Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

[Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells].

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Recovery trajectories of the bacterial community at distances in the receiving river under wastewater treatment plant discharge.

Microbes in rivers are an important part of the biogeochemical cycle in aquatic ecosystems, and understanding the major factors that influence the composition of microbial communities has an important role in assessing and improving ecosystem functioning. A high-throughput 16 S rRNA gene sequencing technique was employed to sequence bacterial communities in 21 sediment samples and 21 water samples from an urban river WWTP (wastewater treatment plant) discharge. A systematic study of changes in bacterial community composition in downstream river sediment and water was conducted. The study found that compared with the bacterial diversity in the natural upstream area of the wastewater outfall, the bacterial diversity in the sediment lower reaches decreased significantly, while the bacterial abundance and diversity in the water increased significantly. The Mantel test and redundancy analysis showed that the downstream distance and physicochemical properties were significantly related to the succession of bacterial communities in the sediment downstream of the WWTP discharge. Among them, TOC (total organic carbon) was the most important factor affecting the change in the bacterial community in the downstream sediment. The physicochemical properties were significantly correlated with the succession of bacterial communities in the water downstream of the WWTP discharge. Among them, TN (total nitrogen), PO43--P (phosphorus phosphate) and TP (total phosphorus) were the main factors that affected the change in the bacterial community in the downstream water. Key taxa in the co-occurrence network at different distances downstream reflected the depth of the effect of the WWTP effluent on the bacterial community. The bacterial community in the lower reaches of the river sediment showed a strong recovery ability under the influence of pollutants, while the bacterial community in the lower reaches of the river water was difficult to recover under the influence of pollutants. In general, pollutants contained in effluent are the key to changing the composition of bacterial communities in the lower reaches of the river, but exogenous bacteria in effluent are not. This study provides a basis for further improving the effluent discharge standards of WWTPs in the future.

The Chemical Signatures of Water Extract of Zingiber officinale Rosc.

Background: Ginger (Z. officinale Rosc.) is a common herb and is widely used as a diet-based or home therapy in traditional medicine worldwide. However, fresh ginger turns into dried ginger after kiln drying and shows a different treatment effect in clinical practice. Objective: To characterize the changes of major bioactive constituents in dried ginger after the processing of fresh ginger. Methods: A novel, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC−QTOF/MS) method was established to characterize the changes in the bioactive constituents of dried ginger. The novel strategy was split into two steps: firstly, the MS selected the most intense precursor ions of tandem MS; then, target MS/MS acquisition with different collision energies (10, 20, and 40 eV) was used to characterize the compound's accurate MS/MS spectra and compare the MS/MS spectrum with the building MS reference library and reference standards. Result: Fifty-three compounds, including diarylheptanoids, gingerols, gingerodiols, gingerdiones, and shogaol-related compounds, were identified based on summarized fragmentation patterns. Fifteen out of fifty-three compounds were diarylheptanoids, which was different from fresh ginger. Conclusion: These identified compounds could be used to characterize the quality of dried ginger, pharmacologic studies should focus on diarylheptanoids explaining the different treatment effects between fresh ginger and dried ginger.

Robust therapeutic effects on COVID-19 of novel small molecules: Alleviation of SARS-CoV-2 S protein induction of ACE2/TMPRSS2, NOX2/ROS, and MCP-1.

While new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge to prolong the pandemic of COVID-19, robust and safe therapeutics are in urgent need. During the previous and ongoing fight against the pandemic in China, Traditional Chinese Medicine (TCM) has proven to be markedly effective in treating COVID-19. Among active ingredients of TCM recipes, small molecules such as quercetin, glabridin, gallic acid, and chrysoeriol have been predicted to target viral receptor angiotensin-converting enzyme 2 (ACE2) via system pharmacology/molecular docking/visualization analyses. Of note, endothelial dysfunction induced by oxidative stress and inflammation represents a critical mediator of acute respiratory distress syndrome (ARDS) and multi-organ injuries in patients with COVID-19. Hence, in the present study, we examined whether quercetin, glabridin, gallic acide and chrysoeriol regulate viral receptors of ACE2 and transmembrane serine protease 2 (TMPRSS2), redox modulator NADPH oxidase isoform 2 (NOX2), and inflammatory protein of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to mediate therapeutic protection against COVID-19. Indeed, quercetin, glabridin, gallic acide and chrysoeriol completely attenuated SARS-CoV-2 spike protein (S protein)-induced upregulation in ACE2 protein expression in endothelial cells. In addition, these small molecules abolished S protein upregulation of cleaved/active form of TMPRSS2, while native TMPRSS2 was not significantly regulated. Moreover, these small molecules completely abrogated S protein-induced upregulation in NOX2 protein expression, which resulted in alleviated superoxide production, confirming their preventive efficacies against S protein-induced oxidative stress in endothelial cells. In addition, treatment with these small molecules abolished S protein induction of MCP-1 expression. Collectively, our findings for the first time demonstrate that these novel small molecules may be used as novel and robust therapeutic options for the treatment of patients with COVID-19, via effective attenuation of S protein induction of endothelial oxidative stress and inflammation.

