Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.

Comparative efficacy of Chinese herbal injections in patients with cardiogenic shock (CS): a systematic review and Bayesian network meta-analysis of randomized controlled trials.

Background: Cardiogenic shock (CS) is the primary cause of death in patients suffering acute myocardial infarction. As an emerging and efficacious therapeutic approach, Chinese herbal injections (CHIs) are gaining significant popularity in China. However, the optimal CHIs for treating CS remain uncertain. Method: We searched eight databases from inception to 30 September 2023. Subsequently, we conducted the Bayesian network meta-analysis (NMA). Interventions were ranked based on the surface under the cumulative ranking curve (SUCRA) probability values. To compare the effects of CHIs on two distinct outcomes, a clustering analysis was performed. Furthermore, the quality of the studies was assessed. Results: For the study, we included 43 RCTs, encompassing 2,707 participants. The study evaluated six herbal injections, namely, Shenfu injection (SF), Shengmai injection (SM), Shenmai injection (Sm), Danshen injection (DS), Huangqi injection (HQ), and Xinmailong injection (XML). The analysis findings suggested that Sm (MD = -1.05, 95% CI: -2.10, -0.09) and SF (MD = -0.81, 95% CI: -1.40, -0.25) showed better efficacy compared to Western medicine (WM) alone in reducing in-hospital mortality. The SUCRA values revealed that Sm + WM ranked first in terms of in-hospital mortality, cardiac index (CI), and hourly urine output but second in improving left ventricular ejection fraction (LVEF) and mean arterial pressure (MAP). SF + WM, however, had the greatest impact on raising the clinical effective rate. In MAP, SM + WM came out on top. Moreover, in terms of safety, only 14 studies (31.8%), including five types of CHIs: SF, Sm, SM, HQ, and XML, observed adverse drug reactions. Conclusion: To summarize, this analysis discovered that, in terms of patients suffering from CS, CHIs + WM yielded significantly greater advantages than WM alone. Based on in-hospital mortality and the remaining outcomes, Sm performed excellently among all the involved CHIs. Systematic Review Registration: https:// www.Crd.york.ac.uk/prospero/, identifier: CRD42022347053.

A novel network pharmacology strategy to decode mechanism of Wuling Powder in treating liver cirrhosis.

BACKGROUND: Liver cirrhosis is a chronic liver disease with hepatocyte necrosis and lesion. As one of the TCM formulas Wuling Powder (WLP) is widely used in the treatment of liver cirrhosis. However, it's key functional components and action mechanism still remain unclear. We attempted to explore the Key Group of Effective Components (KGEC) of WLP in the treatment of Liver cirrhosis through integrative pharmacology combined with experiments. METHODS: The components and potential target genes of WLP were extracted from published databases. A novel node importance calculation model considering both node control force and node bridging force is designed to construct the Function Response Space (FRS) and obtain key effector proteins. The genetic knapsack algorithm was employed to select KGEC. The effectiveness and reliability of KGEC were evaluated at the functional level by using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the effectiveness and potential mechanism of KGEC were confirmed by CCK-8, qPCR and Western blot. RESULTS: 940 effective proteins were obtained in FRS. KEGG pathways and GO terms enrichments analysis suggested that effective proteins well reflect liver cirrhosis characteristics at the functional level. 29 components of WLP were defined as KGEC, which covered 100% of the targets of the effective proteins. Additionally, the pathways enriched for the KGEC targets accounted for 83.33% of the shared genes between the targets and the pathogenic genes enrichment pathways. Three components scopoletin, caryophyllene oxide, and hydroxyzinamic acid from KGEC were selected for in vivo verification. The qPCR results demonstrated that all three components significantly reduced the mRNA levels of COL1A1 in TGF-ß1-induced liver cirrhosis model. Furthermore, the Western blot assay indicated that these components acted synergistically to target the NF-κB, AMPK/p38, cAMP, and PI3K/AKT pathways, thus inhibiting the progression of liver cirrhosis. CONCLUSION: In summary, we have developed a new model that reveals the key components and potential mechanisms of WLP for the treatment of liver cirrhosis. This model provides a reference for the secondary development of WLP and offers a methodological strategy for studying TCM formulas.

Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

Effect of the staging comprehensive treatment with acupuncture-moxibustion on Bell's facial palsy in the acute stage. / 针灸分期综合治疗急性期贝尔面瘫疗效观察.

OBJECTIVES: To compare the clinical effect on Bell's facial palsy in the acute stage between the staging comprehensive treatment with acupuncture-moxibustion and western medication. METHODS: Sixty patients with Bell's facial palsy in the acute stage were randomly divided into an observation group and a control group, with 30 cases in each one. The patients in the control group were administered orally with prednisone acetate tablets and methylcobalamin tablets until the 28th day of illness. In the observation group, the staging comprehensive treatment with acupuncture-moxibustion was adopted. On the affected side, Qianzheng (EX-HN 16), Yifeng (TE 17), Sibai (ST 2), Yangbai (GB 14), Jiache (ST 6), Dicang (ST 4) and Touwei (ST 8), etc. were stimulated. In the acute stage (Day 1 to 7 of illness), the routine acupuncture and the point-toward-point needle insertion were delivered, no any manipulation was exerted at acupoints, and the needles were retained for 30 min. In the subacute stage (Day 8 to 14 of illness), on the base of the treatment as the acute stage, the depth of needle insertion was adjusted at a part of acupoints and the even needling technique was operated by twisting needle. Besides, electroacupuncture (EA) was attached to Qianzheng (EX-HN 16) and Dicang (ST 4), with continuous wave of low intensity and high frequency, 100 Hz, for 20 min. In the recovery stage (Day 15 to 28 of illness), on the base of the treatment as the subacute stage, the heavy stimulation of acupuncture was given, in which, the sticking and lifting needle techniques were delivered after the needles were inserted from Sibai (ST 2) toward Dicang (ST 4), and from Dicang (ST 4) toward Jiache (ST 6), separately; warm needling was operated at Yifeng (TE 17), and EA changed to stimulate the acupoints with the intermittent wave of high intensity and low frequency, 2 Hz, for 30 min. Acupuncture-moxibustion was given once every other day until the end of the 28th day of illness. The level of House-Brackmann facial nerve function rating scale (H-B grade),the score of Sunnybrook facial nerve grading system (Sunnybrook), the score of facial disability index (FDI), the temperature difference in the infrared thermal imaging facial area and electromyogram (EMG) situation of the affected muscle group were observed before and after treatment in the two groups. Using musculoskeletal ultrasound,the facial nerve diameter was detected and the clinical effect was compared between the two groups. RESULTS: After treatment, the level of H-B grade, Sunnybrook score, the scores of physical function and social life function in FDI were improved when compared with those before treatment in the patients of either group (P<0.01, P<0.05), and the results of these evaluations in the observation group were better than those of the control group (P<0.05). After treatment, the temperature difference of the frontal area, the eye area, the zygomatic area and the mouth corner was declined in comparison with that before treatment in the two groups (P<0.05), and the temperature difference in each area in the observation group was lower than that of the control group (P<0.05).The root mean square (RMS) of the frontal muscle group, the zygomatic muscle group and the orbicularis muscle group on the affected side increased in comparison with that before treatment in the two groups (P<0.01), and RMS of the observation group was higher than that of the control group (P<0.05) after treatment. Before treatment, the diameter of the facial nerve on the affected side was larger than that on the healthy side (P<0.01), and after treatment, the diameter on the affected side was reduced when compared with that before treatment in the two groups (P<0.01); the diameter of the facial nerve on the affected side in the observation group was smaller than that of the control group (P<0.05), while, the diameter on the affected side was larger when compared with the healthy side in the control group (P<0.05). The total effective rate of the observation group was 93.3% (28/30), higher than that of the control group (83.3% [25/30], P<0.05). CONCLUSIONS: The staging comprehensive treatment with acupuncture-moxibustion is clearly effective on Bell's facial palsy in the acute stage, which affirms the effectiveness of acupuncture-moxibustion for the acute stage of Bell's facial palsy in comparison with conventional western medication.

