Electroacupuncture Activated Impaired Brain Areas and Improved Mental Status and Sleep Quality in Primary Insomnia Patients.

Objective: This study aimed to investigate the specific neurological mechanisms underlying the effects of electroacupuncture at Shenmen (Heart 7) with Neiguan (Pericardium 6) acupoints in patients with primary insomnia (PI). We sought to understand these mechanisms by comparing changes in areaal homogeneity (ReHo) before and after treatment in PI patients and healthy controls (HC). Methods: Between November 2019 and November 2021, we recruited 17 primary insomnia patients (PI group) and 20 matched healthy controls (HC group) as study subjects from Zhaoqing First People's Hospital. Before electroacupuncture treatment, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) assessments. Resting-state magnetic resonance imaging (MRI) scans were conducted before and after two sessions of electroacupuncture at Shenmen and Neiguan acupoints. Results: Before treatment, primary insomnia patients showed higher PSQI (χ2=1.964; P = .017), HAMA (χ2=2.016; P = .027), and HAMD scores (χ2=2.367; P = .013) compared to healthy controls, and increased ReHo values were observed in the left amygdala, bilateral middle temporal gyrus, and left posterior cingulate gyrus in PI patients, while decreased ReHo values were found in the left posterior cingulate gyrus, right middle frontal gyrus, and right precuneus. After treatment, ReHo values increased in the left superior frontal gyrus, right parahippocampal gyrus, and right cingulate gyrus, while they decreased in the left amygdala and right angular gyrus. Primary insomnia disrupts brain areas in the default network, salience network, and parts of the affective cognitive network. Conclusion: Electroacupuncture at Shenmen and Neiguan acupoints partially activated impaired brain areas in patients with primary insomnia, leading to improvements in mental status and sleep quality. This offers a novel perspective for the clinical treatment of primary insomnia.

Estradiol is a key candidate for treating Ankylosing Spondylolisthesis with Traditional Chinese Medicine.

Some Traditional Chinese Medicine (TCM) has shown anti-inflammatory and immunosuppressive effects on Ankylosing Spondylitis (AS) treatment. Wan Bikang (WBK) and Wan Biqing (WBQ) are two traditional empirical formulas for AS. However, the mechanism of their effects on AS is largely unknown. This study deciphered the underlying common molecular mechanisms of these TCM treatments for AS. The ultra-high-performance liquid chromatography-triple/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) assays were employed to detect herbal ingredients. Target proteins of herbal ingredients were identified by ChEMBL Database. To infer the relationships between ingredients and AS-related proteins, network pharmacology was employed. Protein-protein interaction (PPI) network and core target analyses were carried out with tools Cytoscape and STRING. To find out the molecular basis and target of AS, molecular docking and an in vitro experiment were also conducted. It is found that estradiol may participate in the treatment of AS via the inhibition of inflammatory factors, and Estrogen Receptor 1 (ESR1) appears to be a key target. This research offers insight into the therapeutic mechanism of TCM formulas for AS and furthers our understanding of TCM pharmacology.

Combined supplementation with Lactobacillus sp. and Bifidobacterium thermacidophilum isolated from Tibetan pigs improves growth performance, immunity, and microbiota composition in weaned piglets.

