Protective effect of ginsenoside Rb1 against aconitine cardiotoxicity studied by myocardial injury, action potential, and calcium signaling.

Aconitine is the main active component of Aconitum plants. Although aconitine has effects that include strengthening the heart, analgesia, anti-tumor, and immune-regulating effects, aconitine has both efficacy and toxicity, especially cardiotoxicity. Severe effects can include arrhythmia and cardiac arrest, which limits the clinical application of aconitine-containing traditional Chinese medicine. Ginsenoside Rb1(Rb1) is mainly found in plants, such as ginseng and Panax notoginseng, and has cardiovascular-protective and anti-arrhythmia effects. This study aimed to investigate the detoxifying effects of Rb1 on aconitine cardiotoxicity and the electrophysiological effect of Rb1 on aconitine-induced arrhythmia in rats. Pathological analysis, myocardial enzymatic indexes, and Western blotting were used to investigate the ameliorating effect of Rb1 on aconitine cardiotoxicity. Optical mapping was used to evaluate the effect of Rb1 on action potential and calcium signaling after aconitine-induced arrhythmia. Rb1 inhibited pathological damage caused by aconitine, decreased myocardial enzyme levels, and restored the balance of apoptotic protein expression by reducing the expression of Bax and cleaved caspase 3 and increasing the expression of Bcl-2, thereby reducing myocardial damage caused by aconitine. Rb1 also reduced the increase in heart rate caused by aconitine, accelerated action potential conduction and calcium signaling, and reduced the dispersion of action potential and calcium signal conduction. Rb1 reduced the cardiotoxicity of aconitine by attenuating aconitine-induced myocardial injury and inhibiting the aconitine-induced retardation of ventricular action potential and calcium signaling in rats.

Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2-positive breast cancer.

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.

Leech extract alleviates idiopathic pulmonary fibrosis by TGF-ß1/Smad3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear. AIM OF THE STUDY: Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components. MATERIALS AND METHODS: In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3-10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-ß1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays. RESULTS: Using TGF-ß1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis. CONCLUSIONS: Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-ß1/Smad3 signaling pathway.

The effects of swLORETA Z-score neurofeedback for patients comorbid with major depressive disorder and anxiety symptoms.

BACKGROUND: Patients with major depressive disorder (MDD) exhibit atypical brain activities in the frontal, temporal, and parietal lobes. The study aimed to investigate the effects of standardized weighted low-resolution electromagnetic tomography Z-score neurofeedback (swLZNFB) on symptoms of depression and anxiety, electroencephalography (EEG) parameters, and deep brain activities in patients with MDD. METHOD: Forty-eight patients with MDD comorbid with anxiety symptoms were assigned to the swLZNFB group and the control group. Participants completed the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) and a 5-minute resting EEG at the pre-and post-tests. The swLZNFB group received ten sessions of one-hour treatment twice weekly. The control group received treatment as usual. The scores for BDI-II and BAI, number of EEG abnormalities, percentage of EEG abnormalities, and current source density (CSD) measured in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and amygdala were compared at pre-and post-tests between the two groups. RESULTS: There were decreased scores of BDI-II and BAI, number of EEG abnormalities, and percentage of EEG abnormalities at post-test compared with pre-test in the swLZNFB group, and lower scores of BDI-II and BAI at post-test in the swLZNFB group compared with the control group. Moreover, decreased CSD of beta1 and beta3 in the PFC, ACC, PCC, and amygdala at post-test compared to pre-test in the swLZNFB group. LIMITATIONS: Not a randomized controlled trial. CONCLUSION: Ten sessions of swLZNFB reduced clinical symptoms and atypical brain activities, it serves as a potential psychological intervention for patients with MDD.

Evaluating the role of Shujing Tongdu massage in enhancing wound recovery and alleviating spinal disease symptoms: A randomized controlled trial.