Direct autotransfusion in the management of acute pericardial tamponade during catheter ablation for atrial fibrillation: An imperfect but practical method.

Background: Acute pericardial tamponade (APT) is one of the most serious complications of catheter ablation for atrial fibrillation (AF-CA). Direct autotransfusion (DAT) is a method of reinjecting pericardial blood directly into patients through vein access without a cell-salvage system. Data regarding DAT for APT are rare and provide limited information. Our present study aims to further investigate the safety and feasibility of DAT in the management of APT during the AF-CA procedure. Methods and results: We retrospectively reviewed 73 cases of APT in the perioperative period of AF-CA from January 2014 to October 2021 at our institution, among whom 46 were treated with DAT. All included patients successfully received emergency pericardiocentesis through subxiphoid access guided by X-ray. Larger volumes of aspirated pericardial blood (658.4 ± 545.2 vs. 521.2 ± 464.9 ml), higher rates of bridging anticoagulation (67.4 vs. 37.0%), and surgical repair (6 vs. 0) were observed in patients with DAT than without. Moreover, patients with DAT were less likely to complete AF-CA procedures (32/46 vs. 25/27) and had a lower incidence of APT first presented in the ward (delayed presentation) (8/46 vs. 9/27). There was no difference in major adverse events (death/disseminated intravascular coagulation/multiple organ dysfunction syndrome and clinical thrombosis) (0/0/1/0 vs. 1/0/0/0), other potential DAT-related complications (fever/infection and deep venous thrombosis) (8/5/2 vs. 5/3/1), and length of hospital stay (11.4 ± 11.6 vs. 8.3 ± 4.7 d) between two groups. Conclusion: DAT could be a feasible and safe method to deal with APT during AF-CA procedure.

Evaluation of the Effect of Integrated Care on Preoperative Anxiety in Day Surgery Patients Based on the MVPA Framework.

Objective: To investigate the effect of receiving comprehensive care on preoperative anxiety in patients admitted to the operating room at different times. Methods: A generative model was applied to a patient's preoperative anxiety aid diagnostic model and used to address preoperative anxiety due to the patient. Group ICA first constructed a whole-brain dynamic functional connectivity network, and an initial dataset was constructed by Kendall's ranking correlation coefficient method; then, an expanded dataset was constructed by a conditional deep convolutional generative adversarial network (CDCGAN), and finally, a dynamic classification study of patients with preoperative anxiety and healthy subjects was conducted by feature selection and discriminant models in turn. Seventy patients who entered the operating theatre at different times were retrospectively analyzed. Children who entered the operating theatre after 14:00 were included in the control group (n = 35), and those who entered between 12:00 were included in the observation group (n = 35). Patients in both groups were given comprehensive care, and preoperative anxiety was compared between the two groups. Results: The earlier the patients entered the operating room, the lower the preoperative anxiety. Conclusion: Comprehensive care could reduce the patients' preoperative anxiety, keep their emotions stable, and improve their compliance with treatment.

Ginsenoside Rg1 promoted the wound healing in diabetic foot ulcers via miR-489-3p/Sirt1 axis.