Probiotics, such as Lactobacillus and Bifidobacterium, promote growth in piglets by modulating gut microbiota composition and improving the host immune system. A strain of Lactobacillus sp. and Bifidobacterium thermacidophilum were previously isolated from fresh feces of Tibetan pigs. The effects of these isolated strains on growth performance, intestinal morphology, immunity, microbiota composition, and their metabolites were evaluated in weaned piglets. Thirty crossbred piglets were selected and fed either a basal diet (CON), a basal diet supplemented with aureomycin (ANT), or a basal diet supplemented with Lactobacillus sp. and B. thermacidophilum (LB) for 28 d. The piglets in the ANT and LB groups had significantly higher body weight gain than those in the CON group (P < 0.05). Piglets in the ANT and LB groups had regularly arranged villi and microvilli in the small intestine. Furthermore, they had improved immune function, as indicated by decreased serum concentrations of inflammatory cytokines (P < 0.05), improved components of immune cells in the blood, mesenteric lymph nodes, and spleen. Additionally, metagenomic sequencing indicated a significant shift in cecal bacterial composition and alterations in microbiota functional profiles following Lactobacillus sp. and B. thermacidophilum supplementation. Metabolomic results revealed that the metabolites were also altered, and Kyoto Encyclopedia of Genes and Genomes analysis revealed that several significantly altered metabolites were enriched in glycerophospholipid and cholesterol metabolism (P < 0.05). Furthermore, correlation analysis showed that several bacterial members were closely related to the alterations in metabolites, including Bacteroides sp., which were negatively correlated with triglyceride (16:0/18:0/20:4[5Z,8Z,11Z,14Z]), the metabolite that owned the highest variable importance of projection scores. Collectively, our findings suggest that combined supplementation with Lactobacillus sp. and B. thermacidophilum significantly improved the growth performance, immunity, and microbiota composition in weaned piglets, making them prospective alternatives to antibiotics in swine production.

Probiotics such as Lactobacillus and Bifidobacterium have growth- and immunity-promoting effects in piglets. Thirty weaned piglets were selected and fed either a basal diet, a basal diet supplemented with aureomycin, or a basal diet supplemented with Lactobacillus sp. and Bifidobacterium thermacidophilum isolated from Tibetan pigs for 28 d. The results showed that combined supplementation with B. thermacidophilum and Lactobacillus sp. significantly improved growth performance, intestinal morphology, and immunity in weaned piglets, which is similar to piglets treated with antibiotics. They also improved cecal bacterial composition as indicated by the metagenomic sequencing results. Metabolomic results revealed that the altered metabolites were primarily enriched in glycerophospholipid and cholesterol metabolism. Correlation analysis showed that many bacterial members were closely related to the alterations of metabolites, suggesting B. thermacidophilum and Lactobacillus sp. exert effects via bacterial metabolism. Thus, Lactobacillus sp. and B. thermacidophilum could potentially be used as a prospective alternative of antibiotic growth promoters in piglets.

Serine Administration Improves Selenium Status, Oxidative Stress, and Mitochondrial Function in Longissimus Dorsi Muscle of Piglets with Intrauterine Growth Retardation.

Intrauterine growth retardation (IUGR) causes oxidative stress in the skeletal muscle. Serine and selenoproteins are involved in anti-oxidative processes; however, whether IUGR affects selenium status and whether serine has beneficial effects remain elusive. Here, we investigated the effects of serine administration on selenium nutritional status and oxidative stress in the longissimus dorsi muscle of piglets with IUGR. Six newborn Min piglets having normal birth weight were administered saline, and 12 IUGR piglets were either administered saline or 0.8% serine. The results showed a lower selenium content in skeletal muscle in IUGR piglets, which was restored after serine administration. IUGR piglets showed a disturbed expression of genes encoding selenoproteins, with decreased expression of GPX2, GPX4, TXNRD1, and TXNRD3 and increased expression of DIO1, DIO2, SELF, SELM, SELP, and SELW. Notably, serine administration restored the expression levels of these genes. In accordance with the changes in gene expression, the activity of GPX, TXNRD, and DIO and the content of GSH and SELP were also altered, whereas serine administration restored their contents and activities. Moreover, we observed severe oxidative stress in the skeletal muscle of IUGR piglets, as indicated by decreased GSH content and increased MDA and PC content, whereas serine administration alleviated these changes. In conclusion, our results indicate that IUGR piglets showed a disturbed expression of genes encoding selenoproteins, accompanied by severe oxidative stress. Serine administration can improve selenium status, oxidative stress, and mitochondrial function in the longissimus dorsi muscle of piglets with IUGR. These results suggest that serine could potentially be used in the treatment of IUGR in piglets.

Effects of two concentrations of dietary tribasic zinc sulfate on growth performance, gut morphology, and zinc transporter expression levels in pigs.

