Cold and Heat in Acute Coronary Syndrome： A Review / 中国实验方剂学杂志

Cold and heat belong to the eight-principal syndrome differentiation of traditional Chinese medicine， which can reflect the rise and fall of Yin and Yang in the body and the Yin and Yang nature of the disease. At present， traditional Chinese medicine has an inconsistent understanding of cold and heat in acute coronary syndrome. The emphasis on pathogenic factors of cold and heat is biased， and the elements of cold and heat syndrome are not fully reflected in the scale. Therefore， the literature has been reviewed from the perspectives of etiology， pathogenesis， symptom elements， and test signs with drugs. From the perspective of etiology， both cold evil and heat evil can increase the risk of acute coronary syndrome. It was previously believed that acute coronary syndrome occurs frequently in cold climates such as winter and spring. Based on this understanding， hot weather can also induce acute coronary syndrome， and different temperatures have different effects on patients of different ages and with different underlying diseases. In addition， artificial pathogenic factors such as excessive consumption of cold food and refrigeration air conditioners were added. From the perspective of pathogenesis， on the basis of the traditional ''asthenia in origin and asthenia in superficiality'' and ''phlegm stagnation''， it is found that Yin-cold and fire-heat can both cause paralysis of the heart chakra and pain induced by the blockage. The pathogenesis of acute coronary syndrome characterized by heat stagnation and coldness featuring heartburn should be distinguished from gastroesophageal reflux disease. Moreover， the pathogenesis of Yin cold coagulation and pulse stagnation and wind obstruction are different. The acute coronary syndrome is in line with the wind characteristics of frequent changes and can be treated with wind medicine. From the perspective of syndrome elements， the syndrome elements such as cold condensation， heat accumulation， and toxicity are analyzed， and the use of basic syndrome elements and their combination forms facilitates clinical and scientific research. In addition， according to the test sign with the drug， it can be seen that the attributes of cold and heat of traditional Chinese medicine prescriptions for acute coronary syndrome can be explained according to the temperature-sensitive transient receptor potential （TRP） ion channel， thus proving the pathogenesis of cold and heat of acute coronary syndrome.

Research progress of TRPV4 in ocular pathophysiological function / 国际眼科杂志(Guoji Yanke Zazhi)

Transient receptor potential vanilloid receptor 4(TRPV4)is a non-selective cation channel responsible for sensing changes in cell swelling, temperature, mechanical stretch, shear stress and osmotic pressure by regulating transmembrane calcium signaling and thereby influencing gene expression, cell morphology, and cytoskeletal construction. TRPV4 is widely expressed throughout the body. Intraocularly, TRPV4 is functionally expressed in the cornea, lens, ciliary body, trabecular meshwork and retina. In this article, the expression and physiopathological functions of TRPV4 in various tissues of the eye were described. With the in-depth study of TRPV4 in ocular pathophysiological functions, TRPV4 may become a potential drug target in corneal injury repair, glaucoma and retinal angiogenesis, but further in-depth study is still needed.

The mechanism of chlorogenic acid against neuropathic pain induced by cisplatin / 药学学报

This study aimed to investigate the analgesic effect of chlorogenic acid on cisplatin-induced neuropathic pain and explored the underlying molecular mechanisms. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Xinxiang Central Hospital, in compliance with the Institutional Animal Care Guidelines. Von Frey hair and a radiant heat was employed to measure mechanical allodynia and thermal hyperalgesia; Western blot was used to examine transient receptor potential vanilloid type-1 (TRPV1) protein expression in the rat dorsal root ganglion (DRG); patch clamp was used to record TRPV1 currents in DRG neurons. The experimental results showed that chlorogenic acid could attenuate cisplatin-induce mechanical allodynia and thermal hyperalgesia in rats. The expression of TRPV1 protein in DRGs was increased in cisplatin-treated rats, while chlorogenic acid also could reverse cisplatin-induced the upregulation of TRPV1 protein. Forthermore, chlorogenic acid could attenuate cisplatin-mediated the upregulation of TRPV1 current density. These above results indicated that chlorogenic acid could alleviate cisplatin-induced pain hypersensitivity through inhibition of the expression and function of TRPV1 in rats.