A randomized, controlled clinical trial was conducted from 2022 to 2023 at a hospital specializing in Traditional Chinese Medicine in Shanghai. A total of 564 participants were allocated into control and intervention groups in order to determine the effectiveness of Shujing Tongdu massage on patients with chronic lesions or spinal disorders. No significant differences were observed in baseline characteristics between the groups; age, gender and condition type were all distributed in a comparable manner. Following the implementation of Shujing Tongdu massage therapy twice weekly for the duration of 12 weeks, intervention group exhibited noteworthy enhancements. Significantly, rate of lesion healing achieved in the intervention group increased by 30%, while it merely improved by 10% in the control group. The intervention group exhibited decrease in pain intensity from 6.5 to 4.2, whereas control group demonstrated comparatively smaller reduction from 6.7 to 6.0. Range of motion in the intervention group increased substantially from 45 to 60 degrees, whereas it increased from 44 to 46 degrees in the control group. In the intervention group, Quality of Life scores increased from 50 to 75, exceeding the increase of 58 in the control group. There was significant rise in the Mental Well-being Index for intervention group, from 60 to 80, in contrast to rise of 64 from 62 in the control group. Statistically significant outcomes were determined, establishing the massage therapy's efficacy. Mild discomfort and muscle soreness were the most frequent adverse effects in the intervention group, whereas vertigo was more prevalent in the control group. Based on the findings of this research, Shujing Tongdu massage therapy effectively promoted wound healing and mitigated symptoms associated with spinal disorders, indicating its potential as the supplementary therapeutic modality in clinical environments.

Catalpol rescues LPS-induced cognitive impairment via inhibition of NF-Κb-regulated neuroinflammation and up-regulation of TrkB-mediated BDNF secretion in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Septic-associated encephalopathy (SAE) is a key manifestation of sepsis. Nevertheless, specific treatment for SAE is still lacking. Catalpol is an active component derived from Rehmanniae Radix, and has been demonstrated to be a potential neuroprotective agent. However, its effect on SAE still needs to be fully explored. AIM: To address the benefits of catalpol on post-sepsis cognitive deterioration and related mechanisms. MATERIALS AND METHODS: Novel object recognition test, temporal order task, histopathology, and immunochemistry were applied to address the benefits of catalpol on LPS-triggered post-sepsis cognitive decline in mice. Xuebijing injection (10 ml/kg) has been utilized as a positive control in the above animal studies. After treatment, the catalpol content in the hippocampus was determined using LC-MS/MS. Finally, the mechanisms of catalpol were further assessed in BV2 and PC12 cells in vitro using Western blot, RT-PCR, flow cytometry, molecular docking tests, thermal shift assay, transmission electron microscopy, and immunofluorescence analysis. RESULTS: Behavior tests showed that catalpol therapy could lessen the cognitive impairment induced by LPS damage. HE, Nissl, immunofluorescence, transmission electron microscopy, and Golgi staining further reflected that catalpol treatment could restore lymphocyte infiltration, blood-brain barrier (BBB) degradation, and the decreasing complexity of dendritic trees. According to LC-MS/MS analysis, catalpol had a 136 ng/mg concentration in the hippocampus. In vitro investigation showed that catalpol could inhibit microglia M1 polarization via blocking NF-κB phosphorylation, translocation and then reducing inflammatory cytokine release in BV2 microglia cells. Brain-derived neurotrophic factor (BDNF) release up-regulation and TrkB pathway activation were observed in the catalpol treatment group in vivo and in vitro. The effect of catalpol on enhancing BDNF expression was inhibited by the specific inhibitor of TrkB (GNF-5837) in PC12 cells. Further molecular docking tests showed that catalpol formed weak hydrophobic bonds with TrkB. Besides, thermal shift assay also reflected that catalpol incubation caused a considerable change in the melting temperature of the TrkB. CONCLUSION: Catalpol alleviates LPS-triggered post-sepsis cognitive impairment by reversing neuroinflammation via blocking the NF-κB pathway, up-regulating neurotrophic factors via the activation of TrkB pathway, and preserving BBB integrity.

Plant exosomes fused with engineered mesenchymal stem cell-derived nanovesicles for synergistic therapy of autoimmune skin disorders.

Existing therapeutics for autoimmune diseases remain problematic due to low efficacy, severe side effects, and difficulties to reach target tissues. Herein, we design multifunctional fusion nanovesicles that can target lesions for the treatment of autoimmune skin diseases. The grapefruit-derived exosome-like nanovesicles (GEVs) with anti-inflammatory and antioxidant effects are first encapsulated with CX5461, an immunosuppressant with anti-proliferative properties to form GEV@CX5461. In order to enhance therapeutic efficiency and safety, GEV@CX5461 are then fused with CCR6+ nanovesicles derived from membranes of engineered gingiva-derived mesenchymal stem cells (GMSCs). The resulting FV@CX5461 not only maintain the bioactivity of GEVs, CX5461, and GMSC membranes but also home to inflamed tissues rich in chemokine CCL20 through the chemotaxis function of CCR6 on FVs. Moreover, FV@CX5461 reduce the secretion of inflammatory factors, calm down Th17 cell activation, and induce Treg cell infiltration. Finally, impressive therapeutic efficiency in both psoriasis and atopic dermatitis disease models is demonstrated using FV@CX5461 to reshape the unbalanced immune microenvironment. A nanotherapeutic drug delivery strategy is developed using fusion nanovesicles derived from plant and animal cells with high clinical potential.