Tribasic zinc sulfate (TBZ) is insoluble in water and chemically less active than zinc sulfate, making it more suitable to be used in pig diet. To investigate the effects of TBZ on the growth performance, gut morphology, and zinc transporter expression levels, we performed a single-factor experiment and 168 pigs were allocated to three groups with seven pens per treatment. Pigs were either fed a basal diet without zinc supplementation (control group), or a basal diet supplemented with TBZ at 100 mg/kg diet (LTBZ group) or 1000 mg/kg diet (HTBZ group). We found that daily weight gain and feed intake were higher in the LTBZ group than in the HTBZ and control groups. The pigs in the LTBZ group had a higher villus height and villus height/crypt depth ratio when compared with other pigs. Moreover, the pigs in the LTBZ group exhibited higher mRNA expression levels of solute carrier family 39 and lower expression levels of solute carrier family 30 than those fed the HTBZ-supplemented diet. Together, these results indicate that TBZ may potentially be used as a dietary zinc source for young growing pigs and that dietary supplementation with LTBZ benefits growth performance and gut morphology.

Combining Network Pharmacology with Experimental Validation to Elucidate the Mechanism of Salvianolic Acid B in Treating Diabetic Peripheral Neuropathy.

Background: Salvianolic acid B (Sal B) is a bioactive component of Radix Salviae, which has antiinflammation and antiapoptotic activity in diabetic complications. However, the molecular mechanism of action of Sal B on diabetic peripheral neuropathy (DPN) is unknown. This study was designed to identify a mechanism for Sal B in the treatment of DPN by using a pharmacology network, molecular docking, and in vitro experiments. Methods: Sal B and DPN-related targets from Gene Cards and OMIM platforms were retrieved and screened. Then, an analysis of possible targets with STRING and Cytoscape software was conducted. KEGG signaling pathways were determined using the R software. Subsequently, the binding capacity of Sal B to target proteins was analyzed by molecular docking and in vitro experiments. Results: A total of 501 targets related to Sal B and 4662 targets related to DPN were identified. Among these targets, 108 intersection targets were shared by Sal B and DPN. After topological and cluster analysis, 11 critical targets were identified, including p38MAPK. KEGG analysis revealed that the AGE-RAGE signaling pathway likely plays an important role in Sal B action on DPN. The p38MAPK protein is a key target in the AGE-RAGE signaling pathway. Molecular docking results suggested that Sal B and p38MAPK have excellent binding affinity (<-5 kcal/mol). The in vitro experiments revealed that Sal B downregulates the expressions of p-P38MAPK, inflammatory cytokines, and apoptosis targets, which are upregulated by hyperglycemia. Conclusion: Sal B may alter DPN by inhibiting inflammation and apoptosis activated by p38MAPK.

Risk Factors of Urinary Pathogenic Bacteria Infection after Benign Prostatic Hyperplasia Surgery and Curative Effect Analysis of Shuangdong Capsule Intervention.

Benign prostatic hyperplasia (BPH) is a common and frequently occurring disease in clinics, with the main manifestations including frequent micturition, urinary incontinence, dysuria, and endless urination. Transurethral resection of the prostate (TURP) is the main treatment for BPH, but some patients are prone to urinary tract infection after surgery, which affects the prognosis. Therefore, it is of great significance to study the pathogenic characteristics and risk factors of postoperative urinary-derived pathogenic bacteria infection in patients with BPH for the prevention and treatment of postoperative infection. In addition, the treatment of patients with this disease is also the focus of clinical attention. Long-term massive application of antibiotics can induce drug-resistant mutations of bacteria, so it is urgent to find an efficient and safe therapeutic scheme in clinics. However, traditional Chinese medicine (TCM) has a long history of treating urinary tract infections. Therefore, Shuangdong capsule, a traditional Chinese medicine preparation, was selected for the combined treatment in this study. The results showed that age, concomitant diabetes mellitus, and preoperative prophylactic application of antibiotics were the independent risk factors for postoperative urine-derived pathogenic infection in BPH patients. Clinical intervention for BPH patients with concomitant risk factors should be emphasized in clinical practice. The combined use of Shuangdong capsule and conventional western medicine can improve the clinical symptoms and inflammatory reactions of postoperative urine-derived pathogenic infection in BPH patients. Due to its exact curative effect and high safety, it is worthy of promotion. The clinical study registration number is M2022019.