Mechanism of Zhishi Xiebai Guizhitang in Treating AS Based on Regulation of Cholesterol Metabolism in Foam Cells by TRPA1 / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg-1） and simvastatin group （0.002 g·kg-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension in mice and its mechanism / 中国药理学通报

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

Measurement of optic nerve sheath diameter on computed tomography for the differentiation of transient ischemic attacks

SUMMARY OBJECTIVE: The objective of this study was to investigate whether the measurement of mean optic nerve sheath diameter in patients with transient ischemic attack could be used to distinguish between control groups, the acute ischemic stroke group, and subgroups within the acute ischemic stroke category. METHODS: Retrospectively, the mean optic nerve sheath diameters of patients aged 18 years and older belonging to control, transient ischemic attack, acute ischemic stroke, and subgroups within the acute ischemic stroke category were measured with initial computed tomography conducted in the emergency department. RESULTS: Out of the 773 patients included in the study, 318 (41.1%) were in the control group, 77 (10%) had transient ischemic attack, and 378 (49%) were categorized as stroke patients. The average mean optic nerve sheath diameter was significantly higher in both the stroke and transient ischemic attack groups compared with the control group (p<0.001 for both comparisons). Furthermore, the mean optic nerve sheath diameter in the stroke subgroups was significantly higher than in both the transient ischemic attack and control groups (p<0.001 for all comparisons). In transient ischemic attack patients, the mean optic nerve sheath diameter showed a significant ability to predict transient ischemic attack (AUC=0.913, p<0.001), with a calculated optimal cutoff value of 4.72, sensitivity of 94.8%, and specificity of 73.9%. CONCLUSION: The mean optic nerve sheath diameter of patients in the transient ischemic attack group was lower compared with those in the stroke subgroups but higher compared with the control group.

TRANSIENT STRUCTURES FOR STREET VENDORS: VIABLE DESIGN INTERVENTIONS

The commercial sector in India is ever-changing with a visible divide in different aspects of the operations, this leads to the creation of different sectors of the economy namely the 'formal' and the 'informal sector'. There is a wide disparity in documentation and assessment needs of the commercial setups involved in different types of activities in such 'unorganized' or 'informal' units. The Government of NCT of Delhi data on street vendors indicates that Delhi has an estimate of over 4 lakh vendors who are working in the informal sector as street vendors, roadside tea sellers, small roadside nursery owners, etc. all these setups require a special type of planning & consideration as these vendors have limited resource availability, with many of these street vendors finding accommodations in their mobile carts, and unplanned roadside setups. The state of livelihood and resource access remains limited for these 'informal' vendors. Issues such as the access to 'safe' infrastructure, permits & certification to operate as street vendors limit their social and economic well-being. Such concerns require significant social and design interventions to ensure the social, physical, and economic well-being of the vendors on 'the streets'.

Nutritional Vulnerability Transitions among Rural Households in Nigeria

Aims: It has long been considered that specific age/gender groups, such as women and children, are predisposed to nutritional vulnerability. Thus, nutritional vulnerability among agricultural households is neglected and understudied. This study aims at an empirical assessment of nutritional vulnerability dynamics among rural households in Nigeria. Study Design: Secondary data used for this study was waves 2 and 3 of the general household survey panel data. The sampling design consisted of two stages of sampling: the selection of enumeration areas based on probability proportionate to the size of the enumeration areas and the systematic random selection of ten households from each enumeration area. There were 3370 households selected in rural areas and 1630 households selected in urban areas. 2090 rural households with the required information for this study were included in the analysis. Methodology: Descriptive statistics, nutritional vulnerability score, logit regression model, Markov model, and multinomial logit regression models were used to analyse nutritional vulnerability transitions among rural households in Nigeria. Results: Nutritionally vulnerable households in rural Nigeria include those with aged heads, little or no formal education, limited assets, and no access to land or credit. Nutritional vulnerability in rural Nigeria is primarily transient, with around two-fifths of households experiencing transient nutritional vulnerability and nearly one-third experiencing chronic nutritional vulnerability. While the age of the household head, tertiary education, and access to credit all had a substantial impact on transient nutritional vulnerability, gender, tertiary education, asset value, and access to credit all had an impact on chronic nutritional vulnerability. Conclusion: Support mechanisms such as initiatives to promote access to healthy food, credit, land, and education are critical. To successfully address the issues affecting the nutrition and health of persons facing vulnerabilities, social welfare programs with interventions based on the characteristics of each vulnerable group and the predisposing factors should be adopted.

