[Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine].

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

Efficacy of Forsythia suspensa (Thunb.) Vahl on mouse and rat models of inflammation-related diseases: a meta-analysis.

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation. Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2. Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase. Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.

Awake Unilateral Biportal Endoscopic Decompression Under Local Anesthesia for Degenerative Lumbar Spinal Stenosis in the Elderly: A Feasibility Study with Technique Note.

Purpose: Here, we introduce a novel strategy of awake unilateral biportal endoscopic (UBE) decompression, which applies conscious sedation combined with stepwise local anesthesia (LA) as an alternative to general anesthesia (GA). The study aims to evaluate the feasibility of awake UBE decompression for degenerative lumbar spinal stenosis (DLSS) in elderly patients. Patients and Methods: This retrospective study included 31 consecutive patients who received awake UBE decompression for DLSS in our institution from January 2021 to March 2022. Clinical results were evaluated using patient-reported outcomes measures (PROM) including visual analog scale for leg pain (VAS-LP), Oswestry Disability Index (ODI), and modified MacNab criteria. The anesthesia effectiveness and intraoperative experience were evaluated by intraoperative VAS and satisfaction rating system. Results: UBE decompression was successfully performed in all patients under LA combined with conscious sedation. 26 (83.9%) patients rated the intraoperative experience as satisfactory (excellent or good) and 5 (16.1%) as fair. The mean intraoperative VAS was 3.41±1.26. The VAS and ODI at each follow-up stage after surgery were significantly improved compared to preoperative scores (p < 0.01). At the last follow-up, 28 patients (90.3%) classified the surgical outcome as good or excellent, and 3 (9.7%) as fair. There were no serious complications or adverse reactions observed in the study. Conclusion: Our preliminary results suggest that awake UBE decompression is a feasible and promising alternative for elderly patients with DLSS.

Application of in vivo brain imaging technology in the basic research of acupuncture-moxibustion for encephalopathy. / æ´»ä½“è„‘æˆåƒæŠ€æœ¯åœ¨é’ˆç¸è„‘ç— åŸºç¡€ç ”ç©¶ä¸­çš„åº”ç”¨.

Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.

Bavachin induces liver injury and cell apoptosis by targeting Wnt/ß-catenin/DRP1 signaling pathway mediated mitochondrial dysfunction.

Psraleae Fructus (PF) is a well-known traditional Chinese medicine in China. While numerous liver injury reports caused by PF limits its clinical application. Bavachin, a flavonoid compound isolated from the fruits of Psoralea corylifolia L., has been validated to induce direct apoptosis in hepatocytes and liver tissues in our previous studies. However, the subcellular mechanisms of bavachin induced liver injury is still elusive. Here, utilizing 6-week-old C57BL/6 J mice and human embryonic hepatocytes (L02 cells), we report that bavachin activates dynamic-related protein 1 (DRP1) mediated excess mitochondrial fission and endoplasmic reticulum (ER) stress related apoptosis via Wnt/ß-catenin signaling pathway. Notably, DRP1 knockdown or XAV-939 induced Wnt/ß-catenin inhibition decreased bavachin-induced ER stress and cell apoptosis in L02 cells. In addition, bavachin impaired mitochondrial structural and function in the mice liver tissues. Mdivi-1, a mitochondrial fission inhibitor targeting DRP1, prevented bavachin-induced mitochondrial and ER structural damage, ER stress, and liver injury. Our results demonstrated that bavachin induced mitochondrial fission plays a crucial role in bavachin induced ER stress related liver injury, via the mechanism that involved activation of Wnt/ß-catenin signaling pathway.

Role of SIRT5 in the analgesic effectiveness of moxibustion at ST36 in mice with inflammatory pain.

Sirtuine5 (SIRT5) is an important molecule involved in the pathology of inflammatory diseases. To investigate the impact of SIRT5 on the analgesic effectiveness of moxibustion, we established a complete Freund's adjuvant- (CFA-) induced inflammatory pain in mice model. Moxibustion was applied at the Zusanli (ST36) acupoint in mice with inflammatory pain. The analgesic effectiveness was evaluated by thermal hyperalgesia and mechanical allodynia tests in the right paws after CFA injection. The expression of inflammatory cytokines, including the pro-inflammatory factors IL-1ß and TNF-α, and the anti-inflammatory factors IL-4 and TGF-ß expressions, was evaluated using by ELISA. Furthermore, SIRT5 was evaluated by immunofluorescence and western blotting. The results showed that, compared with the CFA group, both thermal and mechanical pain thresholds increased with moxibustion and the SIRT5 inhibitor MC3482 intervention at ST36. Additionally, compared to the CFA-induced group, the inflammatory mediators, including IL-1ß and TNF-α, decreased, while the anti-inflammatory cytokines IL-4 and TGF-ß increased with moxibustion and MC3482 ST36 acupoint injection. Western blot results showed a decreased expression of SIRT5 at the ST36 site with moxibustion and MC3482 injection, compared to the CFA-induced group. SIRT5 expression in the right paw of mice injected with moxibustion and MC3482 was higher than that in the CFA-induced group. This study revealed that SIRT5 expression is involved in moxibustion analgesia and may be a potential mediator in the regulation of analgesia.

Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF / 中山大学学报(医学科学版)

ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor （M-CSF） in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups， (n = 10 mice/group, half male and half female). The albumin control group （BSA， 0.3 μg）， low dose M-CSF group （L M-CSF， 0.075 μg） and high dose M-CSF group （H M-CSF， 0.3 μg） received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration， von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold （PWT） in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin， calcitonin gene-related peptide （CGRP） and phosphorylated ERK1/2 （p-ERK） in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice， only high dose of M-CSF caused mechanical allodynia， whereas in male mice both doses produced marked allodynia. Mechanically， high-dose M-CSF induced massive aggregation of subcutaneous macrophages （marked by Iba1） in male and female mice， but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion （DRGs）. Notably， CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly， the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus disease 2019: A meta-analysis of randomized controlled trials.

BACKGROUND: : Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs). METHODS AND ANALYSIS: : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes. RESULTS: : A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61-3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08-3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29-0.74), shorten the duration of fever (MD = -1.00, 95% CI -1.17 to -0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone. CONCLUSION: : Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.

Clinical observation on wheat grain moxibustion for chronic superficial gastritis of spleen-stomach deficiency and cold / 中国针灸

OBJECTIVE@#To compare the clinical effect of wheat grain moxibustion and warming acupuncture on chronic superficial gastritis of spleen-stomach deficiency and cold.@*METHODS@#A total of 200 patients with chronic superficial gastritis of spleen-stomach deficiency and cold were randomly divided into a wheat grain moxibustion group (100 cases, 13 cases dropped off ) and a warming acupuncture group (100 cases, 16 cases dropped off ). The acupoints of Zhongwan (CV 12), Tianshu (ST 25), Qihai (CV 6), Liangqiu (ST 34) and Zusanli (ST 36) were selected in both groups. The patients in the wheat grain moxibustion group were treated with wheat grain moxibustion, and 5 cone were given on every acupoint each time. Moxibustion was performed after acupuncture in the warming acupuncture group, and 3 cone each acupoint. Both groups were treated every other day for 15 times. The scores of clinical symptoms and signs, scores of physical component summary (PCS) and mental component summary (MCS) of quality of life in the two groups were recorded before and after treatment and during follow-up 1 month after treatment, and the clinical effects of the two groups were evaluated after treatment and during follow-up.@*RESULTS@#After treatment and during follow-up, the scores of clinical symptoms and signs of the two groups were lower than before treatment (@*CONCLUSION@#The wheat grain moxibustion can effectively improve the clinical symptoms, signs and quality of life in patients with chronic superficial gastritis of spleen-stomach deficiency and cold, and its long-term effect is better than warming acupuncture.

Chinese Patent Medicines in the Treatment of Coronavirus Disease 2019 (COVID-19) in China.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus drug treatment. Traditional Chinese Patent Medicines (CPMs) have, however, been widely used to treat COVID-19 in China, and a number of clinical practice results have shown them to have a significant role in its treatment. Consequently, numerous guidelines and expert consensus have recommended the use of CPMs to treat COVID-19. AIM OF THE STUDY: The objectives of this review are to provide up-to-date information on the pharmacology and clinical research on CPMs in the treatment of COVID-19, discuss the research findings, and to better guide clinical application and scientific research on CPMs in the treatment of COVID-19. METHODS: The frequencies of CPM recommendations by guidelines and expert consensus for treatment of COVID-19 in China were ranked. This report identifies the top 10 CPMs, which include Huoxiang Zhengqi capsule (HXZQC), Lianhua Qingwen capsule (LHQWC), Jinhua Qinggan granule (JHQGG), Shufeng Jiedu capsule (SFJDC), Tanreqing injection (TRQI), Xiyanping injection (XYPI), Xuebijing injection (XBJI), Shenfu injection (SFI), Shengmai injection (SMI), and Angong Niuhuang pill (AGNHP). Relevant studies from 2000 to 2020 on these top 10 CPMs, covering usage, dosage, mechanism, curative effect, and precautions, were collected from pharmacopoeia, reports, and theses via library and digital databases (including PubMed, CNKI, Google Scholar, Web of Science, and Elsevier). RESULTS: The properties of the top 10 CPMs included antiviral, antibacterial, anti-inflammatory, antipyretic and analgesic, anti-acute lung injury, anti-shock, immune regulation, and enhancement of pulmonary function. In addition, clinical research results and Chinese treatment data showed that the CPMs had good therapeutic efficacy in the treatment of COVID-19, and adverse reactions were minimal. CONCLUSIONS: Knowledge of the characteristics of the top 10 CPMs and precautions that should be taken may help clinicians to rationally improve therapeutic efficacy, and promote the role of Chinese Medicine in the control of the COVID-19 global epidemic.

Clinical observation of acupuncture plus Frenkel exercises for ataxia after cerebral stroke / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of mind-refreshing and balance-restoring needling method combined with Frenkel exercises in treating ataxia after cerebral stroke. Methods: The recruited 120 patients were randomized into an observation group and a control group, with 60 cases in each group. The control group was intervened by mind-refreshing and balance-restoring needling method, while the observation group was given additional lower-limb Frenkel exercises. Before and after treatment and at the follow-up, the ataxic lower-limb function was scored using Berg balance scale (BBS) and international cooperative ataxia rating scale (ICARS), and Barthel index (BI) was adopted to score the activities of daily living (ADL). Results: After treatment, the markedly effective rate was 70.2％ and the total effective rate was 96.5％ in the observation group, versus 39.7％ and 87.9％ in the control group, and the differences in the markedly effective rate and the total effective rate were statistically significant (P<0.01, P<0.05). The intra-group comparisons showed that the BBS, ICARS and BI scores after treatment and at the follow-up were significantly different from those before treatment in both groups (all P<0.01).There were significant differences in the BBS score between the two groups after treatment and at the follow-up (P<0.05, P<0.01); the between-group differences in the ICARS and BI scores were statistically insignificant after treatment (both P>0.05), while the between-group differences in the ICARS and BI scores were statistically significant at the follow-up (both P<0.05). The interaction effects between the scoring time of BBS and BI and the group factor were statistically significant (P<0.01, P<0.05). Conclusion: Mind-refreshing and balance-restoring needling can effectively improve the lower-limb ataxic symptoms and ADL after stroke; when combined with Fenkel exercises, this needling method can produce more significant efficacy.

Clinical Observations on Wheat-grain Size Cone Moxibustion plus Acupuncture for Mild to Moderate Carpal Tunnel Syndrome / 上海针灸杂志

Objective To investigate the effect of wheat-grain size cone moxibustion plus acupuncture on related high-frequency ultrasonographic indicators before and after its treatment of mild to moderate carpal tunnel syndrome and explore its mechanism of action. Method Sixty patients were randomized to an acupuncture group (20 cases) and a wheat-grain size cone moxibustion groups (40 cases). The acupuncture group received acupuncture at affected-side points Daling (PC7), Hegu (LI4), Neiguan (PC6) and Shousanli (LI10). The wheat-grain size cone moxibustion group received wheat-grain size cone moxibustion on point Daling and acupuncture at the other points. Treatment was given once every other day for a total of 10 times. The thickness of the transverse carpal ligament, the cross-sectional area of the median nerve at the level of the pisiform bone and the flattening ratio at the level of the hamate hook were measured by high frequency ultrasonography before and after treatment. The clinical therapeutic effect was evaluated using the SSS score. Result After treatment, the SSS score decreased in both groups compared with before (P<0.05) and was lower in the wheat-grain size cone moxibustion group than in the acupuncture group (P<0.05). The cure and marked efficacy rate was 71.1％ in the wheat-grain size cone moxibustion groupwhich was higher than 42.1％ in the acupuncture group (P<0.05). There were no statistically significant pre-/post-treatment differences in the thickness of the transverse carpal ligament and the flattening ratio at the level of the hamate hook in the two groups (P>0.05). After treatment, the cross-sectional area of the median nerve at the level of the pisiform bone decreased in both groups compared with before (P<0.05) and was smaller in the wheat-grain size cone moxibustion group than in the acupuncture group (P<0.05). Conclusion Wheat-grain size cone moxibustion plus acupuncture can markedly improve the clinical symptoms of carpal tunnel syndrome. Its mechanism of action is related to reducing the cross-sectional area and edema of the median nerve.

Comparison of Aspirin and Naoxintong Capsule () with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism.</p><p><b>METHODS</b>A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHADS-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year.</p><p><b>RESULTS</b>Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028).</p><p><b>CONCLUSIONS</b>Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).</p>

Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia.

BACKGROUND: Emerging evidence indicates that nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of PD. Tenuigenin, a major active component of Polygala tenuifolia, has been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. METHODS: In the present study, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was established to explore the effect of tenuigenin on dopaminergic neurons in substantia nigra. We next activated NLRP3 inflammasome in both BV2 microglia cells and adult mice to investigate the mechanisms for the neuroprotective effect of tenuigenin. RESULTS: We demonstrated that treatment with tenuigenin increased striatal dopaminergic levels and improved motor impairment induced by MPTP. Also, tenuigenin significantly ameliorated the degeneration of dopaminergic neurons and inhibited NLRP3 inflammasome activation in substantia nigra of MPTP mouse model. We further found that tenuigenin reduced intracellular reactive oxygen species (ROS) production and suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1ß secretion in BV2 microglia cells. These data indicate that tenuigenin inhibits the activation of NLRP3 inflammasome via downregulating ROS. Correspondingly, in vivo data showed that tenuigenin attenuates microglia activation induced by lipopolysaccharide (LPS) in substantia nigra via suppressing NLRP3 inflammasome. CONCLUSIONS: Our findings reveal that tenuigenin protects dopaminergic neurons from inflammation partly through inhibition of NLRP3 inflammasome activation in microglia, and suggest the promising clinical use of tenuigenin for PD therapy.

Retrieval of Au, Ag, Cu precious metals coupled with electric energy production via an unconventional coupled redox fuel cell reactor.

The recovery of heavy metals from aqueous solutions or e-wastes is of upmost importance. Retrieval of Au, Ag, and Cu with electricity generation through building an ethanol-metal coupled redox fuel cells (CRFCs) is demonstrated. The cell was uniquely assembled on PdNi/C anode the electro-oxidation of ethanol takes place to give electrons and then go through the external circuit reducing metal ions to metallic on the cathode, metals are recovered. Taking an example of removal of 100mgL-1 gold in 0.5M HAc-NaAc buffer solution as the catholyte, 2.0M ethanol in 1.0M alkaline solution as the anolyte, an open circuit voltage of 1.4V, more than 96% of gold removal efficiency in 20h, and equivalent energy production of 2.0kWhkg-1 of gold can be readily achieved in this system. When gold and copper ions coexist, it was confirmed that metallic Cu is formed on the cathodic electrode later than metallic Au formation by XPS analysis. Thus, this system can achieve step by step electrodeposition of gold and copper while the two metal ions coexisting. This work develops a new approach to retrieve valuable metals from aqueous solution or e-wastes.

The pulmonary toxicity study of nano-silica particles on rats through dynamic inhalation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the pulmonary toxicity of different concentrations of nano-silica (nano-SiO2) under continuous dynamic inhalation conditions in the rat.</p><p><b>METHODS</b>48 male Sprague-Dawley rats were randomly divided into four groups, including the dispersant control group (saline) and nano-SiO2 low-dose group (0.3%, w/v), the middle-dose group (1%) and the high-dose group (3%). Animals were sacrificed at 28 d after exposure under continuous dynamic inhalation conditions, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. And following items were observed: body coefficient, BALF related items (leukocytes and classification, total protein content, LDH activity), lung tissue pathological changes (HE staining), and pulmonary fibrosis forming (collagen fiber VG staining).</p><p><b>RESULTS</b>Compared to the dispersant control group, there was no significant change on lung organ coefficient in Nano-SiO2 group (P < 0.05). The BALF total WBC count in 1% and 3% in nano-SiO2 groups showed higher value than the dispersant control group (P < 0.05). No obvious changes were found on total protein content and LDH activity in nano-SiO2 groups compared to the dispersant control group (P > 0.05). For differential WBC counts, lymphocyte count in BALF in nano-SiO2 groups was significantly decreased (P < 0.05), monocyte and macrophage counts were significantly increased (P < 0.05), but there was no difference on the proportion of neutrophils (P > 0.05). HE staining results showed that the obvious thickening of alveolar wall in nano-SiO2 groups, inflammatory cell infiltration also increased around the bronchial and vascular wall. Lung fibrosis VG staining showed no significant change of collagen fiber distribution.</p><p><b>CONCLUSION</b>Under our experimental conditions, the continuous dynamic inhalation of nano-SiO2 only caused the significant inflammation in rat lungs, pulmonary fibrosis phenomenon could not be observed significantly.</p>

Ctriporin, a new anti-methicillin-resistant Staphylococcus aureus peptide from the venom of the scorpion Chaerilus tricostatus.

Antibiotic-resistant microbes, such as methicillin-resistant Staphylococcus aureus, seriously threaten human health. The outbreak of "superbugs" in recent years emphasizes once again the need for the development of new antimicrobial agents or resources. Antimicrobial peptides have an evident bactericidal effect against multidrug-resistant pathogens. In the present study, a new antimicrobial peptide, ctriporin, was cloned and characterized from the venom of the scorpion Chaerilus tricostatus, an animal which has not yet been explored for toxic peptide resources. The MICs of ctriporin against Staphylococcus aureus, Bacillus thuringiensis, Bacillus subtilis, Micrococcus luteus, and Candida albicans are 5 to 20 µg/ml. Meanwhile, it MIC against clinical antibiotic-resistant bacterial strains is 10 µg/ml. Furthermore, the potential for ctriporin to be used as a topical antibiotic for treating staphylococcal skin infections was investigated. External use of the peptide ctriporin dramatically decreased the bacterial counts and cured skin infections in mice. In addition, ctriporin demonstrates antimicrobial efficacy via the bactericidal mechanism of rapid cell lysis. Together, these results suggest the potential of developing ctriporin as a new topical antibiotic.

Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine.

Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. The present aim was to observe the effects of sodium caprate on the intestinal absorption and antidiabetic action of berberine. The in situ, in vitro, and in vivo models were used to observe the effect of sodium caprate on the intestinal absorption of berberine. Intestinal mucosa morphology was measured to evaluate the toxic effect of sodium caprate. Diabetic model was used to evaluate antidiabetic effect of berberine coadministered with sodium caprate. The results showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. Sodium caprate stimulated mucosal-to-serosal transport of berberine; the enhancement ratios were 2.08, 1.49, and 3.49 in the duodenum, jejunum, and ileum, respectively. After coadministration, the area under the plasma concentration-time curve of berberine was increased 28% than that in the absence of sodium caprate. Furthermore, both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats (P < 0.05). The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group (P < 0.05). Morphologic analysis indicated that sodium caprate was not significantly injurious to the intestinal mucosa. The study demonstrates that sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

Direct regulation of BK channels by phosphatidylinositol 4,5-bisphosphate as a novel signaling pathway.

Large conductance, calcium- and voltage-gated potassium (BK) channels are ubiquitous and critical for neuronal function, immunity, and smooth muscle contractility. BK channels are thought to be regulated by phosphatidylinositol 4,5-bisphosphate (PIP(2)) only through phospholipase C (PLC)-generated PIP(2) metabolites that target Ca(2+) stores and protein kinase C and, eventually, the BK channel. Here, we report that PIP(2) activates BK channels independently of PIP(2) metabolites. PIP(2) enhances Ca(2+)-driven gating and alters both open and closed channel distributions without affecting voltage gating and unitary conductance. Recovery from activation was strongly dependent on PIP(2) acyl chain length, with channels exposed to water-soluble diC4 and diC8 showing much faster recovery than those exposed to PIP(2) (diC16). The PIP(2)-channel interaction requires negative charge and the inositol moiety in the phospholipid headgroup, and the sequence RKK in the S6-S7 cytosolic linker of the BK channel-forming (cbv1) subunit. PIP(2)-induced activation is drastically potentiated by accessory beta(1) (but not beta(4)) channel subunits. Moreover, PIP(2) robustly activates BK channels in vascular myocytes, where beta(1) subunits are abundantly expressed, but not in skeletal myocytes, where these subunits are barely detectable. These data demonstrate that the final PIP(2) effect is determined by channel accessory subunits, and such mechanism is subunit specific. In HEK293 cells, cotransfection of cbv1+beta(1) and PI4-kinaseIIalpha robustly activates BK channels, suggesting a role for endogenous PIP(2) in modulating channel activity. Indeed, in membrane patches excised from vascular myocytes, BK channel activity runs down and Mg-ATP recovers it, this recovery being abolished by PIP(2) antibodies applied to the cytosolic membrane surface. Moreover, in intact arterial myocytes under physiological conditions, PLC inhibition on top of blockade of downstream signaling leads to drastic BK channel activation. Finally, pharmacological treatment that raises PIP(2) levels and activates BK channels dilates de-endothelized arteries that regulate cerebral blood flow. These data indicate that endogenous PIP(2) directly activates vascular myocyte BK channels to control vascular tone.

Human pregnane X receptor-mediated transcriptional regulation of cytochrome P450 3A4 by some phytochemicals / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To test the effect on human pregnane X receptor (hPXR)-mediated transcription regulation of CYP3A4 by five selected phytochemicals.</p><p><b>METHODS</b>Transient cotransfection reporter gene assays in HepG(2) cells were performed with the hPXR expression plasmid and the reporter gene plasmid which contains XRE in the promoter of CYP3A4 linked to luciferase.</p><p><b>RESULTS</b>In the dose-effect study, soybean isoflavone, luteolin and curcumin induced the CYP3A4 transcription via PXR in an evident dose-dependent manner, but isorhamnetin and rutin did not. The inducibility of soybean isoflavone, luteolin and curcumin was also increased in concentrations between 1 micromol/L and 50 micromol/L, 24 h after induction, 50 micromol/L soybean isoflavone, luteolin and curcumin exhibited a 5.46-fold, 2.87-fold, and 2.07-fold increase respectively, compared with 0.1% DMSO treated cells. In the time-effect study, 10 micromol/L and 50 micromol/L soybean isoflavone, luteolin and curcumin induced CYP3A4 transcription between 12 h and 48 h, the strongest induction appeared in 48 h. 48 h after induction, 50 micromol/L soybean isoflavone, luteolin and curcumin exhibited a 6.72-fold, 3.24-fold, and 2.13-fold increase respectively, compared with 0.1% DMSO treated cells.</p><p><b>CONCLUSION</b>Three phytochemicals, i.e. soybean isoflavone, luteolin and curcumin stimulate the PXR-mediated transcription of CYP3A4. Isorhamnetin and rutin have no effect on the CYP3A4 transcription via PXR.</p>