The ROS/SIRT1/STAR axis as a target for melatonin ameliorating atrazine-induced mitochondrial dysfunction and steroid disorders in granulosa cells.

The granulosa cells (GCs) of birds are essential for the reproduction and maintenance of populations in nature. Atrazine (ATR) is a potent endocrine disruptor that can interfere with reproductive function in females and Diaminochlorotriazine (DACT) is the primary metabolite of ATR in the organism. Melatonin (MT) is an endogenous hormone with antioxidant properties that plays a crucial role in development of animal germ cells. However, how ATR causes mitochondrial dysfunction, abnormal secretion of steroid hormones, and whether MT prevents ATR-induced female reproductive toxicity remains unclear. Thus, the purpose of this study is to investigate the protective effect of MT against ATR-induced female reproduction. In the present study, the GCs of quail were divided into 6 groups, as follows: C (Serum-free medium), MT (10 µM MT), A250 (250 µM ATR), MA250 (10 µM MT+250 µM ATR), D200 (200 µM DACT) and MD200 (10 µM MT+200 µM DACT), and were cultured for 24 h. The results revealed that ATR prevented GCs proliferation and decreased cell differentiation. ATR caused oxidative damage and mitochondrial dysfunction, leading to disruption of steroid synthesis, which posed a severe risk to GC's function. However, MT supplements reversed these changes. Mechanistically, our study exhibited that the ROS/SIRT1/STAR axis as a target for MT to ameliorate ATR-induced mitochondrial dysfunction and steroid disorders in GCs, which provides new insights into the role of MT in ATR-induced reproductive capacity and species conservation in birds.

Identification of potentially suitable areas for nucleosides of Pinellia Ternata (Thunb.) Breit using ecological niche modeling.

Pinellia ternata, a traditional Chinese medicine, is well-renowned for its effectiveness in treating sickness such as coughs with excessive phlegm, vomiting, and nausea. The nucleoside components of P. ternata have been shown to have antitumor activity. Identifying potential growth areas of high-quality P. ternata based on the content of five nucleoside components and the identification of climatic features suitable for the growth of P. ternata will help to conserve P. ternata resources with targeted bioactive compounds. Using high-performance liquid chromatography (HPLC), we determined five nucleoside components, uridine, guanosine, adenosine, inosine, and thymidine, at 27 sampling points of P. ternata collected from 21 municipalities of 11 provinces in China. We used ecological niche modeling to identify the major environmental factors associated with the high metabolite content of P. ternata, including precipitation of the warmest quarter, annual mean temperature, annual precipitation, and isothermality. Areas with high suitability for the five nucleosides were found in Hebei, Shandong, Shanxi, Gansu, Sichuan, Guizhou, and Hubei Provinces. Under the RCP 2.6, RCP 4.5, and RCP 8.5 scenarios, the areas with a suitable distribution decreased and some areas with high suitability became areas with low suitability. Overall, our findings advance our knowledge of the ecological impacts of climate change and provide a valuable reference for conserving and sustainably developing high-quality P. ternata resources in the future.

Corrigendum: An integrative pharmacology model for decoding the underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid arthritis.

[This corrects the article DOI: 10.3389/fphar.2022.801350.].

Covalent immobilization of tyrosinase on magnetic multi-walled carbon nanotubes for inhibitor screening.

The inhibition of tyrosinase is considered to be a common therapeutic strategy for some hyperpigmentation disorders. Screening of tyrosinase inhibitors is of great significance to the treatment of pigmentation diseases. In this study, tyrosinase was covalently immobilized on magnetic multi-walled carbon nanotubes for the first time, and the immobilized tyrosinase was applied for ligand fishing of tyrosinase inhibitors from complex medicinal plants. The immobilized tyrosinase was characterized by transmission electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometry, and thermo-gravimetric analyzer, which indicated that tyrosinase was immobilized onto magnetic multi-walled carbon nanotubes. The immobilized tyrosinase showed better thermal stability and reusability than the free one. The ligand was fished out from Radix Paeoniae Alba and identified as 1,2,3,4,6-pentagalloylglucose by ultra-performance liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. 1,2,3,4,6-pentagalloylglucose was found to be a tyrosinase inhibitor with similar half maximal inhibitory concentration values of 57.13 ± 0.91 µM compared to kojic acid (41.96 ± 0.78 µM). This work not only established a new method for screening tyrosinase inhibitors but also holds considerable potential for exploring the new medicinal value of medicinal plants.