Effects of heart rate variability biofeedback (HRVBFB) on sleep quality and depression among methamphetamine users.

Methamphetamine is garnering concern due to its increasing use worldwide. Depression and sleep quality are major mental health issues in substance users. Heart rate variability biofeedback (HRVBFB) has shown promising results in terms of reducing depression and increasing sleep quality. The present study aimed to explore the effects of HRVBFB on these two issues in methamphetamine users. Sixty-one methamphetamine users were enrolled and allocated randomly into a treatment as usual (TAU) group and a HRVBFB plus TAU group. The levels of depressive symptoms and sleep quality were assessed at intake, end of the intervention, and end of follow-up. Compared with baseline, the levels of depressive symptoms and poor sleep quality were decreased at the end of the intervention and follow-up in the HRVBFB group. The HRVBFB group exhibited a greater decrease in depressive symptoms and a better improvement in sleep quality than the TAU group. The associations of HRV indices with levels of depressive symptoms and poor sleep quality were different in the two groups. Our results showed that HRVBFB is a promising intervention for reducing depressive symptoms and improving sleep quality in methamphetamine users. The benefits with respect to depressive symptoms and poor sleep quality can extend beyond the end of HRVBFB intervention.

Microwave ablation versus radiofrequency ablation for patients with primary and secondary hyperparathyroidism: a meta-analysis.

OBJECTIVE: Thermal ablation, including microwave ablation (MWA) and radiofrequency ablation (RFA), has been recommended for the treatment of primary hyperparathyroidism (PHPT) and refractory secondary hyperparathyroidism (SHPT). This meta-analysis was conducted to evaluate the efficacy and safety of MWA and RFA in patients with PHPT and refractory SHPT. METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang were searched from inception to December 5, 2022. Eligible studies comparing MWA and RFA for PHPT and refractory SHPT were included. Data were analyzed using Review Manager software, version 5.3. RESULTS: Five studies were included in the meta-analysis. Two were retrospective cohort studies, and three were RCTs. Overall, 294 patients were included in the MWA group, and 194 patients were included in the RFA group. Compared with RFA for refractory SHPT, MWA had a shorter operation time for a single lesion (P < 0.01) and a higher complete ablation rate for a single lesion ≥ 15 mm (P < 0.01) but did not show a difference in the complete ablation rate for a single lesion < 15 mm (P > 0.05). There were no significant differences between MWA and RFA for refractory SHPT concerning parathyroid hormone (P > 0.05), calcium (P > 0.05), and phosphorus levels (P > 0.05) within 12 months after ablation, except that calcium (P < 0.01) and phosphorus levels (P = 0.02) in the RFA group were lower than those in the MWA group at one month after ablation. There was no significant difference between MWA and RFA concerning the cure rate of PHPT (P > 0.05). There were no significant differences between MWA and RFA for PHPT and refractory SHPT concerning the complications of hoarseness (P > 0.05) and hypocalcaemia (P > 0.05). CONCLUSION: MWA had a shorter operation time for single lesions and a higher complete ablation rate for large lesions in patients with refractory SHPT. However, there was no significant difference in efficacy and safety between MWA and RFA in cases of both PHPT and refractory SHPT. Both MWA and RFA are effective treatment methods for PHPT and refractory SHPT.

Insecticidal and Repellent Effects of the Essential Oils Extract from Zanthoxylum myriacanthum against Three Storage Pests.

The co-storage of two or more Chinese herbal medicines can effectively prevent the herbs from the damage by pests. Thus, it is important to protect herbs and crops to study Chinese herbal medicines and their medicinal components against storage pests. This study aimed to assess the insecticidal activities and repellent effect of essential oils (EOs) extracted from fruits at different periods from Zanthoxylum myriacanthum Wall. ex Hook. f. (1 h, 2 h, 3-5 h and 5-7 h), and their major compounds against three kinds of pests (Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila). The results of gas chromatography-mass spectrometer analysis revealed homomyrtenol (22.56 %, 28.01 %, 28.48 % and 28.41 %, respectively) and p-cymene (30.58 %, 13.95 %, 24.97 % and 6.85 %, respectively) were the common major compounds of the EOs at 1 h, 2 h, 3-5 h, and 5-7 h. m-Cymene contents in EOs of fruits, 1 h, 2 h and 3-5 h were 3.85 %, 0.95 %, 6.71 %, and 6.15 %, respectively. According to Principal component analysis (PCA), the composition of fruits' EO was significantly different from other EOs due to the different collection times. The bio-assays showed that EOs and major compounds were toxic to all three pests, but the fumigation effect on L. bostrychophila was not noticeable. EOs extracted at different times had a repellent effect on the three pests at the highest concentration (78.63 nL/cm2 ), but the attractive effects of the EOs of 3-5 h, 5-7 h, and p-cymene were observed at the low concentrations (3.15, 0.63 and 0.13 nL/cm2 ). Our results suggest that Z. myriacanthum have the potential to be developed as biological insecticides.