PURPOSE: Diabetic foot ulcers (DFUs) are common complications of high severity for diabetes. Ginsenoside Rg1 (Rg1) has the potential for diabetes and cardiovascular diseases therapy. This research aimed at exploring the regulation of Rg1 on DFUs treatment and the underlying mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) incubated with high-glucose culture medium were established for induction of diabetes model. The MTT assay, Annexin V/PI assay and oxidative stress detection were carried out on high-glucose-induced HUVECs. Dual-luciferase reporter assay was performed to prove the interaction of miR-489-3p and Sirt1. DFUs model was established to determine the efficiency of Rg1 and miR-489-3p in wound closure of DFUs in vivo. RESULTS: Rg1 promoted cell proliferation, migration and angiogenesis, and reduced cell apoptosis in high-glucose-induced HUVECs. Knockdown of miR-489-3p alleviated the high-glucose-induced damage to HUVECs, while overexpression of miR-489-3p attenuated the protection effects of Rg1. Overexpression Sirt1 promoted wound healing in DFUs and Sirt1 was a direct target of miR-489-3p. In addition, animal experiments demonstrated that Rg1 promoted wound closure by regulating miR-489-3p/Sirt1 axis. CONCLUSIONS: Rg1 alleviated the DFUs by increasing Sirt1 expression via miR-489-3p downregulation and promoting activation of PI3K/AKT/eNOS signaling.

[Effect of transcutaneous electric acupoints stimulation on vascular endothelial function and inflammatory factors after percutaneous coronary intervention].

OBJECTIVE: To observe the effect of transcutaneous electric acupoints stimulation (TEAS) on vascular endothelial function and inflammatory factors after percutaneous coronary intervention (PCI) in patients. METHODS: A total of 94 patients with coronary heart disease and undergoing PCI were randomized into a TEAS group and a sham-TEAS group, 47 cases in each one. In the TEAS group, TEAS started at unilateral Neiguan (PC6) and Ximen (PC4) 30 min before PCI till the end of PCI. In the sham-TEAS group, the procedure and persistent time were same as the TEAS group, but no electric stimulation was performed. Before treatment and at 8 h and 24 h after PCI, the levels of serum endothelin-1 (ET-1), von Willebrand factor (vWF), nitric oxide (NO), blood flow dependent diastolic function (FMD), interleukin-6 (IL-6), inteleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9) and high-sensitivity C-reactive protein (hs-CRP) were detected in the patients successively. RESULTS: Compared with the levels before PCI, the levels of ET-1 and vWF were all increased at 8 h and 24 h after PCI in the two groups (P<0.05) and the levels in the TEAS group were remarkably lower than those in the sham-TEAS group (P<0.05). Compared with the levels before PCI, the levels of NO and FMD at 8 h and 24 h after PCI were all reduced in the two groups (P<0.05) and the levels in the TEAS group were higher obviously than those in the sham-TEAS group (P<0.05). Compared with the levels before PCI, the levels of hs-CRP, MMP-9, IL-6 and IL-10 were all increased at 8 h and 24 h after PCI in the two groups (P<0.05); Compared with the sham-TEAS group, the levels of hs-CRP, MMP-9 and IL-6 were reduced and the level of IL-10 was increased at 8 h and 24 h after PCI in the TEAS group (P<0.05). CONCLUSION: TEAS effectively improves the vascular endothelial function and reduces serum inflammatory factors after PCI.

Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: Efficacies and mechanisms.

COVID-19 has remained an uncontained, worldwide pandemic. While battling for the disease in China, six Traditional Chinese Medicine (TCM) recipes have been shown to be remarkably effective for treating patients with COVID-19. The present review discusses principles of TCM in curing infectious disease, and clinical evidence and mechanisms of the 6 most effective TCM recipes used in treating COVID-19 in 92% of all of the confirmed cases in China. Applications of TCM and specific recipes in the treatment of other viral infections, such as those caused by SARS-CoV, MERS-CoV, hepatitis B virus, hepatitis C virus, influenza A virus (including H1N1 and H7N9), influenza B, dengue virus as well as Ebola virus, are also discussed. Among the 6 TCM recipes, Jinhua Qinggan (JHQG) granules and Lianhua Qingwen (LHQW) capsules are recommended during medical observation; Lung Cleansing and Detoxifying Decoction (LCDD) is recommended for the treatment of both severe and non-severe patients; Xuanfeibaidu (XFBD) granules are recommended for treating moderate cases; while Huashibaidu (HSBD) and Xuebijing (XBJ) have been used in managing severe cases effectively. The common components and the active ingredients of the six TCM recipes have been summarized to reveal most promising drug candidates. The potential molecular mechanisms of the active ingredients in the six TCM recipes that target ACE2, 3CLpro and IL-6, revealed by molecular biological studies and/or network pharmacology prediction/molecular docking analysis/visualization analysis, are fully discussed. Therefore, further investigation of these TCM recipes may be of high translational value in enabling novel targeted therapies for COVID-19, potentially via purification and characterization of the active ingredients in the effective TCM recipes.