C:N:P stoichiometric characteristics of mosses in Picea crassifolia forest in Helan Mountains, Ningxia, China.

To explore the stoichiometric characteristics of C, N and P and adaptive mechanism of mosses in mountain forest ecosystems, we set up 15 plots along the altitude gradient in Picea crassifolia forest in Helan Mountains, Ningxia. We analyzed the C:N:P stoichiometry of moss aboveground tissues and its relationship with environmental factors. The results showed the mean values of C, N and P concentration in moss aboveground tissues were 336.67, 20.31 and 0.66 mg·g-1, respectively. The mean value of aboveground tissue N:P was 33.4, indicating that the growth of mosses was limited by P. The C concentration in the aboveground tissues of mosses was positively correlated with soil total nitrogen concentration and negatively correlated with soil total phosphorus concentration. The N concentration in aboveground tissues of mosses was significantly negatively correlated with soil organic carbon and soil total nitrogen concentrations. Results of redundancy analysis showed that the interpretation rate of environmental factors on the stoichiometry was 48.5%, with canopy closure, soil total nitrogen and soil total phosphorus as the main factors. Canopy closure was the main environmental factor affecting the growth of mosses in P. crassifolia forest in Helan Mountains. High canopy closure facilitated the growth of mosses.

TiO2-based catalytic systems for the treatment of airborne aromatic hydrocarbons.

Among diverse strategies to manage air quality, catalytic oxidation has been a widely used option to mitigate diverse pollutants such as aromatic volatile organic compounds (VOCs), especially benzene, toluene, and xylene (BTX). For such applications, TiO2-based catalysts have drawn significant research attention for their prominent photo/thermal catalytic activities and photochemical stability. This review has been organized to elaborate on the recent developments achieved in the thermocatalytic, photocatalytic, and photothermal applications of metal/non-metal doped TiO2 catalysts towards BTX vapors and their reaction mechanisms. The performance of the reported TiO2-based catalysts has also been analyzed based on multiple computational metrics such as reaction rate (r), quantum yield (QY), space-time yield, and figure of merit (FOM). At last, the research gap and prospects in the catalytic treatment of BTX are also discussed in association with the feasibility and utility of TiO2-based catalysts in air purification applications.

Quantification of promoting efficiency and reducing toxicity of Traditional Chinese Medicine: A case study of the combination of Tripterygium wilfordii hook. f. and Lysimachia christinae hance in the treatment of lung cancer.

Traditional Chinese medicine (TCM) usually acts in the form of compound prescriptions in the treatment of complex diseases. The herbs contained in each prescription have the dual nature of efficiency and toxicity due to their complex chemical component, and the principle of prescription is usually to increase efficiency and reduce toxicity. At present, the studies on prescriptions have mainly focused on the consideration of the material basis and possible mechanism of the action mode, but the quantitative research on the compatibility rule of increasing efficiency and reducing toxicity is still the tip of the iceberg. With the extensive application of computational pharmacology technology in the research of TCM prescriptions, it is possible to quantify the mechanism of synergism and toxicity reduction of the TCM formula. Currently, there are some classic drug pairs commonly used to treat complex diseases, such as Tripterygium wilfordii Hook. f. with Lysimachia christinae Hance for lung cancer, Aconitum carmichaelii Debeaux with Glycyrrhiza uralensis Fisch. in the treatment of coronary heart disease, but there is a lack of systematic quantitative analysis model and strategy to quantitatively study the compatibility rule and potential mechanism of synergism and toxicity reduction. To address this issue, we designed an integrated model which integrates matrix decomposition and shortest path propagation, taking into account both the crosstalk of the effective network and the propagation characteristics. With the integrated model strategy, we can quantitatively detect the possible mechanisms of synergism and attenuation of Tripterygium wilfordii Hook. f. and Lysimachia christinae Hance in the treatment of lung cancer. The results showed the compatibility of Tripterygium wilfordii Hook. f. and Lysimachia christinae Hance could increase the efficacy and decrease the toxicity of lung cancer treatment through MAPK pathway and PD-1 checkpoint pathway in lung cancer.