Research advances in mechanism of lipid infiltration of coronary heart disease and simultaneous treatment of phlegm and blood stasis based on phlegm-blood stasis correlation theory / 中国中药杂志

Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.

Exploring the Two Herb Combination Strategy to Treat Injured PC12 Cells.

In view of the advantages of the combination of traditional Chinese medicine (TCM) in the treatment of cerebral ischemia, we studied the differences in the efficacy and mechanism between the preparation combination and the component combination in order to explore the two herb combination strategy to treat injured PC12 cells. Cobalt chloride (CoCl2) combined with a glucose-free medium was employed to induce oxidative damage of PC12 cells. Then, the optimal combination of Astragalus mongholicus (Ast) and Erigeron breviscapus (Eri) injection was selected and combined following uniform design methods after screening their safe and effective concentration on PC12 cells. Further, the component combination screened comprises 10 µM astragaloside A, 40 µM scutellarin, and 75 µM chlorogenic acid in two herbs. Then, MTT, Annexin V-FITC/PI, immunofluorescence, and Western blot analysis were used to evaluate the efficacy and mechanism of the preparation combination and the component combination on injured PC12 cells. The results showed that the optimal preparation combination for cell pro-survival was Ast injection and Eri capsule with a concentration of 6:1.8 (µM). The component combination (10 µM astragaloside A, 40 µM scutellarin, and 75 µM chlorogenic acid) was more effective than the preparation combination. Both combinations remarkably reduced apoptotic rate, the fluorescence intensity of caspase-3, and intracellular reactive oxygen species (ROS) level; meanwhile, they upregulated the expression levels of p-Akt/Akt, Bcl-2/Bax, and Nrf2. These effects were more evident in the component combination. In conclusion, both combinations can inhibit the injury induced by CoCl2 combined with a glucose-free medium on PC12 cells, thus promoting cell survival. However, the efficiency of the component combination over the preparation combination may be due to its stronger regulation of the PI3K/Akt/Nrf2 signaling pathway related to oxidative stress and apoptosis.

Investigation of the Potential Mechanism of Danggui Shaoyao San for the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD) with Network Pharmacology and Molecular Docking.

BACKGROUND: Danggui Shaoyao San (DSS) is a well-known herbal formula, which has been widely used in the treatment of non-alcoholic fatty liver disease (NAFLD). However, the potential mechanisms of DSS for NAFLD remain unknown. OBJECTIVE: Our study aims to explore the active components and potential molecular mechanisms of DSS for the treatment of NAFLD. METHODS: In this study, network pharmacology and molecular docking were performed to predict the active ingredients, potential targets and molecular mechanisms of DSS for the treatment of NAFLD. RESULTS: The 28 active components and 27 potential targets of DSS associated with NAFLD were identified, and five components most closely associated with NAFLD were beta-sitosterol, kaempferol, hederagenin, 3ß-acetoxyatractylone, and sitosterol. DSS was involved in regulating pathways in cancer, AGE-RAGE signalling pathway in diabetic complications, IL-17 signalling pathway, NAFLD, hepatitis B, apoptosis, and hepatitis C. Additionally, IL-6, Caspase 3, RELA, PTGS2, and JUN might be the potential targets of DSS for NAFLD treatment. In addition, the results of molecular docking indicated that kaempferol and beta-sitosterol compounds could bind to the important targets. CONCLUSION: Our study systematically investigated the potential molecular mechanism of DSS for the treatment of NAFLD, which would potentially provide a new clinical approach for NAFLD.

A Pilot Randomized Control Study on Effect Brief Heart Rate Variability Biofeedback as a Complementary Treatment in Men with Methamphetamine Use Disorder.