Identification of JUN as determinant of osteoarthritis and its inhibition by the Chinese herbal formulae Zhuanggu Huoxue Tang.

Synovitis is an essential feature of Osteoarthritis (OA). Increasing evidence demonstrates that synovitis plays a critical role in OA's symptoms and structural progression. However, there is no effective drug for preventing and treating synovitis. Some Chinese herbal formulae have been found to treat clinical OA effectively, however, their mode of action is still unclear. This study investigated the Chinese herbal formulae Zhuanggu Huoxue Tang (ZHT) underlying mechanisms for treating osteoarthritis. Transcriptome data and a network pharmacology analysis were used to investigate the biochemical pathways affected by ZHT during OA treatment with in vitro verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were undertaken. The interaction network of the ZHT active constituent targets was determined using Cytoscape 3.7.1 software. Molecular docking of key pathogenic proteins and components of ZHT was performed in silico to confirm the compounds' pharmaceutical activities. The results establish that JUN is a target pathway in the pathogenesis of osteoarthritis. Miltirone, one of the active ingredients of ZHT, demonstrated a suitable binding activity with JUN. Miltirone alleviates the catabolic gene expression induced by IL-1ß and IL-6 in synovial fibroblasts (FLS), validating the use of Miltirone as a therapeutic drug for osteoarthritis.

Baihe Extracts Reduce the Activation and Apoptosis of Microglia in the Hippocampus of Mice with Depression-like Behaviors by Downregulating MYC.

The purpose of our investigation is to identify the potential effects and key molecular targets of Baihe extracts in depression treatment. Network meta-analysis was applied for the synthesis of efficacy outcomes of fluoxetine and three traditional Chinese medicine Baihe prescriptions in depression. Depression-related target genes were screened using "GeneCards" database and "Comparative Toxicogenomics Database (CTD)". The major active components and targets of Baihe were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The identified depression-related genes and the target genes of Baihe were intersected, an interaction network was constructed using the "String" database, and key target genes were determined based on their degree value. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) profiles was performed using the "ClusterProfiler" R package. A mouse model with depression-like behaviors was constructed to verify the putative roles of the in silico identified key genes. Microglia were isolated from the mouse hippocampus, and the effects of Baihe extract-containing serum on microglia activation and apoptosis by targeting the key genes were examined in vitro. The meta-analysis results revealed no obvious differences in depression treatment efficacy between fluoxetine and the three Baihe prescriptions, suggesting Baihe extracts as a safe and effective alternative treatment for depression. Using network pharmacology and bioinformatics analysis, Baihe extracts were found to modulate depression by regulating 15 key genes, with MYC as the key gene. Subsequent animal experiments demonstrated that Baihe extracts reduced depression-related behavior, microglial activation, and inflammatory mediator release in mice by inhibiting MYC. Serum containing Baihe extracts could inhibit the activation of microglia and the release of inflammatory mediators by downregulating MYC. In summary, Baihe extracts were found to diminish MYC expression to reduce microglial activation and inflammatory factor release, thereby exerting antidepressant effects.

Attenuation of Oxidative Stress-Induced Cell Apoptosis and Pyroptosis in RSC96 Cells by Salvianolic Acid B.

