and Immunohistochemistry assay were used to determine the expression of GABAergic nerve system related proteins (GAD67, Gephyrin) in rat's hypothalamus. ZER was co-administrated with flumazenil and bicuculline (GABAA antagonist) to determine whether it acts on GABAA receptor. Furthermore, MQAE assay was used to test the effect of ZER on the chloride ion concentration in cerebellar granule cells. RESULTS: Current data demonstrated that ZER dose-dependently (5-20 mg/kg) reduces the locomotor activity and sleep latency of mice, and extend sleeping time of mice. The results of ELISA showed that ZER increases the level of GABA/Glu in rats brain tissue, in particular in hypothalamus. Molecular docking results revealed that ZER has a strong affinity to GAD67 and Gephyrin protein. The Western blot and Immunohistochemistry data indicated that ZER up-regulates the expression of GAD67 and Gephyrin protein in rat's hypothalamus. Antagonism test results demonstrated that flumazenil and bicuculline reverse the effect of ZER on threshold dose of pentobarbital sodium sleep experiments. In addition, ZER also could dose-dependently (5-20 µM) increase the chloride ion concentration in cerebellar granule cell, suggesting that ZER induces the opening of chloride channel, exerts central inhibitory effect. CONCLUSION: ZER has a significant sedative effect in mice and rat, and the effect is associated with GABAergic nervous system. The present results suggest that ZER, as one of the major bioactive ingredients of SP, contributes to the sedative effect and provide substantial evidence for its traditional use of anti-"Khii" in clinic of Syringa pinnatifolia.

Potential role of selenium in alleviating obesity-related iron dyshomeostasis.

Obesity is a serious health problem in modern life and increases the risk of many comorbidities including iron dyshomeostasis. In contrast to malnourished anemia, obesity-related iron dyshomeostasis is mainly caused by excessive fat accumulation, inflammation, and disordered gut microbiota. In obesity, iron dyshomeostasis also induces disorders associated with gut microbiota, neurodegenerative injury, oxidative damage, and fat accumulation in the liver. Selenium deficiency is often accompanied by obesity or iron deficiency, and selenium supplementation has been shown to alleviate obesity and overcome iron deficiency. Selenium inhibits fat accumulation and exhibits anti-inflammatory activity. It regulates gut microbiota, prevents neurodegenerative injury, alleviates oxidative damage to the body, and ameliorates hepatic fat accumulation. These effects theoretically meet the requirements for the inhibition of factors underlying obesity-related iron dyshomeostasis. Selenium supplementation may have a potential role in the alleviation of obesity-related iron dyshomeostasis. This review verifies this hypothesis in theory. All the currently reported causes and results of obesity-related iron dyshomeostasis are reviewed comprehensively, together with the effects of selenium. The challenges and strategies of selenium supplementation are also discussed. The findings demonstrate the possibility of selenium-containing drugs or functional foods in alleviating obesity-related iron dyshomeostasis.

Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway.

BACKGROUND: The blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats. METHODS: BTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues. RESULTS: QJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB. CONCLUSION: These results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

Zerumbone, a humulane sesquiterpene from Syringa pinnatifolia, attenuates cardiac fibrosis by inhibiting of the TGF-ß1/Smad signaling pathway after myocardial infarction in mice.