The aims of this study were to investigate the efficacy of heart rate variability biofeedback (HRVBFB) intervention in terms of reducing craving, severity of dependence, and rate of positive methamphetamine urine testing in men taking part in a methamphetamine use disorder outpatient treatment program. Sixty-one adult men received either HRVBFB treatment plus treatment as usual (TAU) over four weeks or TAU only. Men receiving HRVBFB showed significantly greater reductions in craving, dependence severity, and the rate of positive methamphetamine urine testing at the end of the intervention and four weeks of follow-up. The analyses further showed that the levels of craving and dependence severity at treatment entry were predictive of changes in craving and dependence severity at the end of treatment and follow-up, respectively. The baseline status of a positive methamphetamine urine test only predicted a positive methamphetamine urine test at the end of treatment, not at the end of the follow-up period. Our results showed HRVBFB intervention has merits as an adjunct treatment to ameliorate cravings and reduce the severity of dependence experienced by persons with methamphetamine use disorder. An added value of HRVBFB intervention is the fact that it can be easily and affordably implemented in everyday life.

[Mechanism of Tibetan medicine Ershiwuwei Songshi Pills in regulating intestinal flora and improving non-alcoholic steatohepatitis].

This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.

[Mechanism of Tibetan medicine Ershiwuwei Songshi Pills against liver injury induced by acetaminophen in mice based on Keap1/Nrf2 and TLR4/NF-κB p65 signaling pathways].

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.

[Serum metabolomics of Tibetan medicine Ershiwuwei Songshi Pills against chronic cholestasis in mice].

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.

Effect of traditional Chinese medicine Bailing capsule on renal anemia in maintenance hemodialysis patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Renal anemia (RA) is one of the most common complications in patients with end-stage renal disease, and it is also one of the reasons for the decline of quality of life and functional status in patients with end-stage renal disease. Traditional treatment methods often fail to achieve satisfactory therapeutic effects, so it is very necessary to find effective adjuvant treatment methods. Bailing capsule (BLC), a traditional Chinese medicine, which has been widely used in the treatment of RA in maintenance hemodialysis patients, but a systematic review of the efficacy and safety of this drug is currently lacking. Therefore, this study used meta-analysis to evaluate the efficacy and safety of BLC in the treatment of RA, in order to provide guidance for finding effective auxiliary methods for the treatment of RA in maintenance hemodialysis patients (MHP). METHODS: Using the computer to retrieve PubMed, EMbase, Cochrane Library, CNKI, VIP Database, WANFANG Database, SinoMed from 1990 to 2021 and collecting the clinical randomized controlled trial and retrospective cohort study of BLC in the treatment of RA in MHP. Two researchers independently read and screened the literature, followed by evaluating the retrospective cohort studies that met the selection criteria using the Newcastle-Ottawa Scale (NOS) scale. The randomized controlled trial used the Cochrane manual standards to assess the risk of bias, and the RevMan 5.3 software was used to conduct a meta-analysis of the result data. RESULTS: This study will use the method of meta-analysis to evaluate the clinical efficacy and incidence of adverse reactions of BLC in the treatment of RA in MHP through the primary and secondary outcome indicators. CONCLUSION: The results of this study will help clinicians find safe and effective adjuvant therapy in the treatment of RA in MHP. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/732KP (https://osf.io/732kp).

Effects of Exergaming-Based Tai Chi on Cognitive Function and Dual-Task Gait Performance in Older Adults With Mild Cognitive Impairment: A Randomized Control Trial.

Background: Declined cognitive function interferes with dual-task walking ability and may result in falls in older adults with mild cognitive impairment (MCI). The mind-body exercise, Tai Chi (TC), improves cognition and dual-task ability. Exergaming is low-cost, safe, highly scalable, and feasible. Whether the effects of exergaming-based TC is beneficial than traditional TC has not been investigated yet. Objectives: The objective of this study was to investigate effects of exergaming-based TC on cognitive function and dual-task walking among older adults with MCI. Methods: Fifty patients with MCI were randomly assigned to an exergaming-based TC (EXER-TC) group, a traditional TC (TC) group, or a control group. The EXER-TC and TC groups received 36 training sessions (three, 50-min sessions per week) during a 12-week period. The control group received no intervention and were instructed to maintain their usual daily physical activities. The outcome variables measured included those related to cognitive function, dual-task cost (DTC), and gait performance. Results: The EXER-TC and TC groups performed better than the control group on the Chinese version of the Stroop Color and Word Test, the Trail Making Test Parts A and B, the one-back test, gait speed, and DTC of gait speed in cognitive dual-task conditions after training. However, there were no significant differences between the EXER-TC and TC groups. Compared with the control group, only the EXER-TC group experienced beneficial effects for the Montreal Cognitive Assessment. Conclusion: EXER-TC was comparable to traditional TC for enhancement of dual-task gait performance and executive function. These results suggested that the EXER-TC approach has potential therapeutic use in older adults with MCI.