OBJECTIVE: To determine whether salvianolic acid B (Sal B) exerts protective effects on diabetic peripheral neuropathy by attenuating apoptosis and pyroptosis. METHODS: RSC96 cells were primarily cultured with DMEM (5.6 mmol/L glucose), hyperglycemia (HG, 125 mmol/L glucose) and Sal B (0.1, 1, and 10 µ mol/L). Cells proliferation was measured by 3-(4, 5-cimethylthiazol-2-yl)-2, 5-dilphenyltetrazolium bromide assay. Reactive oxygen species (ROS) generation and apoptosis rate were detected by flow cytometry analysis. Western blot was performed to analyze the expressions of poly ADP-ribose polymerase (PARP), cleaved-caspase 3, cleaved-caspase 9, Bcl-2, Bax, NLRP3, ASC, and interleukin (IL)-1ß. RESULTS: Treatment with HG at a concentration of 125 mmol/L attenuated cellular proliferation, while Sal B alleviated this injury (P<0.05). In addition, Sal B inhibited HG-induced ROS production and apoptosis rate (P<0.05). Furthermore, treatment with Sal B down-regulated HG-induced PARP, cleaved-caspase 3, cleaved-caspase 9, Bax, NLRP3, ASC, and IL-1ß expression, but mitigated HG-mediated down-regulation of Bcl-2 expression (P<0.05). CONCLUSION: Sal B may protect RSC96 cells against HG-induced cellular injury via the inhibition of apoptosis and pyroptosis activated by ROS.

Serine Supplementation in the Diets of Late Gestating and Lactating Sows Improves Selenium Nutritional Status in Sows and Their Offspring.

Serine can regulate selenoprotein expression, and dietary serine is correlated with the contents of plasma selenoprotein P (Sepp1) and milk selenium (Se) in lactating mothers. Based on this, we investigated the effects of serine supplementation in the diets of late gestating and lactating sows on Sepp1 and Se contents in sows and their offspring. A total of 72 sows were assigned to four groups. During the experiment, sows were fed either a basal diet or basal diets supplemented with three different levels of serine. The results showed that maternal dietary serine had no effect on the Se content in the serum of sows and their offspring, whereas it significantly increased the Se content in the liver of piglets at the age of 21 days. Maternal dietary serine significantly increased Sepp1 content, either in the serum of sows or that in their offspring at the ages of 3 days, 7 days, and 21 days. Additionally, maternal dietary serine significantly increased litter weight and the average body weight of piglets at the age of 11 days. Notably, a positive correlation was found between the average body weight of piglets at the age of 11 days and serum Sepp1 content in piglets, at the age of either 3 days or 7 days. In conclusion, maternal dietary serine supplementation could improve Se nutritional status in sows and their offspring. These beneficial changes may contribute to the higher body weight of the offspring.

The Adjuvant Effects on Vaccine and the Immunomodulatory Mechanisms of Polysaccharides From Traditional Chinese Medicine.

Vaccination is still the most successful strategy to prevent and control the spread of infectious diseases by generating an adequate protective immune response. However, vaccines composed of antigens alone can only stimulate weak immunogenicity to prevent infection in many cases. Adjuvant can enhance the immunogenicity of the antigens. Therefore, adjuvant is urgently needed to strengthen the immune response of the vaccines. An ideal adjuvant should be safe, cheap, biodegradable and biologically inert. In addition to having a long shelf life, it can also promote cellular and humoral immune responses. Traditional Chinese medicine (TCM) has many different ingredients, such as glycosides, polysaccharides, acids, terpenes, polyphenols, flavonoids, alkaloids, and so on. TCM polysaccharides are one of the main types of biologically active substances. They have a large range of pharmacological activities, especially immunomodulatory. TCM polysaccharides can regulate the immune system of animals by binding to multiple receptors on the surface of immune cells and activating different signal pathways. This review focuses on a comprehensive summary of the most recent developments in vaccine adjuvant effects of polysaccharides from many important TCM, such as Artemisia rupestris L., Cistanche deserticola, Pinus massoniana, Chuanminshen violaceum, Astragalus, Ganoderma lucidum, Codonopsis pilosula, Lycium barbarum, Angelica, Epimedium, and Achyranthes bidentata. Moreover, this review also introduces their immunomodulatory effects and the molecular mechanisms of action on animal bodies, which showed that TCM polysaccharides can activate macrophages, the signal pathway of T/B lymphocytes, regulate the signal pathway of natural killer cells, activate the complement system, and so on.