Amyloid spell – A close mimic of transient ischemic attack!

Transient focal neurological episodes, also called amyloid spells occur as recurrent, transient episodes of spreading paresthesia seen in 14% of cerebral amyloid angiopathy (CAA) patients. An 81-year-old gentleman with coronary artery disease and a left ventricular clot was on anticoagulant treatment. He presented with three episodes of tingling in the left fingers spreading to the left arm and left leg, each lasting for 10 min. Magnetic resonance imaging of the brain with susceptibility imaging showed convexity hemorrhage, and curvilinear blooming in sulcal spaces of the right cerebral convexity and left precuneus. Warfarin was stopped. He was treated with clobazam, aspirin, and atorvastatin. He improved, so was discharged after 2 days. Amyloid spells can be confused with transient ischemic attack (TIA) or its mimics and the treatment given for TIA can lead to intracranial hemorrhage in CAA patients. Radiological features aid in the diagnosis of CAA and antiplatelets need to be administered cautiously in patients with suspected TIA.

Influencing factors of intracranial in-stent restenosis / 国际脑血管病杂志

Intracranial atherosclerotic stenosis (ICAS) is the main cause of ischemic stroke. Endovascular therapy (EVT) is a method of treating symptomatic ICAS, and in-stent restenosis (ISR) is an important factor affecting the efficacy of EVT. This article summarizes the influencing factors of ISR in patients with ICAS receiving EVT treatment.

Encephalo-duro-arterio-synangiosis for intracranial arterial steno-occlusive disease: a retrospective case series study of 40 cases / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of encephalo-duro-arterio-synangiosis (EDAS) for intracranial atherosclerotic steno-occlusive disease (ICASD).Methods:Patients with symptomatic ICASD received EDAS treatment in the Department of Neurosurgery, the PLA General Hospital from January 2018 to January 2019 were retrospectively included. The baseline information, perioperative complications, primary endpoint events, and changes in modified Rankin Scale (mRS) scores before and after surgery were collected. The primary endpoint event was any stroke/death that occurred within 30 d after enrollment. The secondary endpoint events were any stroke/death, non-stroke bleeding (subdural or epidural bleeding), and clinical functional improvement after 30 d. The clinical functional improvement was defined as a decrease of ≥1 in the mRS score compared to before surgery.Results:A total of 40 patients were included, including 30 males and 10 females, aged 53.9±8.6 years old. The clinical symptoms were mainly limb weakness and dizziness. One case of ischemic stroke and one case of hemorrhagic stroke occurred during the perioperative period. The primary endpoint event incidence was 2.5%. The patients were followed up for 49.75±2.99 months after surgery. One patient died of cerebral hemorrhage 31 months after surgery, and one patient developed acute ischemic stroke 35 months after surgery. The postoperative mRS scores of 34 patients decreased compared to before surgery, and the clinical function improvement rate was 85%. The mRS score increased in 2 cases after surgery compared to before surgery and 4 cases had no change.Conclusion:EDAS can improve the clinical function of patients with symptomatic ICASD and reduce the incidence of long-term stroke.

Traditional Chinese Medicine Intervenes in Atherosclerosis by Regulating TLR/NLRP3 Pathway via TRPV1/TRPA1 / 中国实验方剂学杂志

Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.

Role of transient receptor potential channels in melanocytes and their related diseases / 中华皮肤科杂志

Transient receptor potential (TRP) channels are a special type of non-selective cationic channel family located on the cell membrane or organelle membrane, and notably expressed in melanocytes. This review summarizes recent research progress in biological functions of TRP channels in melanocytes and their involvement in the pathological process of pigmented skin diseases and melanoma, so as to provide a new theoretical basis for the prevention and treatment of melanin-related diseases.

Diagnostic value of serum uric acid combined with high-density lipoprotein cholesterol for nonalcoholic fatty liver disease in health examination population / 中华健康管理学杂志

Objective:To assess the value of serum uric acid combined with high-density lipoprotein cholesterol (HDL-C) for the diagnosis of nonalcoholic fatty liver disease (NAFLD) in health examination population.Methods:A cross-sectional study was conducted. Total of 3 903 subjects who underwent health examination in the health management center of the First Affiliated Hospital of Zhejiang University School of Medicine from January to November 2022 were retrospectively selected for this study. The demography and somatology examination, laboratory tests and transient elastography of the liver were carried out in all the subjects. The indices were compared in people with and without NAFLD with t test, single factor analysis of variance or Wilcoxon rank sum test. And the levels of uric acid and HDL-C under different degrees of fatty liver were analyzed. The diagnostic value of uric acid combined with HDL-C for NAFLD was examined with the receiver operator characteristic (ROC) curve and area under the ROC curve (AUC). Results:Body mass index, uric acid and glutathione transaminase in the NAFLD group were all higher than those in the non-NAFLD group, and HDL-C was lower (all P<0.001). Blood uric acid in normal liver group (303.62±77.65) μmol/L <mild fatty liver group (336.82±82.43) μmol/L <moderate fatty liver group (364.25±79.62) μmol/L <severe fatty liver group (392.98±83.90) μmol/L ( F=202.614, P<0.001); HLD-C in normal liver group (1.43±0.37) mmol/L >mild fatty liver group (1.25±0.31) mmol/L >moderate fatty liver group (1.16±0.28) mmol/L >severe fatty liver group (1.04±0.25) mmol/L ( F=239.24, P<0.001).The proportion of NAFLD in hyperuricemia group (HUA group) (75.0%), low HDL-C group (76.3%), and HUA and low HDL-C group (86.9%) was significantly higher than that in normal uric acid and HDL-C groups (49.2%), and the proportion of NAFLD in HUA and low HDL-C group was the highest ( χ 2=302.109, P<0.001). The diagnostic value of the combination of serum uric acid and HDL-C for NAFLD is higher than that of serum uric acid or HDL-C alone (the AUC was 0.741, 0.692 and 0.288, respectively) (both P<0.001). Conclusion:Serumuric acid and HDL-C were correlated with the severity of NAFLD, and uric acid combined with HDL-C had some diagnostic value for NAFLD.

Mechanism of Renshentang in Treatment of Atherosclerosis Based on Autophagic Effect of TRPV1 on Arterial Smooth Muscle / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Renshentang， recorded in Synopsis of Golden Chamber， in the treatment of atherosclerosis （AS） based on the autophagic effect of transient receptor potential vanilloid subtype 1 （TRPV1） on arterial smooth muscle. MethodFourteen SPF-grade 8-week-old male C57BL/6J mice were assigned to the normal group and 70 8-week-old apolipoprotein E knockout （ApoE-/-） mice were assigned to the experimental group. The AS model was induced by a high-fat diet in the mice in the experimental group for eight weeks. The model mice were then randomly divided into model group， low-， medium-， and high-dose Renshentang groups （2.715， 5.43， and 10.68 g·kg-1·d-1）， and simvastatin group （0.02 g·kg-1·d-1）. Drug treatment lasted eight weeks. Serum was taken and serum total cholesterol （CHO）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured by assay kits to observe the changes in lipid levels in mice. The aorta was stained with hematoxylin-eosin （HE） to observe the overall pathology of the aortic root and oil red O staining was used to detect the lipid deposition in the aortic plaque and calculate the percentage of the aortic root area to the lumen area. The protein expression of TRPV1， adenylate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， autophagy effector-1 （Beclin-1）， and microtubule-associated protein 1 light chain 3 （LC3Ⅱ） in mouse aortic tissues was determined by Western blot. ResultCompared with the normal group， the model group showed increased serum CHO， TG， and LDL-C levels， decreased HDL-C， and increased aortic root plaque area （P<0.01）. Compared with the model group， the Renshentang groups showed decreased levels of CHO， TG， and LDL-C in serum （P<0.05， P<0.01）， especially in the low- and medium-dose Renshentang groups （P<0.01）. Compared with the normal group， the simvastatin group and the Renshentang groups showed reduced aortic root plaque area （P<0.05）， especially in the high-dose Renshentang group （P<0.01）. Compared with the normal group， the model group showed decreased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Renshentang groups showed increased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（P<0.05，P<0.01）. ConclusionThe anti-AS effect of Renshentang recorded in Synopsis of Golden Chamber may be achieved by up-regulating TRPV1 expression to restore the level of autophagy mediated by AMPK.

Protective role and mechanism of human umbilical cord mesenchymal stem cell-derived exosome in renal ischemia-reperfusion injury / 器官移植

Objective To investigate the protective effect of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI), and to clarify the critical role and regulating mechanism of transient receptor potential canonical (TRPC) 6/poly adenosine-diphosphate-ribose polymerase (PARP) 1 signaling pathway during this process. Methods The hucMSC-Exo was extracted by ultracentrifugation, and identified by transmission electron microscope (TEM), nanoparticle tracing analysis and Western blot. SD rats were randomly divided into the sham operation group (group S), sham operation+TRPC6 inhibitor SKF96365 group (group SS), renal IRI group (group IRI), exosome treatment group (group EXO) and exosome +TRPC6 inhibitor SKF96365 group (group ES), with 6 rats in each group. Serum creatinine and blood urea nitrogen levels were detected. Pathological changes of renal tissues were observed by hematoxylin-eosin (HE) staining and Paller score was calculated. The expression levels of key molecules of necroptosis in rat renal tissues, including receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed-lineage kinase domain-like protein (MLKL), TRPC6 and PARP1, were detected by Western blot. Results Typical saucer-like structure was observed under TEM. Nanoparticle tracing analysis showed that the average diameter of the extracted substance was 125.9 nm. Western blot revealed that the surface markers of CD9, CD63 and CD81 were positively expressed, confirmed that the extracted substance was exosome. Compared with group S, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was worsened, Paller score was elevated, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group IRI (all P < 0.05). Compared with group IRI, the serum creatinine and blood urea nitrogen levels were down-regulated, the pathological damage of renal tissues was mitigated, Paller score was decreased, the relative expression levels of TRPC6 and PARP1 proteins were up-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were down-regulated in group EXO (all P < 0.05). Compared with group EXO, the serum creatinine and blood urea nitrogen levels were up-regulated, the pathological damage of renal tissues was aggravated, Paller score was increased, the relative expression levels of TRPC6 and PARP1 proteins were down-regulated, and the relative expression levels of RIPK1, RIPK3 and MLKL proteins were up-regulated in group ES (all P < 0.05). Conclusions hucMSC-Exo may alleviate the necroptosis induced by renal IRI in rat models, which is related to the activation of TRPC6/PARP1 signaling pathway.

Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels / 中国中药杂志

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Improvement effect of diterpene ginkgolides on acute tMCAO rats and chronic tMCAO rats / 药学学报

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

Inhibitory effects of a TRPM4 inhibitor 9-phenanthrol on electrical activity of INS-1 pancreatic β-cells / 药学学报

The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel expressed in pancreatic β-cells is implicated in the β-cell function and insulin secretion, but how pharmacological function of TRPM4 channel affects membrane excitability of β-cells remains largely unknown. Here, we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreatic β-cells. In whole-cell current clamp recordings, 9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreatic β-cells in a dose-dependent manner with an IC50 value of 14.99 ± 7.93 μmol·L-1. Similarly, 9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection. Further recordings of β-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol. Taken together, our results show the involvement of TRPM4 channel function in pancreatic β-cells depolarization and action potential, it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreatic β-cells.

Research progress of TRPV4 in glaucoma optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucomatous optic neuropathy(GON)is the difficulty of glaucoma treatment. In recent years, a variety of theories have been put forward about the pathogenesis of GON, but none of them can explain the principle of optic neuropathy caused by all types of glaucoma, which makes the disease difficult to treat in clinical treatment and is not conducive to early intervention. The latest research found that the transient receptor potential channel vanillic acid subfamily 4(TRPV4)in the retina plays an important role in various pathogenesis of GON. This article will review TRPV4 and its role in the occurrence and development of GON in order to find a common “connection point” for the multiple mechanism theories of GON, which will contribute to further understanding and clinical treatment of the disease.