Saccharides from Arctium lappa L. root reduce platelet activation and thrombus formation in a laser injury thrombosis mouse model.

Arctium lappa L., also known as burdock, is a popular medicinal plant in traditional Chinese medicine due to its potential therapeutic properties. Saccharides from Arctium lappa L. root (ALR-S) have been extensively studied for their anti-inflammatory and anti-diabetes effects. Platelets play a pivotal role in thrombosis. The present study describes the effects of ALR-S on platelet activation and thrombosis using a laser injury thrombosis in vivo model. The study also measured the effects of ALR-S on platelet activation by analysing aggregation, ATP release, platelet spreading, adhesion and clot retraction in vitro. Specifically, the effects were ALR-S concentration-dependent inhibition of platelet aggregation and ATP release. Activated platelets pretreated with ALR-S showed diminished CD62P expression levels and fibrinogen binding, as measured by flow cytometry. ALR-S inhibited platelet spreading on fibrinogen and adhesion on collagen under shear. ALR-S attenuated platelet activation by decreasing oxidative stress and thrombus formation. These results demonstrated the antiplatelet effects of ALR-S, suggesting the antithrombotic and cardiovascular protective activities of ALR-S as a functional food.

An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis.

As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacological studies showed that Ermiao Powder, which consists of Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD), can be used in the treatment of RA. Currently, most studies focus on the anti-inflammatory mechanism of PAR and ALD and are less focused on their coordinated molecular mechanism. In this research, we established an integrative pharmacological strategy to explore the coordinated molecular mechanism of the two herbs of Ermiao Powder in treating RA. To explore the potential coordinated mechanism of PAR and ALD, we firstly developed a novel mathematical model to calculate the contribution score of 126 active components and 85 active components, which contributed 90% of the total contribution scores that were retained to construct the coordinated functional space. Then, the knapsack algorithm was applied to identify the core coordinated functional components from the 85 active components. Finally, we obtained the potential coordinated functional components group (CFCG) with 37 components, including wogonin, paeonol, ethyl caffeate, and magnoflorine. Also, functional enrichment analysis was performed on the targets of CFCG to explore the potential coordinated molecular mechanisms of PAR and ALD. The results indicated that the CFCG could treat RA by coordinated targeting to the genes involved in immunity and inflammation-related signal pathways, such as phosphatidylinositol 3­kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, and nuclear factor-kappa B signaling pathway. The docking and in vitro experiments were used to predict the affinity and validate the effect of CFCG and further confirm the reliability of our method. Our integrative pharmacological strategy, including CFCG identification and verification, can provide the methodological references for exploring the coordinated mechanism of TCM in treating complex diseases and contribute to improving our understanding of the coordinated mechanism.

Metabolic-based insecticide resistance mechanism and ecofriendly approaches for controlling of beet armyworm Spodoptera exigua: a review.

The beet army worm, Spodoptera exigua, is a widely distributed polyphagous pest of economically important crops worldwide. The management of this pest insect continues to face many challenges. Despite synthetic chemicals posing a serious threat to the environment, these remain the conventional approach for controlling S. exigua in the field. An over-reliance on chemical control has not only led to selection for resistance to insecticides and to a reduction of natural enemies, but has also polluted various components of ecosystem. Given these increasing pressures on the ecosystem, there is a need to implement integrated pest management (IPM) approaches exploiting a wider range of tools (biotechnological approaches, microbial control, biological control, cultural control, and use of host plant resistance) for an alternative to chemical control. The IPM approach can not only reduce the hazard of chemical residues in the environment and associated health problems, but may also provide best strategies to control insect pests. This review synthesizes published information on insecticide resistance of S. exigua and explores alternative IPM approaches to control S. exigua.