Dietary Serine Supplementation Regulates Selenoprotein Transcription and Selenoenzyme Activity in Pigs.

The synthesis of selenocysteine and its incorporation into selenoproteins require serine during the action of seryl-tRNA synthetase. In view of this, we conducted this study to explore the effects of dietary serine supplementation on selenoprotein transcription and selenoenzyme activity in pigs. A total of 35 crossbred barrows (28 days old) were randomly assigned to five treatment groups. During the 42-day growth experiment, pigs were fed either a basal diet with no supplemented serine or diets supplemented with 0.25%, 0.5%, 0.75%, or 1% serine. The results showed that serine supplementation had no effect on the selenium content in the serum, skeletal muscle, and kidney of pigs. However, dietary supplementation with 0.5% serine significantly increased the selenium content in the liver. Diets supplemented with different levels of serine significantly increased the gene expression of glutathione peroxidase 1 (Gpx1), Gpx2, thioredoxin reductase 1 (Txnrd1), Txnrd2, and selenoprotein P (Sepp1) in the skeletal muscle and liver of pigs. Moreover, pigs supplemented with 0.5% serine had the highest selenoprotein P concentration and glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) activities in the skeletal muscle, which were significantly higher than those in the control pigs. Additionally, pigs supplemented with 0.25% serine had the highest GPx and TrxR activities in the liver, which were significantly higher than those in the control pigs. In conclusion, dietary serine supplementation could improve selenoprotein transcription and selenoenzyme activity in pigs, with the appropriate concentrations of serine to be included in the diet being 0.25% or 0.5%.

Improved cancer phototheranostic efficacy of hydrophobic IR780 via parenteral route by association with tetrahedral nanostructured DNA.

As a photosensitizer with effective photothermal (PTT) and photodynamic (PDT) response, IR780 has been widely explored as promising cancer phototheranostic molecule. However, the systematic administration of IR780 usually suffers from poor water solubility and low photostability, so that it cannot be administrated by parenteral route. In this study, we design a tetrahedral DNA (Td)-based nanosystem to load IR780 (IR780@Td) via electrostatic interaction and π-π stacking. After encapsulation, the water solubility and photostability of IR780 have been greatly improved, and the IR780@Td shows an appropriate nanoformulated size (224 nm) to facilitate hyperthermia-mediated tumor targeting by EPR effect. The nanostructure of Td is proved to be crucial for the proper size and good stability of IR780@Td nanoformulation for in vivo application. The in vitro and ex vivo PTT/PDT efficiencies of IR780 are improved in IR780@Td group. In the tumor-bearing mice, the accumulation of IR780 in tumor site is significantly high in IR780@Td group. Under near-infrared laser irradiation, the intravenous administration of IR780@Td promotes the tumor imaging and enhances anti-tumor effect than IR780 treatment. In summary, the proposed strategy shows promising effect in facilitating intravenous injection of IR780 and enhancing the phototheranostic efficacy for cancer treatment.

Maternal serine supply from late pregnancy to lactation improves offspring performance through modulation of metabolic pathways.

Maternal dietary serine affects free amino acid content in milk and the antioxidant ability of progeny. However, whether maternal dietary serine has any effects on offspring performance in pigs and related metabolic consequences remains unknown. This study was conducted to investigate the effects of different levels of maternal dietary serine from late pregnancy to lactation on sow reproductive performance and offspring performance, and on the metabolome of milk and the serum of sows and their offspring. The results showed that sows fed a diet supplemented with 25% serine of the basal diet (l-Ser) had a higher litter weight, and higher average piglet weight at birth and aged 21 days when compared with sows fed the basal diet (CON). We found a large number of metabolites in both colostrum and milk that differed significantly between sows in the CON and l-Ser groups. Additionally, twenty metabolites differed in the serum of piglets aged 21 days between the CON and l-Ser groups. Most of these metabolites are involved in purine and pyrimidine metabolism, glutathione and taurine metabolism, as well as phospholipid and sphingolipid metabolism, which may contribute to the growth-promoting effects of serine on offspring. Our results imply that maternal serine has the potential to improve offspring outcomes.