BACKGROUND: Zerumbone (ZER) is a humulane sesquiterpene isolated from Syringa pinnatifolia Hemsl., a representative Mongolian herbal medicine that is used to treat cardiovascular diseases. Cardiac fibrosis is a common pathological process in cardiovascular disease that results from the excessive accumulation of extracellular matrix (ECM), and the transforming growth factor (TGF)-ß/Smad pathway is a canonical signaling pathway that directly induces expressions of ECM-related genes. Currently, the cardioprotective effect and underlying mechanisms of ZER on the inhibition of cardiac fibrosis are not well known. PURPOSE: To explore the cardioprotective properties and pharmacological mechanism of ZER against cardiac fibrosis via the TGF-ß1/Smad signaling pathway. METHODS: Myocardial infarction (MI) model was induced by ligation of the left anterior descending coronary artery in ICR mice. The mice were randomly divided into six groups: sham, model, low-dose ZER (ZER-L), medium-dose ZER (ZER-M), high-dose ZER (ZER-H) and fosinopril. Mice in each group were intragastrically administered treatments for 21 days, and cardiac function was evaluated by 2D echocardiography. The pathological structure of the heart was examined by hematoxylin and eosin (HE) and Masson staining. Content of collagen I and collagen III were assessed by immunofluorescence methods. The inhibitory effect of ZER on TGF-ß1 protein expression was predicted by molecular docking technology. Reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting were used to measure the levels of genes and proteins expressed in the TGF-ß1/Smad signaling pathway and MMPs. TGF-ß1-treated cardiac fibroblasts (CFs) of neonatal SD rats were adopted for in vitro studies. RESULTS: Cardiac ejection fraction (EF) and fractional shortening (FS) in the model group were markedly decreased compared with those in the sham group, indicating that the MI model was successfully established. ZER and fosinopril elevated EF and FS values, suggesting cardioprotective effects. Pathological staining and immunofluorescence analysis showed that the content of collagen I and collagen III increased in the cardiac tissue of mice in model group, while ZER treatment obviously reduced collagen levels. The molecular docking simulations predicted the hydrophobic interactions between ZER and TGF-ß1. In addition, the expression of TGF-ß1, p-Smad2/3 and MMPs in the ZER treatment group was significantly decreased compared with the model group. In vitro studies further confirmed that α-smooth muscle actin (α-SMA) and p-Smad2/3 increased markedly in cardiac fibroblasts after incubation with TGF-ß1, and treatment with ZER suppressed the expression of α-SMA and TGF-ß1 downstream proteins in cardiac fibroblasts. CONCLUSION: ZER rescues cardiac function by attenuating cardiac fibrosis, and the antifibrotic effect may be mediated by blocking the TGF-ß1/Smad pathway.

Qishen granule (QSG) exerts cardioprotective effects by inhibiting NLRP3 inflammasome and pyroptosis in myocardial infarction rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishen granule (QSG) is a traditional Chinese medicine formulation that is widely used in clinical practice for the treatment of myocardial infarction (MI), and its efficacy and safety have been well approved. However, the underlying mechanism by which QSG alleviates inflammation and cell pyroptosis remains unknown. AIM OF THE STUDY: The aim of this study was to clarify whether QSG ameliorated MI by inhibiting inflammasome activation and cell pyroptosis. MATERIALS AND METHODS: In vivo, SD male rats were subjected to the left anterior ascending branch (LAD) ligation to construct MI model. And in vitro, OGD/R, ISO, Ang II and LPS-ATP were used to induce H9C2 cell injury. Cell viability and ROS were detected by CCK8 and DCFH-DA dye respectively. Western blots were applied to detect the expression of inflammasome-related proteins. Cell pyroptosis was evaluated by Calcein-AM/PI staining, Hoechst/PI staining and NT-GSDMD expression. RESULTS: QSG administration improved the cardiac function, as well as reduced inflammatory cell infiltration and collagen deposition. In H9C2 cells, OGD/R failed to induce inflammasome activation, while ISO, Ang II and LPS-ATP successfully induced inflammasome activation and cell pyroptosis, as evidenced by increased Caspase-1(P20) and NT-GSDMD. In LPS-ATP induced H9C2 model, ROS production and cell pyroptosis were suppressed when treated with QSG. Furthermore, QSG significantly decreased the protein levels of P65-NF-κB, NLRP3, ASC, Caspase-1 (P20), Cleaved IL-18, Cleaved IL-1ß and NT-GSDMD. CONCLUSION: This study is the first to demonstrate that QSG has cardioprotective effects by inhibiting inflammasome activation and pyroptosis, which are considered as promising therapeutic targets for MI.

Vitamin A supplementation ameliorates ulcerative colitis in gut microbiota-dependent manner.

Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.

[Research progress on in vitro models of cardiomyocyte injury].

Cardiovascular diseases seriously endanger human health and life. The accompanying myocardial injury has been a focus of attention in society. Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics. In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism. Therefore,the selection and establishment of in vitro model are crucial for the in-depth research. This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity. Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.

A review of nardosinone for pharmacological activities.

Nardostachys jatamansi is a natural medicinal plant that is widely used in Asia for the treatment of various neurological and cardiac diseases, and nardosinone is the main active ingredient of N. jatamansi, which has the potential to treat a variety of diseases. Herein, we summarize the reported chemical structure, pharmacokinetics and pharmacological potential of nardosinone, and point out areas for further research. We obtained studies that were related to the chemical structure and pharmacological activities of nardosinone from several databases. Previous studies have shown that nardosinone has anti-inflammatory effects, anti-hypertrophic effect in cardiomyocytes, enhances activity of the nerve growth factor and promotes neural stem cells to proliferate and differentiate. However, the molecular mechanism of how nardosinone promotes proliferation and differentiation of neural stem cells, and its role in resisting cardiomyocyte hypertrophy remains unclear and needs to be further studied. Overall, nardosinone has the potential to treat bacterial infections, periodontitis, cardiac diseases, neurodegenerative diseases and cancer. However, the gaps found in the literature is the lack of more comprehensive information regarding the pharmacokinetics and toxicology of nardosinone.

