The clinical efficacy of Shenxiang Suhe Pill administration in posterior circulation ischemic vertigo: A randomized controlled trial.

BACKGROUND: Shenxiang Suhe Pill (SXSHP) is a traditional Chinese medicine (TCM) widely used to treat coronary heart disease. The present study aims to investigate the effect of SXSHP on posterior circulation ischemic (PCI) vertigo. METHODS: One hundred and twenty patients with PCI vertigo were randomly divided into the control, low-dose, and high-dose groups with 40 patients in each group. The control group was treated with basic Western medicine. The low-dose and high-dose groups were treated with 0.7 g SXSHP once a day in the morning and twice a day in the morning and evening, respectively. The assessments were performed on days 14 and 28. The traditional Chinese medicine symptom score, average blood flow velocity of vertebral artery and basilar artery, blood viscosity, blood lipids, serum C-reactive protein level (CRP), blood routine test, and liver and kidney function were compared before and after treatment among the 3 groups. RESULTS: In the evaluation of the traditional Chinese medicine symptom score, both low-dose and high-dose SXSHP treatments showed higher efficacy than the control group (P = .013). The average blood flow velocity of vertebral artery and basilar artery in the 3 groups showed an upward trend from baseline (P < .05). The blood viscosity and levels of fibrinogen, hematocrit, and CRP in the 3 groups showed a downward trend from baseline level (P < .05). The levels of total cholesterol, triglycerides, low-density lipoprotein, and CRP in the low-dose group and high-dose group were lower than those in the control group on day 28 (P < .05). There were no significant differences in the routine blood test and liver and kidney function between the low-dose and high-dose groups compared with the baseline values (P > .05). CONCLUSION: SXSHP effectively improved PCI vertigo by inhibiting blood viscosity, regulating blood lipid levels, anti-inflammation, and improving cerebrovascular blood flow without affecting liver and kidney functions.

Behavior and physiology in female Cricetulus barabensis are associated with the expression of circadian genes.

The circadian clock regulates the behavior, physiology, and metabolism of mammals, and these characteristics, such as sleep-wake cycles, exercise capacity, and hormone levels, exhibit circadian rhythms. Light signaling is the main stimulator of the mammalian circadian system. The photoperiod regulates the reproductive cycle of seasonal breeding animals, and the circadian clock plays a pivotal role in this process. However, the role of the clock in coordinating animal behavior and physiology in response to photoperiodic changes needs further investigation. The present study investigated the changes and correlation of behavioral activities, physiological indicators, and gene expression in female striped hamsters (Cricetulus barabensis) within 24 h under a 12L:12D photoperiod. We found that the daily rhythms of sleep-wake and open field were significant in hamsters. The expression of clock genes, melatonin receptor genes, and genes involved in general metabolism oscillated significantly in central and peripheral tissues (brain, hypothalamus, liver, ovary, and thymus) and was significantly associated with behavior and physiology. Our results revealed that the neuroendocrine system regulated the rhythmicity of behavior and physiology, and central and peripheral clock genes (Bmal1, Clock, Per1, Per2, Cry1, and Cry2), melatonin receptor genes (MT1, MT2, and GPR50), and metabolizing genes (SIRT1, FGF21, and PPARα) played important roles. Our results suggest that central and peripheral circadian clocks, melatonin receptors, and genes involved in general metabolism may play key roles in maintaining circadian behavior and metabolic homeostasis in striped hamsters. Our results may have important implication for rodent pest control.

Preparation of flexible and UV-blocking films from lignin-containing cellulose incorporated with tea polyphenol/citric acid.

Lignin-containing bamboo cellulose, fractionated from a pilot-scale microwave liquefaction of bamboo was dissolved in tetrabutylammonium acetate/dimethyl sulfoxide (TBAA/DMSO) for the fabrication of highly flexible, transparent and UV-blocking films. Tea polyphenol (TP) or citric acid (CA) was added during the dissolving process in order to modify the film's properties. The results showed that the addition of TP obviously improved the elongation at break (triple that of the control) and UV-blocking ability of the films. Both the addition of TP and CA could increase the water contact angle of the films. The films incorporated with TP and CA were much more thermal stable than previously reported similar films. The proposed film fabrication mechanism revealed that stable hydrogen bonds formed between the lignin-cellulose matrix and TP/CA, resulting in the enhancement on the properties of the films. This present study showed that lignin-containing cellulose with the incorporation of TP/CA had great potential in the preparation of films in place of plastic.

Astragali Radix-Coptis Rhizoma Herb Pair Attenuates Atherosclerosis in ApoE-/- Mice by Regulating the M1/M2 and Th1/Th2 Immune Balance and Activating the STAT6 Signaling Pathway.

OBJECTIVE: Immune imbalance and the inflammatory response are associated with atherosclerosis (AS) progression. Astragali Radix and Coptis Rhizoma (ARCR) are an ancient and classic herb pair that is used in herbal medicines for the treatment of coronary heart disease. We focused on the effects and mechanisms of the ARCR herb pair attenuation of atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice. METHODS: ApoE-/- mice were fed a high-fat diet for 12 weeks to establish a model of AS. The ApoE-/- mice were randomly divided into a model group, simvastatin group (Simva), Astragali Radix group (AR), Coptis Rhizoma group (CR), Astragali Radix-Coptis Rhizoma group (ARCR), and Astragali Radix-Coptis Rhizoma + signal transducer and activator of transcription factor 6 (STAT6) inhibitor (AS1517499) group (ARCR + AS1517499). C57BL/6 mice were used as controls. Each group was administered the corresponding drugs, and mice in the model and control groups were given the same volume of normal saline once daily for 6 weeks. The body weights of the mice were observed regularly. The effect of the ARCR herb pair on lipid content in peripheral blood was evaluated using blood lipid tests. The levels of serum matrix metalloproteinase-9 (MMP-9), interleukins-12 (IL-12), IL-10, interferon-γ (IFN-γ), and IL-4 were determined to assess inflammation. Oil Red O staining, Sirius Red staining, and immunohistochemistry were used to observe changes in plaque stability. Western blotting was used to assay M1/M2 macrophages, Th1/Th2 cells, and STAT6 signaling pathway protein expression. Flow cytometry and immunofluorescence were used to detect M1/M2 macrophages and Th1/Th2 cells and reflect the immune imbalance. RESULTS: The ARCR herb pair significantly reduced blood lipids levels and plaque vulnerability and regulated the levels of inflammatory factors and the number of M1/M2 macrophages and Th1/Th2 cells in ApoE-/- AS mice. It also decreased iNOS and T-bet protein levels and increased the Arg-1 and GATA-3 protein levels. The ARCR herb pair also increased STAT6 phosphorylation. A STAT6 inhibitor attenuated the regulation of M1/M2 and Th1/Th2 markers induced by the ARCR herb pair. CONCLUSION: The ARCR herb pair regulates blood lipid metabolism and attenuates atherosclerosis via regulation of M1/M2 and Th1/Th2 immune balance, which is achieved partially by increasing STAT6 phosphorylation. Our study provides new evidence for the possible use of ARCR herb pair in the prevention and treatment of AS.

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model.

BACKGROUND: Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. METHODS: The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. RESULTS: A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1ß, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1ß, MMP-2 and MMP-9 in rats. CONCLUSION: The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-fluorouracil on gastric cancer cells through the AKT-mTOR pathway.

BACKGROUND: Gastric cancer is one of the most common and deadly malignancies worldwide. Despite recent medical progress, the 5-year survival rate of gastric cancer is still unsatisfactory. 5-fluorouracil (5-Fu) is one of the first-line antineoplastic treatments for gastric cancer, as it can effectively induce cancer cell apoptosis. However, the effect of 5-Fu is limited due to drug resistance of the malignant tumor. Previous studies have reported that Sotetsuflavone from Cycas revoluta Thunb. can markedly suppress lung cancer cell proliferation by apoptosis, though its effect on gastric cancer remains unknown. AIM: To investigate the inhibitory effect of Cycas revoluta Thunb. and to determine whether it can overcome gastric cancer cell drug resistance to 5-Fu. METHODS: Cell viability was examined to determine whether the natural extract of Cycas revoluta Thunb. induced gastric cancer cell death. The half-maximal effective concentration and the half-maximal lethal concentration were calculatede. Wound-healing and transwell assays were performed to examine gastric cancer cell motility. Clonogenic assays were performed to investigate the synergistic effects of Cycas revoluta Thunb. with 5-Fu, and apoptotic bodies were detected by Hoechst staining. Western blotting was performed to examine the expression of related proteins and to investigate the molecular mechanism of Cycas revoluta Thunb.-induced cancer cell apoptosis. The expressions of proteins, including mammalian target of rapamycin (mTOR) and p-AKT, were detected in different combinations of treatments for 48 h, then analyzed by ECL detection. RESULTS: Gastric cancer cells were more sensitive to the natural extract of Cycas revoluta Thunb. compared to normal gastric epithelial cells, and the extract effectively inhibited gastric cancer cell migration and invasion. The extract improved the anti-cancer effect of 5-Fu by enhancing the chemosensitization of gastric cancer cells. Extract plus 5-Fu further reduced the expression of the drug-resistance-related proteins p-AKT and mTOR after 48 h compared to 5-Fu alone. Compared to 5-Fu treatment alone, mTOR and p-AKT expression was significantly reduced by about 50% and 75%, respectively. We also found that the natural extract of Cycas revoluta Thunb. further increased 5-Fu-induced gastric cancer cell apoptosis. Expression of apoptosis-related protein X-linked inhibitor of apoptosis protein and apoptosis inducing factor were significantly reduced and increased, respectively, in the 5-Fu-resistant gastric cancer line SGC-7901/R treated with extract plus 5-Fu, while the expression of survivin did not change. CONCLUSION: The natural extract of Cycas revoluta Thunb. effectively inhibited gastric cancer cell growth and enhanced the anti-cancer effect of 5-Fu through the AKT-mTOR pathway.

Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2.

The carnitine shuttle system (CSS) plays a crucial role in the transportation of fatty acyls during fatty acid ß-oxidation for energy supplementation, especially in cases of high energy demand, such as in cancer. In this study, to systematically characterize alterations of the CSS in hepatocellular carcinoma (HCC), acylcarnitine metabolic profiling was carried out on 80 pairs of HCC tissues and adjacent noncancerous tissues (ANTs) by using ultra-performance liquid chromatography coupled to mass spectrometry. Twenty-four acylcarnitines classified into five categories were identified and characterized between HCCs and ANTs. Notably, increased saturated long-chain acylcarnitines (LCACs) and decreased short- and medium-chain acylcarnitines (S/MCACs) were simultaneously observed in HCC samples. Subsequent correlation network and heatmap analysis indicated low correlations between LCACs and S/MCACs. The mRNA and protein expressions of carnitine palmitoyltransferase 2 (CPT2) was significantly downregulated in HCC samples, whereas CPT1A expression was not significantly changed. Correspondingly, the relative levels of S/MCACs were reduced and those of LCACs were increased in BEL-7402/CPT2-knockdown cells compared to negative controls. Both results suggested that decreased shuttling efficiency in HCC might be associated with downregulation of CPT2. In addition, decreases in the mRNA expression of acetyl-CoA acyltransferase 2 were also observed in HCC tissues and BEL-7402/CPT2-knockdown cells, suggesting potential low ß-oxidation efficiency, which was consistent with the increased expression of stearoyl-CoA desaturase 1 in both samples. The systematic strategy applied in our study illustrated decreased shuttling efficiency of the carnitine shuttle system in HCC and can provide biologists with an in-depth understanding of ß-oxidation in HCC.

[The synergistic and toxicity-reducing effects of zhenqifuzheng injection on mice with 60Co radiotherapy].

OBJECTIVE: To study the synergistic and toxicity-reducing effect of zhenqifuzheng (ZQFZ) injection on mice with 60Co radiotherapy. METHODS: The tumor-bearing mice models with Hepatoma-22 were established. Mice in 60Co control group were treated by 60Co; ZQFZ injection were administered with dosages of 1.5, 3.0, 6.0 g/(kg x d) through ip for 7 days,then the inhibitory rate, the number of WBC,the spleen and thymus index were calculated. Meanwhile,the MDA content and SOD activity in serum were determined. Phagocytosis of mononuclear macrophage was determined with carbon particle clearance test. RESULTS: Each dose of ZQFZ injection inhibited the development of tumor, and had synergism with 60Co. High dose of ZQFZ injection increased the number of WBC, and the spleen index in all ZQFZ groups increased (P < 0.05 or P < 0.01). Whereas, no significant difference was found of thymus index in all groups, and the changes of MDA content and SOD activity induced by 60Co were reversed obviously by three doses of ZQFZ (P < 0.05 or P < 0.01). Meanwhile, non-specific immunity was enhanced in different degree in three doses of ZQFZ groups (P < 0.01). CONCLUSION: ZQFZ injection can increase the activity of non-specific immunity, improve the anti-tumor effects and meanwhile attenuate the toxicity of 60Co, which may be related to the antagonistic effect on lipid peroxidation.