Astragalosideâ £ against cardiac fibrosis by inhibiting TRPM7 channel.

BACKGROUND: Astragaloside Ⅳ (ASG-Ⅳ, (Fig. 1) is the most active component of Chinese sp. Astragalus membranaceus Bunge (Fabaceae) that has showed antioxidant, antiapoptotic and antiviral activities among others. It is reported to play an important role in cardiac fibrosis (CF), but the mechanism remains unclear. PURPOSE: To investigate the mechanism of ASG-Ⅳ on inhibiting myocardial fibrosis induced by hypoxia. STUDY DESIGN: We studied the relationship between anti-fibrotic effect of ASG-Ⅳ and transient receptor potential cation channel, subfamily M, member 7 (TRPM7) by in vivo and in vitro experiments. METHODS: In vivo, CF was induced by subcutaneous isoproterenol (ISO) for 10 days. Rat hearts were resected for histological experiment and reverse transcription real-time quantitative poly merase chain reaction (RT-qPCR). In vitro, molecular and cellular biology technologies were used to confirm the anti-fibrosis effect underlying mechanism of ASG-Ⅳ. RESULTS: Histological findings and the collagen volume fraction showed that ASG-Ⅳ decreased fibrosis in heart tissues. Hypoxia could stimulate the proliferation and differentiation of cardiac fibroblast which indicated that the degree of fibrosis was increased significantly. Anoxic treatment could also obviously up-regulate the expression of TRPM7 protein and current. ASG-Ⅳ groups showed the opposite results. Knock-down TRPM7 experiment further confirmed the role of TRPM7 channel in hypoxia-induced cardiac fibrosis. CONCLUSION: Our results suggest that the inhibition of hypoxia-induced CF in vivo and in vitro by ASG-IV is associated with reduction of the expression of TRPM7. The moderate inhibition of the TRPM7 channel may be a new strategy for treating cardiac fibrosis.

Puerarin may protect against Schwann cell damage induced by glucose fluctuation.

Puerarin is one of the major active ingredients in Gegen, a traditional Chinese herb that has been reported to have a wide variety of beneficial pharmacology functions. Previous studies have implicated that the damaging effects of hyperglycemia resulting from oxidative stress and glucose fluctuation may be more dangerous than constant high glucose in the development of diabetes-related complications. The present study focuses on the effects of puerarin on glucose fluctuation-induced oxidative stress-induced Schwann cell (SC) apoptosis in vitro. Primarily cultured SCs were exposed to different conditions and the effect of puerarin on cell viability was determined by MTT assays. Intracellular reactive oxygen species (ROS) generation and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by the Annexin V-FITC/PI and TUNEL method. Quantitative real-time reverse transcriptase polymerase chain reaction was performed to analyze the expression levels of bax and bcl-2. Western blot was performed to analyze the expression levels of some important transcription factors and proteins. The results showed that incubating SCs with intermittent high glucose for 48 h decreased cell viability and increased the number of apoptotic cells whereas treating with puerarin protected SCs against glucose fluctuation-induced cell damage. Further study demonstrated that puerarin suppressed activation of apoptosis-related proteins including PARP and caspase-3, downregulation of bcl-2, and upregulation of intracellular distribution of bax from cytosol to mitochondria, which was induced by glucose fluctuation. Moreover, puerarin inhibited the elevation of intracellular ROS and mitochondrial depolarization induced by glucose fluctuation. These results suggest that puerarin may protect SCs against glucose fluctuation-induced cell injury through inhibiting apoptosis as well as oxidative stress.

Ginsenoside Rb1 prevents high glucose-induced Schwann cell injury through the mitochondrial apoptosis pathway.