[Effect of total phenolic part of Rhus chinensis against myocardial ischemia in mice].

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.

The anti-obesity effects exerted by different fractions of Artemisia sphaerocephala Krasch polysaccharide in diet-induced obese mice.

Artemisia sphaerocephala Krasch polysaccharide (ASKP) consists of two main fractions, 60P (molecular weight at 551 kDa) and 60S (molecular weight at 39 kDa). The anti-obesity effects of ASKP and its two fractions were investigated in high-fat-diet-fed mice and showed similar capability in efficiently preventing the development of obesity. The final body weight and body weight gain of obesity mice model were reduced by 12.44% and 35.33% by ASKP, 10.63% and 34.35% by 60P, and 7.82% and 20.04% by 60S. They also showed similar efficiency to ameliorate dyslipidemia, systematic inflammation, and gut dysbiosis. The colonic genes of barrier integrity were significantly upregulated and the genes of hepatic lipid metabolism and that of colonic inflammatory response were suppressed. They attenuated the gut dysbiosis in obese mice, such as the significant enrichment of beneficial genera (Bifidobacterium and Olsenella) and suppression of harmful ones (Mucispirillum and Helicobacter). Significant enrichment of carbohydrate metabolism associated with the promotion of short-chain fatty acid production and decrease of the metabolisms related to obesity and gut dysbiosis (valine, leucine, and isoleucine biosynthesis, and nitrogen metabolism) were also observed by the administration of ASKP, 60P, and 60S. Overall, these polysaccharides showed potential in acting as prebiotics in preventing high-fat-diet-induced obesity.

Genome-wide analyses of tandem repeats and transposable elements in patchouli.

Patchouli, Pogostemon cablin (Blanco) Benth., is a traditional Chinese medicinal plant from the order Lamiales. It is considered a valuable herb due to its essential oil content and range of therapeutic effects. This study aimed to explore the evolutionary history of repetitive sequences in the patchouli genome by analyzing tandem repeats and transposable elements (TEs). We first retrieved genomic data for patchouli and four other Lamiales species from the GenBank database. Next, the content of tandem repeats with different period sizes was identified. Long terminal repeats (LTRs) were then identified with LTR_STRUC. Finally, the evolutionary landscape of TEs was explored using an in-house PERL program. The analysis of repetitive sequences revealed that tandem repeats constitute a higher proportion of the patchouli genome compared to the four other species. Analyses of TE families showed that most of the repetitive sequences in the patchouli genome are TEs, and that recently inserted TEs make up a comparatively larger proportion than older ones. Our analyses of LTR retrotransposons in their host genome indicated the existence of ancient LTR retrotransposon expansion, and the escape of these elements from natural selection revealed their ages. Our identification and analyses of repetitive sequences should provide new insights for further investigation of patchouli evolution.

hiPSC-Derived Cardiac Tissue for Disease Modeling and Drug Discovery.

Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.

Multifunctional epiberberine mediates multi-therapeutic effects.

Epiberberine, a natural protoberberine from Coptis chinensis Franch., is a potential alkaloid for the treatment of a variety of chronic diseases. The aim of this study is to summarize recent advances in the multiple and potential therapeutic effects of epiberberine. High-quality researches published in last two decades were retrieved from Web of science, ScienceDirect, PubMed and Springer with keywords namely 'epiberberine', 'protoberberine', 'coptis', 'huanglian', 'Coptidis rhizoma' and vital targets of some pathways in anti-adipogenesis, anti-dyslipidemia and anti-cancer activities. All the available research studies indicated that epiberberine is a multi-target small molecule with a low toxicity and exerts many activities including anti-adipogenesis via Akt and ERK pathways, anti-dyslipidemia via inhibition on cholesterol synthesis, anti-cancer via p53/Bax apoptosis pathway, anti-bacterial, improvement in diabetes and Alzheimer's disease. The present work will shed light on the direction for future investigations. Undoubtedly, C. chinensis and epiberberine are expected to exert beneficial effects in various diseases. However, there is a lack of evaluation of clinical applications and underlying molecular mechanisms of epiberberine in diabetes and dementia.