TRIM64 promotes ox-LDL-induced foam cell formation, pyroptosis, and inflammation in THP-1-derived macrophages by activating a feedback loop with NF-κB via IκBα ubiquitination.

Atherosclerosis is a chronic inflammatory disease and the main pathology behind most cardiovascular diseases and the overactivation of macrophages initiates the development of atherosclerosis. However, the specific functions of oxidized low-density lipoprotein (ox-LDL) in macrophages remain elusive. Macrophages derived from monocyte (THP-1) were treated with ox-LDL and were used to generate atherosclerosis in an in vitro model. NLRP3 inflammasome markers were examined using quantitative RT-PCR and Western blotting. Cytokines were measured using ELISA. Chromatin immunoprecipitation (ChIP) was utilized to detect nuclear factor kappa B (NF-κB) and TRIM64 interactions. A fat-rich diet was applied to ApoE-/- mice for in vivo studies. ox-LDL promoted TRIM64 expression in a time-dependent manner. According to loss- and gain-of-function analyses, TRIM64 enhanced the activation of NLRP3 inflammasomes and the expression of downstream molecules. TRIM64 directly interacted with IκBα and promoted IκBα ubiquitination at K67 to activate NF-κB signaling. We detected direct binding between NF-κB and the TRIM64 promoter, as well as enhanced TRIM64 expression. Our study revealed an interaction between TRIM64 and NF-κB in the development of atherosclerosis. TRIM64 and NF-κB formed a positive feedback to activate NF-κB pathway. ox-LDL induces foam cell formation and TRIM64 expression TRIM64 regulates ox-LDL-induced foam cell formation, pyroptosis and inflammation via the NF-κB signaling TRIM64 activates NF-κB signaling by ubiquitination of IκBα NF-κB inhibition attenuates atherosclerosis in HFD-induced ApoE (-/-) mice.

Network Pharmacology Analysis to Identify Phytochemicals in Traditional Chinese Medicines That May Regulate ACE2 for the Treatment of COVID-19.

"Three formulas and three medicines," which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, Qingfei Paidu decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, have been proven to be effective in curbing coronavirus disease 2019 (COVID-19), according to the State Administration of Traditional Chinese Medicine. The aims of this study were to identify the active components of "Three formulas and three medicines" that can be used to treat COVID-19, determine their mechanism of action via angiotensin-converting enzyme 2 (ACE2) by integrating network pharmacological approaches, and confirm the most effective components for COVID-19 treatment or prevention. We investigated all the compounds present in the aforementioned herbal ingredients. Compounds that could downregulate the transcription factors (TFs) of ACE2 and upregulate miRNAs of ACE2 were screened via a network pharmacology approach. Hepatocyte nuclear factor 4 alpha (HNF4A), peroxisome proliferator-activated receptor gamma (PPARG), hsa-miR-2113, and hsa-miR-421 were found to regulate ACE2. Several compounds, such as quercetin, decreased ACE2 expression by regulating the aforementioned TFs or miRNAs. After comparison with the compounds present in Glycyrrhiza Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to search for possible molecular mechanisms of these compounds. In conclusion, traditional Chinese medicine (TCM) plays a pivotal role in the prevention and treatment of COVID-19. Quercetin, glabridin, and gallic acid, the active components of recommended TCM formulas and medicines, can inhibit COVID-19 by downregulating ACE2.

The effects of renin-angiotensin system inhibitors (RASI) in coronavirus disease (COVID-19) with hypertension: A retrospective, single-center trial.

INTRODUCTION AND OBJECTIVE: A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. PATIENTS AND METHOD: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. RESULTS: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. CONCLUSIONS: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms.

INTRODUCCIÓN Y OBJETIVO: Un reciente brote de la enfermedad coronavirus 2019 (COVID-19) se produce en todo el mundo. La enzima convertidora de angiotensina 2 (ACE2) puede mediar la entrada del coronavirus en las células huésped. Por lo tanto, se sospechaba que los inhibidores del sistema renina-angiotensina (SRA) contribuían al aumento de la infección por coronavirus. Nos propusimos analizar los efectos de los SRA en los pacientes COVID-19 con hipertensión. PACIENTES Y MÉTODO: En este estudio retrospectivo, de un solo centro, se analizaron 27 pacientes de COVID-19 con hipertensión, que fueron admitidos en el Centro Clínico de Salud Pública de Shangai desde el 25 de enero de 2020 hasta el 31 de enero de 2020, para determinar las características clínicas, los parámetros de laboratorio, los medicamentos y la duración de la estancia. A todos los pacientes se les administró un tratamiento antiviral y antihipertensivo, de los cuales 14 pacientes fueron tratados con SRA y 13 sin SRA. RESULTADOS: Comparando los dos grupos, no encontramos diferencias estadísticamente significativas en los síntomas clínicos y las pruebas de laboratorio. Además, la tos no se agravó. CONCLUSIONES: A través del análisis de esta pequeña muestra, el SRA podría considerarse seguro y eficaz para controlar la presión arterial alta de los pacientes con COVID-19. Es necesario realizar más análisis con una muestra de mayor tamaño para explorar los mecanismos subyacentes.

The effects of renin-angiotensin system inhibitors (RASI) in coronavirus disease (COVID-19) with hypertension: A retrospective, single-center trial / Efecto de los inhibidores del sistema renina-angiotensina en la infección Covid-19. Estudio retrospectivo unicéntrico

INTRODUCTION AND OBJECTIVE: A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin–angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. PATIENTS AND METHOD: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. RESULTS: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. CONCLUSIONS: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanism

INTRODUCCIÓN Y OBJETIVO: Un reciente brote de la enfermedad coronavirus 2019 (COVID-19) se produce en todo el mundo. La enzima convertidora de angiotensina 2 (ACE2) puede mediar la entrada del coronavirus en las células huésped. Por lo tanto, se sospechaba que los inhibidores del sistema renina-angiotensina (SRA) contribuían al aumento de la infección por coronavirus. Nos propusimos analizar los efectos de los SRA en los pacientes COVID-19 con hipertensión. PACIENTES Y MÉTODO: En este estudio retrospectivo, de un solo centro, se analizaron 27 pacientes de COVID-19 con hipertensión, que fueron admitidos en el Centro Clínico de Salud Pública de Shangai desde el 25 de enero de 2020 hasta el 31 de enero de 2020, para determinar las características clínicas, los parámetros de laboratorio, los medicamentos y la duración de la estancia. A todos los pacientes se les administró un tratamiento antiviral y antihipertensivo, de los cuales 14 pacientes fueron tratados con SRA y 13 sin SRA. RESULTADOS: Comparando los dos grupos, no encontramos diferencias estadísticamente significativas en los síntomas clínicos y las pruebas de laboratorio. Además, la tos no se agravó. CONCLUSIONES: A través del análisis de esta pequeña muestra, el SRA podría considerarse seguro y eficaz para controlar la presión arterial alta de los pacientes con COVID-19. Es necesario realizar más análisis con una muestra de mayor tamaño para explorar los mecanismos subyacentes

The effects of renin-angiotensin system inhibitors (RASI) in coronavirus disease (COVID-19) with hypertension: A retrospective, single-center trial.

INTRODUCTION AND OBJECTIVE: A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. PATIENTS AND METHOD: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. RESULTS: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. CONCLUSIONS: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms.

The effects of renin-angiotensin system inhibitors (RASI) in coronavirus disease (COVID-19) with hypertension: A retrospective, single-center trial / Efecto de los inhibidores del sistema renina-angiotensina en la infección Covid-19. Estudio retrospectivo unicéntrico

INTRODUCTION AND OBJECTIVE: A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. PATIENTS AND METHOD: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. RESULTS: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. CONCLUSIONS: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms

INTRODUCCIÓN Y OBJETIVO: Un reciente brote de la enfermedad coronavirus 2019 (COVID-19) se produce en todo el mundo. La enzima convertidora de angiotensina 2 (ACE2) puede mediar la entrada del coronavirus en las células huésped. Por lo tanto, se sospechaba que los inhibidores del sistema renina-angiotensina (SRA) contribuían al aumento de la infección por coronavirus. Nos propusimos analizar los efectos de los SRA en los pacientes COVID-19 con hipertensión. PACIENTES Y MÉTODO: En este estudio retrospectivo, de un solo centro, se analizaron 27 pacientes de COVID-19 con hipertensión, que fueron admitidos en el Centro Clínico de Salud Pública de Shangai desde el 25 de enero de 2020 hasta el 31 de enero de 2020, para determinar las características clínicas, los parámetros de laboratorio, los medicamentos y la duración de la estancia. A todos los pacientes se les administró un tratamiento antiviral y antihipertensivo, de los cuales 14 pacientes fueron tratados con SRA y 13 sin SRA. RESULTADOS: Comparando los dos grupos, no encontramos diferencias estadísticamente significativas en los síntomas clínicos y las pruebas de laboratorio. Además, la tos no se agravó. CONCLUSIONES: A través del análisis de esta pequeña muestra, el SRA podría considerarse seguro y eficaz para controlar la presión arterial alta de los pacientes con COVID-19. Es necesario realizar más análisis con una muestra de mayor tamaño para explorar los mecanismos subyacentes

Effects of early intravenous low-dose of metoprolol on cardiac sympathetic activities and electrophysiological properties in myocardial infarction heart.

This study observed the effects of early intravenous low-doses of metoprolol on cardiac sympathetic activities and electrophysiological properties in myocardial infarction (MI) dogs. Thirty two mongrel dogs with the first diagonal branch of the left anterior descending coronary artery ligated were randomly divided into three groups: The low-dose group was given metoprolol 0.6 mg/kg immediately by intravenous injection (n=12); the target-dose group was given metoprolol 1.6 mg/kg (n=12), and the control group was injected with normal saline at the same dose of the target-dose group (n=8). Norepinephrine (NE) and epinephrine (E) levels in the coronary sinus (CS) blood as well as the ventricular effective refractory period (ERP) were all measured during the experiments. We found that NE and E concentrations in the three groups were all increased compared with the previous measurement before ligation. ERP values after MI were significantly decreased in all three groups compared with the first measurements. The three groups all exhibited uneven shortness of ERP among different regions, with significant shortness in infarcted area. Furthermore, there was no difference between the low and target-dose of metoprolol in the reduction of regional ERP, and the same effect was also observed in induced arrhythmias. In conclusion, a lower dose of metoprolol performed similarly as target-dose in reducing the catecholamine concentrations in dogs with MI. Our study demonstrated that a lower dose of metoprolol may be reasonable compared with the target-dose in ß-blocker therapy due to similar effect and lower toxicity.

Formulation and statistical optimization of gastric floating alginate/oil/chitosan capsules loading procyanidins: in vitro and in vivo evaluations.

The aim of the present work was to develop gastric floating capsules containing oil-entrapped beads loading procyanidins. The floating beads were prepared by ionotropic gelation method using sodium alginate, CaCl2 and chitosan. The effect of three independent parameters (concentration of sodium alginate, CaCl2 and chitosan) on entrapment efficiency were analyzed by Box-Behnken design. The floating beads were evaluated for surface morphology, particle size, density, entrapment efficiency, buoyancy, release behavior in vitro and floating ability in vivo. The prepared beads were grossly spherical in shape and the mean size was approximately 1.54±0.17mm. The density was 0.97g/cm3. And the optimal conditions were as follows: concentration of sodium alginate, CaCl2 and chitosan were 33.75mg/mL, 9.84mg/mL and 9.05mg/mL, respectively. The optimized formulation showed entrapment efficiency of 88.84±1.04% within small error-value (0.65). The release mechanism of floating capsules followed Korsmeyer-Peppas model (r2=0.9902) with non-Fickian release. The gastric floating capsules exhibited 100% floating percentage in vitro and they could float on the top of gastric juice for 5h in vivo. Therefore, the floating capsules are able to prolong the gastroretentive delivery of procyanidins.

Aqueous two-phase assisted by ultrasound for the extraction of anthocyanins from Lycium ruthenicum Murr.

In this study, an efficient ultrasound-assisted aqueous two-phase extraction method was used for the extraction of anthocyanins from Lycium ruthenicum Murr. An ethanol/ammonium sulfate system was chosen for the aqueous two-phase system due to its fine partitioning and recycling behaviors. Single-factor experiments were conducted to determine the optimized composition of the system, and the response surface methodology was used for the further optimization of the ultrasound-assisted aqueous two-phase extraction. The optimal conditions were as follows: a salt concentration of 20%, an ethanol concentration of 25%, an extraction time of 33.7 min, an extraction temperature of 25°C, a liquid/solid ratio of 50:1 w/w, pH value of 3.98, and an ultrasound power of 600 W. Under the above conditions, the yields of anthocyanins reached 4.71 mg/g dry sample. For the further purification, D-101 resin was used, and the purity of anthocyanins reached 25.3%. In conclusion, ultrasound-assisted aqueous two-phase extraction was an efficient, ecofriendly, and economical method, and it may be a promising technique for extracting bioactive components from plants.

Danhong Promotes Angiogenesis in Diabetic Mice after Critical Limb Ischemia by Activation of CSE-H 2 S-VEGF Axis.

The aim of this paper is to investigate effect and mechanism of Danhong injection (DH) on angiogenesis in the diabetic hind limb ischemia mouse model. Thirty diabetic hind limb ischemic model mice and ten normal mice, established by intraperitoneal (i.p.) injection of streptozotocin (STZ) or PBS and ligation/excision of femoral artery, and then twenty diabetic hind limb ischemic model mice of all were evenly randomized to saline (control, n = 10) and DH i.p. injection (2 mL/kg weight for 7 days, n = 10) groups. Limb perfusion recovery and femoral blood hydrogen sulfide (H2S) and vessel regeneration and lower limb vascular endothelial growth factor (VEGF)/cystathionine γ-lyase (CSE) expression were evaluated during intervention and after euthanasia, respectively. DH i.p. increased ischemic limb perfusion and promoted collateral circulation generation without decreasing blood glucose level. Increased local CSE-H2S-VEGF expression contributed to beneficial effects of DH injection. In conclusion, activation of local CSE-H2S-VEGF axis might participate in proangiogenesis effects of DH injection in diabetic hind limb ischemia model mice, suggesting a potential therapy for diabetic patients with critical limb ischemia.

Perinatal exposure to low-dose bisphenol A impairs spatial learning and memory in male rats.

Bisphenol A (BPA) is an estrogenic endocrine disruptor used for producing polycarbonate plastics and epoxy resins. This study investigated the effects of perinatal BPA exposure on learning and memory, general activity, and emotionality in male Sprague Dawley rats using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) used to assess spatial learning and memory. Mother rats were orally administered BPA (50 or 500 µg∙kg(-1)/day) or vehicle (1 ml∙kg(-1)/day) from gestational day 10 to postnatal day 14. In the MAZE test, compared to the offspring of vehicle-treated rat mothers, male offspring of mothers exposed to 50 µg∙kg(-1)/day of BPA, but not those of mothers exposed to 500 µg∙kg(-1)/day of BPA, needed significantly more time to reach the reward. Although male offspring of mothers exposed to 50 µg∙kg(-1)/day of BPA showed an increase in a behavioral measure of wariness after repeated testing in the open-field test, no significant effects were observed in locomotor activities. No significant differences were observed in any other behavioral test including the elevated plus-maze test. The present study suggests that perinatal exposure to low-dose BPA specifically and non-monotonically impairs spatial learning and memory in male offspring rats.