OBJECTIVE: To investigate the effects of ginsenoside Rb1 on high glucose-induced neurotoxicity and the underlying molecular mechanism in primary cultured Schwann cells (SCs). METHODS: Cultured SCs were divided into six groups that received (a) normal glucose, (b) osmotic control, (c) high glucose, (d) high glucose plus 1 µM ginsenoside Rb1, (e) high glucose plus 10 µM ginsenoside Rb1, or (f) high glucose plus 100 µM alpha lipoic acid (ALA). Intracellular reactive oxygen species (ROS) generation and mitochondrial transmembrane potential (ΔΨm) were detected by flow cytometric analyses. Apoptosis was confirmed by the annexin V-FITC/propidium iodide (PI) method, and the concentration of 8-hydroxy-2-deoxy guanosine (8-OHdG) was detected by an enzyme-linked immunosorbent assay. Western blotting was performed to analyze the expression levels of important transcription factors such as cytochrome c, bcl-2, bax, activated caspase-3, and activated poly (ADP-ribose) polymerase (PARP). RESULTS: Ginsenoside Rb1 inhibited high glucose-induced oxidative stress by decreasing ROS and 8-OHdG levels as well as mitochondrial depolarization in SCs. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide and annexin V-FITC/PI assays showed that incubating SCs with high glucose decreased cell viability and increased the number of apoptotic cells, whereas treatment with ginsenoside Rb1 protected SCs against high glucose-induced cell damage. Furthermore, ginsenoside Rb1 down-regulated the expression of high glucose-induced bax and cytochrome c release but up-regulated bcl-2 expression. In addition, ginsenoside Rb1 attenuated high glucose-induced activation of caspase-3 and minimized cleavage of PARP in SCs. CONCLUSION: These results suggest that ginsenoside Rb1 antagonizes high glucose-induced oxidative stress and activation of the mitochondrial apoptosis pathway in SCs.

Qualitative analysis of major constituents from Xue Fu Zhu Yu Decoction using ultra high performance liquid chromatography with hybrid ion trap time-of-flight mass spectrometry.

Xue Fu Zhu Yu Decoction, a famous formula that has been used for treating many blood stasis-caused diseases for many centuries, comprises 11 kinds of traditional Chinese medicines. A convenient, efficient, and rapid analytical method was developed to simultaneously determine the major compounds in this decoction. An ultra-high performance liquid chromatography with hybrid ion trap time-of-flight mass spectrometry method was used to rapidly separate and detect the major constituents of the decoction. Using this technique, we identified or tentatively identified 34 compounds, including 21 flavonoids, 5 terpenoids, 3 organic acids, 2 lactones, 1 alkaloid, 1 amino acid, and 1 cyanogenic glycoside. The MS analysis of these constituents was described in detail. Findings may contribute to future metabolic and pharmacokinetic studies of this medicine.

Novel alternative therapy for spinal tuberculosis during surgery: reconstructing with anti-tuberculosis bioactivity implants.

Accompanied with the worsening of the pulmonary tuberculosis bacterium (TB) epidemic, the incidence of spinal TB has increased in recent years. Spinal reconstruction and stabilisation, and bone defect repair play a crucial role in the surgical treatment of spinal TB. Unfortunately, the existing materials have not completely met the requirements for spinal TB reconstruction due to their diverse deficiencies. Therefore, there is an urgent need to develop novel reconstructing implants. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite (nHA) are two promising drug delivery systems (DDS) and materials for bone repair, which could help us to overcome the difficulties in spinal TB reconstruction in the future. In this article, we discuss the properties of PDLLA and nHA, two potential drug delivering and bone repair materials for spinal TB reconstruction. We also presented two alternatives for spinal TB in future. Two strategies have the potential for treating spinal TB in the future. One such strategy consists of mixing anti-TB drugs, PDLLA with nHA to fabricate a novel three-dimensional (3D) porous scaffold via 3D printing (3DP) technology. Another is preparing a novel titanium mesh implant coated with drugs/PDLLA/nHA composites by solvent evaporation and low-temperature drying technology. These two hypotheses have recently been tested in a laboratory setting by our team.