Anti-osteoporosis effect of Semen Cuscutae in ovariectomized mice through inhibition of bone resorption by osteoclasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae, called Tu-si-zi in Chinese, is a kind of dried mature seed in the Convolvulaceae family. It mainly distributes in China, Korea, Pakistan, Vietnam, India and Thailand. It is used as a kidney-tonifying drug for treatment of aging related diseases such as osteoporosis in traditional Chinese medicine. However, the exact mechanisms on bone resorption are poorly studied. AIM OF THE STUDY: The aim of this study was to investigate the potential effect of Semen Cuscutae on ovariectomy (OVX)-induced osteoporosis in mice and clarify the exact mechanisms by which Semen Cuscutae exert the anti-osteoporosis effect. MATERIALS AND METHODS: Qualitative and quantitative analyses of Semen Cuscutae were performed by UPLC-Q-TOF-MS and HPLC-MS/MS, respectively. Changes in bone mineral density (BMD) induced by OVX in mice were measured by dual-energy X-ray absorptiometry and micro-computed tomography (µCT). Tartrate-resistant acid phosphatase (TRAP) staining as well as hematoxylin and eosin (HE) staining were used to observe bone microarchitectural changes. ELISA kits were used to assess the therapeutic effects of Semen Cuscutae on the serum levels of osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP-5b), and receptor activator of nuclear factor-κB (RANKL). The effect of Semen Cuscutae on primary cell viability was assessed using CCK-8 and anti-tartrate phosphatase assays. TRAP staining and actin ring staining were used to observe the effect of Semen Cuscutae on osteoclast differentiation. Western blotting was used to measure the effects of Semen Cuscutae on expressions of NFATC1, c-Src kinase, and c-fos. RESULTS: Results from UPLC-Q-TOF-MS showed that the main components of Semen Cuscutae were flavonoid compounds that included quercitrin, quercetin, hyperoside, caffeic acid, rutin, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercetin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, and astragalin. After the Semen Cuscutae extract was orally administered to OVX mice, bone density increased (P < 0.01) and bone microstructure was significantly improved (P < 0.01 or 0.05). Additionally, Semen Cuscutae exhibited a significant descending effect in the levels of serum TRACP-5b and RANKL, while there was a significant increase in OPG in the Semen Cuscutae group compared with the OVX group, especially at high doses. Moreover, we found that increasing of c-fos, c-Src kinase, and NFATC1 protein expressions were reversed by Semen Cuscutae in vitro and in vivo. CONCLUSIONS: Our results showed that Semen Cuscutae exhibited anti-osteoporosis effects through the c-fos/c-Src kinase/NFATC1 signaling pathway.

Tracing Key Molecular Regulators of Lipid Biosynthesis in Tuber Development of Cyperus esculentus Using Transcriptomics and Lipidomics Profiling.

Cyperus esculentus is widely representing one of the important oil crops around the world, which provides valuable resources of edible tubers called tiger nut. The chemical composition and high ability to produce fats emphasize the role of tiger nut in promoting oil crop productivity. However, the underlying molecular mechanism of the production and accumulation of lipids in tiger nut development still remains unclear. Here, we conducted comprehensive transcriptomics and lipidomics analyses at different developmental stages of tuber in Cyperus esculentus. Lipidomic analyses confirmed that the accumulation of lipids including glycolipids, phospholipids, and glycerides were significantly enriched during tuber development from early to mature stage. The proportion of phosphatidylcholines (PC) declined during all stages and phosphatidyl ethanolamine (PE) was significantly declined in early and middle stages. These findings implied that PC is actively involved in triacylglycerol (TAG) biosynthesis during the tubers development, whereas PE may participate in TAG metabolism during early and middle stages. Comparative transcriptomics analyses indicated several genomic and metabolic pathways associated with lipid metabolism during tuber development in tiger nut. The Pearson correlation analysis showed that TAG synthesis in different developmental stages was attributed to 37 candidate transcripts including CePAH1. The up-regulation of diacylglycerol (DAG) and oil content in yeast, resulted from the inducible expression of exogenous CePAH1 confirmed the central role of this candidate gene in lipid metabolism. Our results demonstrated the foundation of an integrative metabolic model for understanding the molecular mechanism of tuber development in tiger nut, in which lipid biosynthesis plays a central role.

