Combined Effect of Early Physical Exercise and Stereotactic Hematoma Evacuation in Patients with Cerebral Hemorrhage Undergoing Hemodialysis.

Objective: This study investigated the combined effect of stereotactic hematoma evacuation and early postoperative physical function exercise in hemodialysis patients with cerebral hemorrhage. Methods: A retrospective study was conducted, including a total of 78 hemodialysis patients with cerebral hemorrhage treated at our hospital between January 2021 and June 2022. The patients were equally allocated to two groups based on different postoperative rehabilitation methods. The control group underwent stereotactic hematoma evacuation, while the study group received additional early postoperative physical function exercise in addition to the intervention provided to the control group. The operative conditions of both groups were recorded, and comparisons were made concerning neural function, limb function, daily activity ability, and complications. Results: There were no significant differences between the two groups regarding operation time, intraoperative blood loss, and hematoma removal rate (P > .05). However, the study group demonstrated a significantly shorter hospital stay (12.98 ± 2.01 days) compared to the control group (15.02 ± 2.07 days), P < .05. Post-treatment, the study group exhibited substantially lower neurological function scores (NIHSS score) (6.37 ± 1.02) compared to the control group (10.03 ± 1.09), P < .05. Additionally, the study group showed significantly higher limb function scores (P < .05) and daily activity ability scores (P < .05) compared to the control group. Moreover, the incidence of complications in the study group was significantly lower than that in the control group (P < .05). Conclusions: Early postoperative physical function exercise following stereotactic hematoma evacuation showed beneficial effects in hemodialysis patients with cerebral hemorrhage. It effectively reduced operation time, restored nerve and limb function, improved daily activity ability, and reduced the incidence of related complications. These approaches hold crucial clinical significance.

(5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART: a randomized, double-blinded, placebo-controlled phase II study.

Background: Therapeutic approaches to HIV-suppressed immunological non-responders (INRs) remain unsettled. We previously reported efficacy of Chinese herbal Tripterygium wilfordii Hook F in INRs. Its derivative (5R)-5-hydroxytriptolide (LLDT-8) on CD4 T cell recovery was assessed. Methods: The phase II, double-blind, randomized, placebo-controlled trial was conducted in adults patients with long-term suppressed HIV infection and suboptimal CD4 recovery, at nine hospitals in China. The patients were 1:1:1 assigned to receive oral LLDT-8 0.5 mg or 1 mg daily, or placebo combined with antiretroviral therapy for 48 weeks. All study staff and participants were masked. The primary endpoints include change of CD4 T cell counts and inflammatory markers at week 48. This study is registered on ClinicalTrials.gov (NCT04084444) and Chinese Clinical Trial Register (CTR20191397). Findings: A total of 149 patients were enrolled from Aug 30, 2019 and randomly allocated to receiving LLDT-8 0.5 mg daily (LT8, n = 51), 1 mg daily (HT8, n = 46), or placebo (PL, n = 52). The median baseline CD4 count was 248 cells/mm3, comparable among three groups. LLDT-8 was well-tolerated in all participants. At 48 weeks, change of CD4 counts was 49 cells/mm3 in LT8 group (95% confidence interval [CI]: 30, 68), 63 cells/mm3 in HT8 group (95% CI: 41, 85), compared to 32 cells/mm3 in placebo group (95% CI: 13, 51). LLDT-8 1 mg daily significantly increased CD4 count compared to placebo (p = 0.036), especially in participants over 45 years. The mean change of serum interferon-γ-induced protein 10 was -72.1 mg/L (95% CI -97.7, -46.5) in HT8 group at 48 weeks, markedly decreased compared to -22.8 mg/L (95% CI -47.1, 1.5, p = 0.007) in placebo group. Treatment-emergent adverse events (TEAEs) were reported in 41 of 46 (89.1%) participants in HT8 group, 43 of 51 (84.3%) in LT8, and 42 of 52 (80.7%) in PL group. No drug-related SAEs were reported. Interpretation: LLDT-8 enhanced CD4 recovery and alleviated inflammation in long-term suppressed INRs, providing them a potential therapeutic option. Fundings: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, Shanghai Pharmaceuticals Holding Co., Ltd., and the National key technologies R&D program for the 13th five-year plan.

Catalpol rescues cognitive deficits by attenuating amyloid ß plaques and neuroinflammation.

This study sought to investigate the anti-amyloid ß (Aß) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model. METHODS: The effects of catalpol on Aß formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability. APPswe/PS1ΔE9 mice were treated with catalpol, and their cognitive ability was investigated using the water maze and novel object recognition tests. Immunohistochemistry and immunofluorescence were used to probe for protein markers of microglia and astrocyte, Aß deposits, and NF-κB pathway activity. Aß peptides, neuroinflammation, and nitric oxide production were examined using ELISA and redox reactions. RESULTS: Catalpol potently inhibited Aß fibril and oligomer formation. In microglial cells stimulated by Aß, catalpol alleviated the expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and inducible nitric oxide synthase (iNOS) but promoted the expression of the anti-inflammatory cytokine IL-10. Catalpol alleviated the cytotoxic effects of Aß-exposed microglia on HT22 cells. Treatment with catalpol in APPswe/PS1ΔE9 mice downregulated neuroinflammation production, decreased Aß deposits in the brains and alleviated cognitive impairment. Catalpol treatment decreased the number of IBA-positive microglia and GFAP-positive astrocytes and their activities of the NF-κB pathway in the hippocampus of APPswe/PS1ΔE9 mice. CONCLUSION: The administration of catalpol protected neurons by preventing neuroinflammation and Aß deposits in an AD mouse model. Therefore, catalpol may be a promising strategy for treating AD.

Water Extract of Chrysanthemum indicum L. Flower Inhibits Capsaicin-Induced Systemic Low-Grade Inflammation by Modulating Gut Microbiota and Short-Chain Fatty Acids.

Systemic low-grade inflammation induced by unhealthy diet has become a common health concern as it contributes to immune imbalance and induces chronic diseases, yet effective preventions and interventions are currently unavailable. The Chrysanthemum indicum L. flower (CIF) is a common herb with a strong anti-inflammatory effect in drug-induced models, based on the theory of "medicine and food homology". However, its effects and mechanisms in reducing food-induced systemic low-grade inflammation (FSLI) remain unclear. This study showed that CIF can reduce FSLI and represents a new strategy to intervene in chronic inflammatory diseases. In this study, we administered capsaicin to mice by gavage to establish a FSLI model. Then, three doses of CIF (7, 14, 28 g·kg-1·day-1) were tested as the intervention. Capsaicin was found to increase serum TNF-α levels, demonstrating a successful model induction. After a high dose of CIF intervention, serum levels of TNF-α and LPS were reduced by 62.8% and 77.44%. In addition, CIF increased the α diversity and number of OTUs in the gut microbiota, restored the abundance of Lactobacillus and increased the total content of SCFAs in the feces. In summary, CIF inhibits FSLI by modulating the gut microbiota, increasing SCFAs levels and inhibiting excessive LPS translocation into the blood. Our findings provided a theoretical support for using CIF in FSLI intervention.

Influence of CaO on Physical and Environmental Properties of Granulated Copper Slag: Melting Behavior, Grindability and Leaching Behavior.

Due to its potential pozzolanic activity, granulated copper slag (GCS) has been proven to act as a supplementary cementitious material (SCM) after thermochemical modification with CaO. This modification method reduces cement consumption and CO2 emissions; however, the additional energy consumption and environmental properties are also not negligible. This paper aims to evaluate the economics and environmental properties of thermochemically modified GCS with CaO through the melting temperature, grindability, and heavy metal leaching characteristics. The X-ray fluorescence spectroscopy (XRF) results indicated that the composition of the modified GCS shifted to the field close to that of class C fly ash (FA-C) in the CaO-SiO2-Al2O3 ternary phase diagram, demonstrating higher pozzolanic activity. The test results on melting behavior and grindability revealed that adding CaO in amounts ranging from 5 wt% to 20 wt% decreased the melting temperature while increasing the BET surface area, thus significantly improving the thermochemical modification's economics. The unconfined compressive strength (UCS) of the cement paste blended with 20 wt% CaO added to the modified GCS after curing reached 17.3, 33.6, and 42.9 MPa after curing for 7, 28, and 90 d, respectively. It even exceeded that of Portland cement paste at 28 d and 90 d curings. The leaching results of blended cement proved that the heavy metal elements showed different trends with increased CaO content in modified GCS, but none exceeded the limit values. This paper provides a valuable reference for evaluating thermochemically modified GCS's economics and environmental properties for use as SCM.

Xin-Ji-Er-Kang Alleviates Isoproterenol-Induced Myocardial Hypertrophy in Mice through the Nrf2/HO-1 Signaling Pathway.

Xin-Ji-Er-Kang (XJEK) inhibited cardiovascular remodeling in hypertensive mice in our previous studies. We hypothesized that XJEK may prevent isoproterenol (ISO)-induced myocardial hypertrophy (MH) in mice by ameliorating oxidative stress (OS) through a mechanism that may be related to the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) pathways. Forty SPF male Kunming mice were randomized into 5 groups (n = 8 mice per group): control group, MH group, MH + different doses of XJEK (7.5 g/kg/day and 10 g/kg/day), and MH + metoprolol (60 mg/kg/day). On the eighth day after drug treatment, electrocardiogram (ECG) and echocardiography were performed, the mice were sacrificed, and blood and heart tissues were collected for further analysis. XJEK administration markedly ameliorated cardiovascular remodeling (CR), as manifested by a decreased HW/BW ratio and CSA and less collagen deposition after MH. XJEK administration also improved MH, as evidenced by decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC) levels. XJEK also suppressed the decreased superoxide dismutase (SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) levels in serum of mice with MH. XJEK-induced oxidative stress may be related to potentiating Nrf2 nuclear translocation and HO-1 expression compared with the MH groups. XJEK ameliorates MH by activating the Nrf2/HO-1 signaling pathway, suggesting that XJEK is a potential treatment for MH.

Establishment of fingerprint and mechanism of anti-myocardial ischemic effect of Syringa pinnatifolia.

This study established the fingerprint of Syringa pinnatifolia Hemsl. (SP), analyzed the SP ingredients absorbed into the rats blood, and evaluated its anti-myocardial ischemic effect to provide a scientific basis for the follow-up development and research of SP and lay a foundation for its clinical application using ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS. Myocardial infarction was induced in rat by ligating the left anterior descending branch of the rat coronary artery, and SP alcohol extract was administered to evaluate its anti-myocardial ischemic effect. We analyzed the SP ingredients absorbed into the rats blood, screened the active compounds, established a database of SP anti-myocardial ischemic targets, and explored the possible mechanism of SP in treating myocardial infarction using bioinformatics. The rats were examined using echocardiography, serum biomarkers were determined, and pathological changes were observed by histopathological examination. TUNEL staining was performed to detect the apoptotic level of cells, and Western blot and quantitative real-time polymerase chain reaction were performed to detect the expression levels of Bcl-2, Bax, and Caspase-3 in heart tissues. In the fingerprint of SP, 24 common peaks were established, and the similarity evaluation results of 10 batches of SP were all >0.9. Ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS detected 17 active ingredients in the drug-containing serum, including terpenoids, flavonoids, phenols, phenylpropanoids, and phenolic acids, the most abundant of which was resveratrol. Enrichment analysis of SP targets against myocardial ischemia revealed that key candidate targets of SP were significantly enriched in multiple pathways associated with apoptosis. Resveratrol was administered to the successfully modeled rats, and the results showed that the resveratrol group significantly decreased left ventricular end-diastolic diameter and left ventricular end-systolic diameter and significantly increased ejection fraction and fractional shortening in all groups compared with the model group. Resveratrol significantly decreased the levels of creatine kinase isoenzyme and lactate dehydrogenase in serum compared to the model group (P < 0.001). Hematoxylin-eosin staining of rat myocardial tissue showed that all lesions were reduced under microscopic observation in the resveratrol group compared with the model group. Real-time polymerase chain reaction and Western blot results showed that the resveratrol group downregulated the expression of the proapoptotic factor Bax, upregulated the expression of the antiapoptotic factor Bcl-2, and decreased the expression of Caspase-3. The established fingerprints are accurate, reliable, and reproducible and can be used as an effective method for quality control of the herbs. The anti-myocardial ischemia effect of SP is that resveratrol improves cardiac function and inhibits cardiomyocyte apoptosis to protect cardiomyocytes. The present study provides ample evidence for the clinical use of SP, suggesting that this drug has great potential in the treatment of ischemic heart disease.

Lanthanum hydroxide inhibits vascular calcification by regulating the HIF-1 pathway.

The main reason for the high incidence of cardiovascular disease in chronic kidney disease (CKD) patients with vascular calcification (VC) is also the main cause of death in CKD patients. Lanthanum hydroxide (LH) has an inhibitory effect on VC in chronic renal failure; however, the mechanism of its inhibition is poorly defined. Here, we used network pharmacology analysis and found that hypoxia-inducible factor (HIF) is related to VC. In a CKD rat model induced by adenine combined with high phosphorus (1.2%), LH improved the survival rate and inhibited the occurrence and development of VC. In an in vitro study, we found that lanthanum chloride inhibited the occurrence of VC induced by high phosphorus and reduced the production of reactive oxygen species. This study thus revealed that LH can inhibit the occurrence and development of VC by inhibiting the activation of HIF-1.

Protective mechanisms of three antioxidants against T-2 toxin-induced muscle protein deterioration in shrimp.

BACKGROUND: Quercetin (Q), tea polyphenols (TP), and rutin (R) are widely used plant-derived active ingredients. They possess antioxidant, anti-inflammatory, and anti-tumor properties, and can reduce the muscle damage caused by mycotoxins. However, few studies have examined the protective mechanisms of quercetin, tea polyphenols, and rutin on muscle quality. To elucidate their protective mechanisms, shrimp were exposed to both T-2 toxin and these three antioxidants for 20 days in a dose-escalating trial. The changes in the protein composition of shrimp muscle were measured. The target proteins associated with T-2 and antioxidants were screened and identified by non-labeled quantitative proteomics. RESULTS: The T-2 toxin induced abnormal expression of 21 target proteins, leading to the deterioration of muscle proteins in shrimp. The three antioxidants ameliorated the T-2 toxin-induced damage to muscle proteins by increasing the sarcoplasmic and myofibrillar protein content and decreasing the alkali-soluble protein content. Quercetin had the strongest protective effect. The protective processes of these antioxidants involved the upregulation of target proteins involved in carbohydrate metabolism (enolase, malate dehydrogenase), protein translation (elongation factor 1-alpha and eukaryotic translation initiation factor 2 subunit alpha), and cytoskeleton component (actin 2, fast-type skeletal muscle actin 1). Quercetin regulated the largest number of target proteins, making it the best protective agent against T-2 toxin. CONCLUSION: The T-2 toxin (4.80-24.30 mg/kg feed) induced changes in target proteins and muscle composition of shrimp, leading to a deterioration in muscle proteins. Quercetin (2.00-32.00 g/kg feed) had significant protective effects against this deterioration in muscle protein in shrimp. © 2022 Society of Chemical Industry.

Preliminary Report on Intestinal Flora Disorder, Faecal Short-Chain Fatty Acid Level Decline and Intestinal Mucosal Tissue Weakening Caused by Litchi Extract to Induce Systemic Inflammation in HFA Mice.

Certain foods are known as "heating" foods in Chinese medicine. Over-consumption of these foods can lead to symptoms known as "heating up". These symptoms have been shown to be symptoms of systemic low-grade inflammation. However, the mechanism by which these foods cause inflammation is not clear. In this preliminary study, we investigated dysbacteriosis of the gut microbiota as a possible cause of inflammation by litchi, a typical "heating" food. A human flora-associated (HFA) mouse model (donor: n = 1) was constructed. After gavaging the mice with litchi extract suspension at low, medium and high doses (400, 800, 1600 mg/kg·d-1, respectively) (n = 3) for 7 days, the serum levels of inflammatory cytokines, gut microbiota, the concentration of SCFAs and the integrity of the intestinal mucosal barrier were measured. The results revealed significant increases in the abundance of Prevotella and Bacteroides. A significant increase in the abundance of Bilophila and a decrease in Megasomonas was observed in the high-dose group. High-dose litchi intervention led to a decrease of most SCFA levels in the intestine. It also caused a more than two-fold increase in the serum TNF-α level and LPS level but a decrease in the IL-1ß and IL-6 levels. Medium- and high-dose litchi intervention caused widening of the intestinal epithelial cell junction complex and general weakening of the intestinal mucosal barrier as well as reduced energy conversion efficiency of the gut microbiota. These data suggest that litchi, when consumed excessively, can lead to a low degree of systematic inflammation and this is linked to its ability to cause dysbacteriosis of the gut microbiota, decrease SCFAs and weaken the intestinal mucosal tissues.

Contextual prediction modulates musical tension: Evidence from behavioral and neural responses.

Tension is a bridge between music structure and emotion. It is known that tension is affected by prediction in music listening as music unfolds. Combining behavioral and neural responses, the current research investigated how musical predictions influence tension in the process of prediction build-up based on musical context (anticipatory stage) and its integration with upcoming stimuli (integration stage). The results showed that, at the anticipatory stage, compared with high-prediction conditions, in low-prediction conditions tension curve changed faster and unstable, and a larger N5 in ERP response was elicited. Furthermore, at the integration stage, compared with congruent conditions, in incongruent conditions the behavioral rating of tension were higher regardless of the predictability of the final chord; a right negativity and P600 were elicited, and the amplitude of P600 was modulated by the predictability of the final chord. These results indicated that the effect of prediction on tension was modulated by contextual predictability. The findings provide a more comprehensive view on how musical prediction affects musical tension.

Protective role of l-threonine against cadmium toxicity in Saccharomyces cerevisiae.

Environment and food contamination with cadmium (Cd) can cause serious toxicity, posing a severe threat to agricultural production and human health. However, how amino acids contribute to defenses against oxidative stress caused by Cd in cells is not fully understood. As a model eukaryote with a relatively clear genetic background, Saccharomyces cerevisiae has been commonly used in Cd toxicity research. To gain insight into Cd toxicity and cell defenses against it, 20 amino acids were screened for protective roles against Cd stress in S. cerevisiae. The results showed that threonine (Thr, T) had the strongest protective effect against Cd-induced mortality and membrane damage in the cells. Compared to the antioxidant vitamin C (VC), Thr exhibited a higher efficacy in restoring the superoxide dismutase (SOD) activity that was inhibited by Cd but not by H2 O2 in vivo. Thr exhibited evident DPPH (2,2-diphenyl-1-picrylhydrazyl) activity but weak ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-9 sulfonic acid)) scavenging activity, giving it a weaker effect against Cd-induced lipid peroxidation and superoxide radical O2- , compared to VC. More importantly, compared to the chelating agent EDTA, Thr showed stronger chelation of Cd, giving it a stronger protective effect on SOD against Cd than VC in vitro. The results of the in vivo and in vitro experiments revealed that the role Thr plays in cell defenses against Cd may be attributed to its protection of the SOD enzyme, predominantly through the preferential chelation of Cd. Our results provide insights into the protective mechanisms of amino acid Thr that ameliorate Cd toxicity and suggest that a supplement of Thr might help to reduce Cd-induced oxidative damage.

The galloyl moiety enhances the inhibitory activity of catechins and theaflavins against α-glucosidase by increasing the polyphenol-enzyme binding interactions.

The inhibition properties of 10 tea polyphenols against α-glucosidase were studied through inhibition assay, inhibition kinetics, fluorescence quenching and molecular docking. It was found that the inhibitory activity of polyphenols with a 3 and/or 3' galloyl moiety (GM) was much higher than that without a GM. The GM could enter into the active site of α-glucosidase and bind with the catalytic amino acid residues through hydrogen bonding and π-conjugation, thus playing an important role in the competitive inhibition of catechins and theaflavins. The positive linear correlations among the constants characterizing the inhibitory activity and binding affinity of tea polyphenols to α-glucosidase indicate that enzyme inhibition by polyphenols is caused by the binding interactions between them, and that the combination of the characterization methods for polyphenol-glucosidase binding is reasonable. In addition, the in vivo hypoglycemic effects of galloylated polyphenols suggest that the GM may be considered as a pharmaceutical fragment for the alleviation of type II diabetes symptoms through α-glucosidase inhibition.

[Serum of SD rats lavaged by modified Zuojin decoction promotes apoptosis and inhibits proliferation of human gastric cancer cells by activating mitochondrialpathways].

Objective To observe the effect of serum of SD rats lavaged by modified Zuojin decoction on the apoptosis and proliferation of human gastric cancer cells and its mechanism. Methods SD rats were gavaged with modified Zuojin decoction to prepare their sera. Human SGC-7901 and MKN-45 cells were cultured and treated with the sera (0, 25, 50, 100, 200, 400) mL/L. MTT assay was used to observe the effect of drug-containing serum on the proliferation of human gastric cancer cells. Immunofluorescence method was used to detect the expression of ki67 after treatment with the drug-containing serum. The effect of drug-containing serum on the apoptosis of gastric cancer cells was detected by flow cytometry. Western blot analysis was used to detect the protein levels of apoptosis-associated cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, BAX and Bcl2 in SGC-7901 and MKN-45 cells. Results The drug-containing serum significantly inhibited the proliferation and induced the apoptosis of SGC-7901 and MKN-45 cells, and the positive rate of ki67 expression was significantly reduced. The levels of cleaved caspase-3, cleaved caspase-9 and BAX proteins in SGC-7901 and MKN-45 cells increased and the levels of Bcl2 protein decreased. Conclusion The drug-containing serum can significantly inhibit the proliferation and induce the apoptosis of human gastric cancer SGC-7901 and MKN-45 cells, and the mechanism may be related to the activation of mitochondrial pathways.

Compatibility of sodium alginate and konjac glucomannan and their applications in fabricating low-fat mayonnaise-like emulsion gels.

In this study, the compatibility of alginate (Alg) and konjac glucomannan (KGM) in aqueous solutions was evaluated by dilute solution viscometry (DSV). It was found that when Alg: KGM ratio was lower than 6:4 (w/w), Alg and KGM were compatible, which was subsequently confirmed by SEM, AFM and TEM. Moreover, by dispersing emulsified oil droplets into Alg gel matrix, followed by addition of KGM to thicken the system, where the ratio of Alg: KGM was 5:5, a class of emulsion gels with significant thixotropy and viscoelasticity could be obtained. The prepared emulsion gels displayed good thermal stability and freeze-thaw stability, with no oil droplet coalescence observed after heating at 100°C for 30 min or freezing the gels at -18°C for 24 h. Overall, the mixed Alg/KGM system is expected to provide a template for designing low-fat mayonnaise-like food emulsions.

Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation.

BACKGROUND/AIMS: It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS). METHODS: A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed. The biological parameters of serum and urine and the pathological manifestations of kidney tissue were examined. The expression of mRNA and protein of P2X7R and NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and downstream effectors (IL-1ß and IL-18), as well as podocyte-associated molecules, was determined by real-time quantitative PCR and Western blot assay, respectively. RESULTS: The DN rats showed to have developed insulin resistance, elevated fasting blood glucose, increased urinary protein excretion, and serum creatinine level as well as corresponding glomerular pathological alterations including podocyte damages. ACOS significantly antagonized the above changes. The experiments in vivo and in vitro both displayed that the mRNA and protein expression of P2X7R, NLRP3, ASC, caspase1 (procaspase-1 mRNA in the gene level and active caspase-1 subunit P10 in the protein level), IL-1ß, and IL-18 was significantly upregulated and the mRNA and protein expression of podocyte-associated molecules was significantly changed (downregulation of nephrin, podocin, and WT-1 expression and upregulation of desmin expression) indicating podocyte injury in the kidney tissue of DN rats and in the HG-stressed mouse podocytes, respectively. ACOS also significantly antagonized all the above changes. CONCLUSION: Our research work suggests that P2X7R and NLRP3 inflammasome are involved in the pathogenesis of DN, and ACOS can effectively inhibit the high expression of P2X7R and the activation of NLRP3 inflammasome, which may contribute to the therapeutic effects of Ophiocordyceps sinensis.

Pulsed electromagnetic fields alleviate streptozotocin­induced diabetic muscle atrophy.

Diabetic muscle atrophy causes a reduction of skeletal muscle size and strength, which affects normal daily activities. However, pulsed electromagnetic fields (PEMFs) can retard the atrophy of type II fibers (ActRIIB) in denervated muscles. Therefore, the purpose of the present study was to determine whether PEMFs can alleviate streptozotocin (STZ)­induced diabetic muscle atrophy. To do this, 40 Sprague­Dawley (SD) rats were randomly divided into four groups (n=10 per group): The normal control group (NC; nondiabetic rats without treatment); the diabetic mellitus group (DM; STZ­induced rats without treatment); the diabetic insulin­treated group (DT; diabetic rats on insulin treatment, 6­8 U/d twice a day for 6 weeks) as a positive control; and the diabetic PEMFs therapy group (DP; diabetic rats with PEMFs exposure treatment, 15 Hz, 1.46 mT, 30 min/day for 6 weeks). Body weight, muscle strength, muscle mass and serum insulin level were significantly increased in the DP group compared with the DM group. PEMFs also decreased the blood glucose level and altered the activity of metabolic enzymes. PEMFs significantly increased the cross­sectional area of muscle fiber. In addition, PEMFs significantly activated protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and inhibited the activity of myostatin (MSTN), ActRIIB and forkhead box protein O1 (FoxO1) compared with the DM group. Thus indicating that the Akt/mTOR and Akt/FoxO1 signaling pathways may be involved in the promotion of STZ­induced diabetic muscle atrophy by PEMFs. The results of the present study suggested that PEMFs stimulation may alleviate diabetic muscle atrophy in the STZ model, and that this is associated with alterations in multiple signaling pathways in which MSTN may be an integral factor. MSTN­associated signaling pathways may provide therapeutic targets to attenuate severe diabetic muscle wasting.

Tea polyphenols enhance binding of porcine pancreatic α-amylase with starch granules but reduce catalytic activity.

The effects of tea polyphenols on binding of porcine pancreatic α-amylase (PPA) with normal maize starch granules were studied through solution depletion assays, fluorescence spectroscopy and initial rate kinetics. Only polyphenols which have inhibitory activity against PPA increased the binding of PPA with starch. The results are consistent with a binding equilibrium between polyphenols, starch and PPA. The dissociation constant (Kd) for PPA binding was decreased by tea polyphenols, with the effects greater for theaflavins than catechins and for galloylated than non-galloylated polyphenols. Tea polyphenols were also shown to increase the binding rate of PPA to starch. In addition, there were positive linear correlations between 1/Kd and reciprocal of competitive inhibition constant (1/Kic) and between 1/Kd and fluorescence quenching constant (KFQ). Despite the greater amount of PPA on the granules, starch hydrolysis is reduced because the polyphenol inhibition of PPA persists after binding to starch.

Comparison and multivariate statistical analysis of anthocyanin composition in Lycium ruthenicum Murray from different regions to trace geographical origins: The case of China.

Anthocyanin composition in forty-five Lycium ruthenicum Murray (LRM) samples grown in China was identified by high-performance liquid chromatography-electrospray ionisation-mass spectrometry (HPLC-ESI-MS) and quantified by HPLC with a diode array detector (HPLC-DAD). The results showed that the overall pattern of anthocyanin composition of LRM from different provinces was the same, while the individual and total anthocyanin concentrations, were significantly different, indicating an important impact of geographical origin on anthocyanin composition, which can be considered as credible indices for LRM classification. Principal component analysis (PCA) and linear discriminant analysis (LDA) were applied to develop discrimination models for the anthocyanin concentrations. PCA clearly separated the LRM based on its geographical origins. LDA satisfactorily categorized the samples by providing a 100% success rate based on geographical origins. The results obtained could be used to trace the geographical origin of LRM.

Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma.

BACKGROUND: Kinase inhibitor sorafenib is the most widely used drug for advanced HCC clinical treatment nowadays. However, sorafenib administration is only effective for a small portion of HCC patients, and the majority develop sorafenib-resistance during treatment. Thus, it is urgent to discover the endogenous mechanism and identify new pharmaceutical targets of sorafenib-resistance. METHODS: Pregnane X receptor (PXR) was detected by immunohistochemistry and quantitative PCR. GST-pull down and LC-MS/MS was used to detect the interaction of PXR and Sorafenib. To test the properties of HCC tumor growth and metastasis, in vivo tumor explant model, FACS, trans-well assay, cell-survival inhibitory assay and Western blot were performed. In terms of mechanistic study, additional assays such as ChIP and luciferase reporter gene assay were applied. RESULTS: In the present work, we found high PXR level in clinical specimens is related to the poor prognosis of Sorafenib treated patients. By the mechanistic studies, we show that sorafenib binds to PXR and activates PXR pathway, and by which HCC cells develop sorafenib-resistance via activating. Moreover, PXR overexpression helps HCC cells to persist to sorafenib treatment. CONCLUSION: This study reports the endogenous sorafenib-resistance mechanism in HCC cells, which offers an opportunity to design new therapeutic approaches for HCC treatment. GENERAL SIGNIFICANCE: PXR mediates sorafenib-resistance in HCC cells and targeting PXR can be a useful approach to facilitate HCC treatment.