Sedum sarmentosum Total Flavonoids Alleviate Schistosomiasis-Induced Liver Fibrosis by Altering TGF-ß1 and Smad7 Expression.

OBJECTIVES: Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. Sedum sarmentosum total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism. METHODS: Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also measured the expression of transforming growth factor-beta 1 (TGF-ß1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry. RESULTS: Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis (P < 0.05). Each dose of SSTF also significantly reduced TGF-ß1 protein expression and mRNA levels in the liver tissues (P < 0.05). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels (P < 0.05). Immunohistochemistry showed that each dose of SSTF reduced TGF-ß1 protein expression (P < 0.05). CONCLUSION: Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-ß1/Smad7 pathway.

Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium.

BACKGROUND: BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model. METHODS: In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues. RESULTS: BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group. CONCLUSION: These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.

Right free-wall accessory pathway with branched atrial insertions: Clinical, electrocardiographic, and electrophysiological characteristics.

BACKGROUND: Right free-wall (RFW) accessory pathway (AP) with branched atrial insertions is a rare, underrecognized AP that may be associated with initial ablation failure. OBJECTIVE: The purpose of this study was to investigate the clinical and electrophysiological characteristics of this AP. METHODS: From January 2011 to March 2018, 10 patients identified with branched RFW-AP were enrolled in this study, and 30 consecutive patients with conventional RFW-APs served as control group. Right atrium (RA) was activation-mapped and 3-dimensionally reconstructed during AP-mediated orthodromic tachycardia or right ventricular pacing. Atrial insertions were defined as the earliest breakout sites, and their relationship with the tricuspid annulus (TA) were described and analyzed. RESULTS: An average of 3 separate atrial insertions on the atrial side were documented among these 10 cases (5 female and 5 male; mean age 38.0 ± 13.9 years). All atrial insertions were away from the TA. The nearest atrial insertions averaged 15.9 ± 3.4 mm away from the TA, and the farthest atrial insertions were 22.6 ± 5.7 mm away from the TA. Anterograde and retrograde AP conduction remained unaffected after ablation of the first earliest breakout site but were eliminated by ablating all insertions after an average of 2.5 (range 2-2.5) remaps, 3 sites of ablation (range 2.5-4.5), 21 (range 15.5-37.8) radiofrequency applications, and 659.5 (range 464.3-1144.3) seconds of radiofrequency ablation duration. After 12-month follow-up, no patients reported AP conduction recovery or recurrent tachycardia. CONCLUSION: RFW-AP with branched atrial insertions is an atypical AP variant and featured by >1 distinct atrial insertions on atrial side. Stepwise ablation rather than single focal ablation is required to eliminate all retrograde conduction.

Effects of licorice extracts on the pharmacokinetics of brucine in rats and its possible mechanism.

The detoxification effects of licorice are believed to be related to its pharmacokinetic (PK) interference. This paper aimed to evaluate the effects of licorice water extracts (LWE) on the pharmacokinetics of brucine. Rats were administered brucine and/or LWE. The pharmacokinetic behavior of brucine and bioactive components of licorice were quantified by HPLC-MS/MS. P-glycoprotein (P-gp) inhibitor verapamil, real time PCR, vesicular transport assay and everted gut sacs were employed to investigate its possible mechanism. We found LWE reduced the Cmax and AUC of oral brucine in a dose-dependent way. In contrast, the AUC values of intraperitoneal brucine showed no significant difference between LWE treated and untreated rats, which indicating the intestinal absorption of brucine was influenced by LWE. We found that high dose of LWE activated the transport activity of P-gp in vesicular transport assay, while the mRNA level of P-gp in the intestinal was not affected by licorice. Moreover, high dose of LWE decreased the intestinal absorption of brucine in the everted gut sacs model, which could over turned by verapamil. These results suggested that a single high dose of LWE could impair the intestine absorption of brucine, and its potential mechanism may be mediated by P-gp in intestine.

Licorice Extracts Attenuate Nephrotoxicity Induced by Brucine Through Suppression of Mitochondria Apoptotic Pathway and STAT3 Activation.

Licorice, one of the most widely used medicinal herbs in East Asia, has effects such as anti-inflammation, antioxidant, and detoxifying. This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity. Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice. The content of blood urea nitrogen and creatinine in serum, the activities of superoxide dismutase and content of glutathione, malonaldehyde in kidney tissue were detected. Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney. The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis. The results illustrated that treatment with licorice extracts (LE) significantly protected against the brucine-induced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine, attenuating pathologic damage. The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione, promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde. In addition, LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3 (STAT3) activation. Taken together, these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway. More importantly, the renoprotective effects may be mediated, at least partly, by preventing the activation of STAT3 protein.

Electroacupuncture decreases Netrin-1-induced myelinated afferent fiber sprouting and neuropathic pain through µ-opioid receptors.

Purpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of µ-opioid receptors. Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a µ-opioid receptor antagonist, beta-funaltrexamine (ß-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB). Results: Treatment with 2 Hz EA at "Huantiao" (GB30) and "Yanglingquan" (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the µ-opioid receptor antagonist ß-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells. Conclusions: Through activation of µ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.

Triterpenoids, megastigmanes and hydroxycinnamic acid derivatives from Anisomeles indica.

Six triterpenoids (1-6), four megastigmanes (7-10) and five hydroxycinnamic acid derivatives (11-15) were isolated from the aerial part of Anisomeles indica (Lamiaceae). Of these components, compound 1 was identified to be a new triterpenoid with the structure of 2α,3α,19α-trihydroxyurs-12,20(30)-dien-28-oic acid based on extensive analysis of MS, 1D and 2D NMR spectroscopic data, while compounds 2-13 were obtained for the first time from Anisomeles species.

Electroacupuncture potentiates peripheral CB2 receptor-inhibited chronic pain in a mouse model of knee osteoarthritis.

PURPOSE: Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, with chronic pain as its typical symptom. Although studies have shown that an activated peripheral CB2 receptor can reduce acute pain, whether the CB2 receptor is involved in electroacupuncture (EA) inhibiting chronic pain and the involved mechanism remains unclear. The aim of this study was to investigate whether EA may strengthen peripheral CB2 receptor-inhibited chronic pain in a mouse model of KOA. MATERIALS AND METHODS: KOA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the left knee joint of mice. Thermal hyperalgesia was tested with the hot plate test, and mechanical allodynia was quantified using von Frey filaments. The expression of CB2 receptor and IL-1ß were quantified by using immunofluorescence labeling. RESULTS: EA treatment at 2 Hz+1 mA significantly increased the expression of CB2 receptor in fibroblasts and decreased the expression of IL-1ß in the menisci compared with that in the KOA group. However, EA had no effect on the expression of IL-1ß in CB2-/- mice. At 2 Hz+1 mA, EA significantly increased mechanical threshold, thermal latency, and weight borne after KOA modeling. However, knockout of the CB2 receptor blocked these effects of EA. After 2 Hz+1 mA treatment, EA significantly reduced the Osteoarthritis Research Society International (OARSI) score after KOA modeling. However, EA had no significant effect on the OARSI score in CB2-/- mice. CONCLUSION: EA reduced the expression of IL-1ß by activating the CB2 receptor, thus inhibiting the chronic pain in the mouse model of KOA.

[Relationship between vegetation C, N, P stoichiometry and species diversity in sand land.] / æ²™åœ°æ¤è¢«ç¢³æ°®ç£·åŒ–å­¦è®¡é‡ç‰¹å¾ä¸Žç‰©ç§å¤šæ ·æ€§çš„å ³ç³».

Vegetation stoichiometry represents plant nutrition limitation status. Whether it can affect the species diversity of plant community remains to be explored. In this study, we examined plant carbon (C), nitrogen (N), phosphorus (P) concentrations and stoichiometry, and further analyzed the relationship between stoichiometry and species diversity in Artemisia ordosica community and Salix psammophila community in sand land of the Ningxia Habahu National Nature Reserve. The results showed that, for the S. psammophila community growing in mobile and semi-fixed sand dunes, there was a significant negative correlation between Simpson index and vegetation C/N ratio, but no significant correlation between Simpson index and vegetation N/P ratio. For A. ordosica community distributed in semi-fixed and fixed dunes, the Shannon index had a significant positive correlation with vegetation N/P ratio and a significant negative correlation with vegetation C/N ratio. Combined the vegetation stoichiometry with the results of regression analysis (RDA), P concentration and thus N/P ratio had different influences on the species diversity for A. ordosica community and S. psammophila community. Our results showed that vegetation stoichiometry has an important influence on species diversity of plant community in sand land.