The study on the clinical effectiveness and safety of traditional Chinese medicine acupoint catgut embedding guided by musculoskeletal ultrasound in the treatment of nerve root sciatica: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Nerve root sciatica (NRS) is a common orthopedic disease, which usually occurs between 20 and 40 years of age, and the incidence rate is increasing year by year and is being younger. The disease has no special effect of treatment, clinically generally taking the symptomatic treatment, such as taking short-term glucocorticoids, sedatives, analgesics, and so on. Long-term use of drugs will adversely affect the patient's gastrointestinal tract, liver, and kidney function. The surgical treatment has a high risk of surgery, high cost, side effects, and other problems, so the choice of treatment method has always been a difficult problem in clinical and scientific research. The study shows that 90% of patients with sciatica can be cured by non-surgical treatment, so conservative therapy is often used in the treatment of sciatica, traditional Chinese medicine treatment methods in the treatment of NRS has been widely used, which has achieved good results, but there is no evidence of evidence-based medicine. Therefore, this study uses systematic evaluation to conduct the scientific evaluation of the clinical effectiveness and safety of traditional Chinese medicine acupoint catgut embedding guided by musculoskeletal ultrasound in the treatment of NRS, and provide evidence-based medical evidence support for the treatment of NRS. METHODS: Using the computer to retrieve the PubMed, ScienceDirect, Web of Science, Embase, Cochrane Library, CNKI, VIP, WANFANG Database, and CBM. Using the subject words and terminology words to retrieve the Chinese-English database and retrieve a randomized controlled study on the clinical effectiveness and safety of traditional Chinese medicine acupoint catgut embedding guided by musculoskeletal ultrasound in the treatment of NRS, and the range of search time is January 1990 to January 2021. The searched literature is screened and evaluated by two researchers respectively according to the inclusion and exclusion criteria. If there is disagreement, discussing it with the third researcher to determine the final inclusion of the literature. Using the RevMan 5.3 software to conduct the meta-analysis. RESULTS: This study will compare the effectiveness and safety of traditional Chinese medicine acupoint catgut embedding guided by musculoskeletal ultrasound in the treatment of NRS. CONCLUSION: The results of this study will be published in internationally influential academic journals to provide evidence-based medical evidence for the clinical effectiveness and safety of traditional Chinese medicine acupoint catgut embedding in the treatment of NRS. ETHICS AND DISSEMINATION: This study does not involve specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/Q492E.

Supportive psychological intervention on psychological disorders in clinical medicine students with English Learning Difficulties: A protocol of systematic review.

BACKGROUND: This study aims to examine the effect of supportive psychological intervention (SPI) on psychological disorders (PD) in clinical medicine students (CMS) with English Learning Difficulties (ELD). METHODS: We will perform a comprehensive literature search from the following databases: Cochrane Library, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All databases will be performed from their inception to the present without language limitation by 2 independent reviewers. We will also look for grey literature, such as conference proceedings, dissertations or theses. Newcastle-Ottawa Scale will be used to assess study quality, and RevMan 5.3 software will be applied to carry out statistical analysis. RESULTS: This study will summarize the most recent evidence to assess the effect of SPI on PD in CMS with ELD. CONCLUSION: This study may provide helpful evidence of SPI on PD in CMS with ELD. OSF REGISTRATION NUMBER:: osf.io/tah2s.

Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus.

BACKGROUND: The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating . The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. PURPOSE: The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. METHODS: In our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. RESULTS: Results showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD = (7.31 ± 0.62)e-7 M and (4.82 ± 0.87)e-7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. CONCLUSIONS: CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection.