Kjeldgaardellison4761
Additionally, the expression level of LC3 and the ratio of LC3II/LC3I were increased, but the expression level of p62 was suppressed by compound 2 whereas an autophagy inhibitor 3-methyladenine (3-MA) significantly abolished the inhibitory effects of compound 2 on the generation of ROS and the protein expression of NLRP3 inflammasome. Moreover, compound 2 could ameliorate the expression ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Interestingly, mTOR activator MHY-1485 could block the promotion effect of compound 2 on autophagy regulation and inhibitory effect of compound 2 on induction of ROS and IL-1β. In conclusion, these findings suggested that compound 2 may effectively improve NLRP3 inflammasome-mediated gout via PI3K-AKT-mTOR-dependent autophagy and could be further investigated as a potential agent against gout.The incidence of liver diseases, such as nonalcoholic fatty liver disease and drug-induced liver injury, continues to rise and is one of the leading causes of acute hepatitis. Current trends suggest that these types of conditions will increase in the coming years. There are few drugs available for the prevention or treatment of hepatic diseases, and there is a growing need for the development of safe hepatoprotective agents. The medicinal plant, Turnera diffusa, has many ethnopharmacological uses, one of which is the production of a flavonoid named hepatodamianol, which is the principal component responsible for this plant's hepatoprotective properties. In the present study, we describe the development and standardization of an active extract obtained from T. diffusa. We conducted nuclear magnetic resonance spectroscopy to identify hepatodamianol unambiguously in each sample. Using this extract, hepatoprotection could be demonstrated in vivo for the first time. The hepatoprotective effect did not display a significant difference in vivo when compared with silymarin used as a positive control at the same doses. Implementation of quality criteria used for standardization, such as flavonoid and hepatodamianol content, hepatoprotective activity, and absence of residual solvents, will allow future preclinical trials with this herbal drug.
Acupuncture is a commonly used complementary treatment for flaccid hemiplegia caused by stroke, but evidences from previous randomized trials were inconclusive. The purpose of this study was to evaluate the efficacy and safety of acupuncture in a comprehensive synthesis.
We searched literature from eight databases from their inception to December 2020. We included randomized controlled trials of acupuncture for the treatment of flaccid hemiplegia following stroke. The meta-analysis was carried out using Review Manager 5.3 and Stata 16.0. The main indicator was the Fugl-Meyer Assessment scale. The modified Barthel Index scale, Quality Of Life Assessment scale, Mini-Mental State Examination scale, Berg Balance Scale, Neurological Deficit Assessment scale, and the treatment effective rate were used to measure the secondary indicators. Adverse events from individual studies were used to determine safety.
Our search returned 7624 records, of which 27 studies involving a total of 1,293 patients fulfilled our inclusion criteria. To be noted, our results indicated that significant improvements in the scores of the primary indicator showed better clinical scores among the three groups with acupuncture than without acupuncture acupuncture compared with rehabilitation, 13.53 (95% CI 11.65-14.41,
< 0.01); acupuncture plus rehabilitation compared with rehabilitation, 9.84 (95% CI 6.45-13.24,
< 0.01,
= 98%); and acupuncture plus Western medicine therapy compared with Western medicine, 16.86 (95% CI 15.89-17.84,
< 0.01,
= 38%), and the secondary indicators showed the same tendency.
Acupuncture was effective and safe in the patients with flaccid hemiplegia after stroke, although there was high heterogeneity between studies.
Acupuncture was effective and safe in the patients with flaccid hemiplegia after stroke, although there was high heterogeneity between studies.
By integrating meta-analysis and network pharmacology strategy, the clinical efficacy of Zhishe Tongluo capsule in the treatment of cerebral infarction was evaluated, and the intervention mechanism was preliminary explored.
Through meta-analysis, the Chinese and English literature of the randomized controlled trial (RCT) of Zhishe Tongluo capsule in the treatment of cerebral infarction was comprehensively searched. Based on the standard of Na Pai, the quantitative literature was determined and the Review Manager data were statistically analyzed.
A total of 10 RCTs literatures were included. These literatures included a total of 1278 subjects, of which 670 were in the treatment group and 608 were in the control group. In terms of indicators of efficiency and adverse reaction rate, the treatment group was better than the control group. There was a statistical difference (
< 0.05); a total of 559 chemical constituents and 2306 potential targets were obtained from the online database. Of these, 201 comeology, but the overall evidence level is low, which still needs to be further supported by large-scale and multicenter RCTs; intervention of brain infarction by Zhishe Tongluo capsule is a comprehensive result of multicomponent and multi-target interactions. On the basis of the combined meta-analysis and network pharmacology in scientific attempts, it also provides a reference for the clinical evaluation of other drugs and mechanism research.
Elevated uric acid (UA) has been found to damage pancreatic
-cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). Astragaloside IV (AS-IV), a major active monomer extracted from
(Fisch.) Bunge. which belongs to TRIB. Galegeae (Br.) Torrey et Gray,
, exhibits various activities in a pathophysiological environment and has been widely employed to treat diseases. However, the effects of AS-IV on UA-induced pancreatic
-cell damage need to be investigated and the associating mechanism needs to be elucidated. This study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic
-cell dysfunction in T2D.
UA-treated Min6 cells were exposed to AS-IV or wortmannin. Thereafter, the 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and flow cytometry were employed to determine the effect of AS-IV on cell proliferation and apoptosis, respectively. Insulin secretion was evaluated using the glucose-stimulaom UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.
Collectively, our data suggest that AS-IV protected pancreatic β-cells from UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.Dysfunctions in adipose tissue cells are responsible for several obesity-related metabolic diseases. Understanding the process of adipocyte formation is thus fundamental for understanding these diseases. The adipocyte differentiation of adipose-derived stem/stromal cells (ADSCs) showed a reduction in the mRNA level of the interleukin 21 receptor (IL21R) during this process. Although the receptor has been associated with metabolic diseases, few studies have examined its function in stem cells. In this study, we used confocal immunofluorescence assays to determine that IL21R colocalizes with mitochondrial protein ATP5B, ALDH4A1, and the nucleus of human ADSCs. We demonstrated that silencing and overexpression of IL21R did not affect the cell proliferation and mitochondrial activity of ADSCs. However, IL21R silencing did reduce ADSC adipogenic capacity. Further studies are needed to understand the mechanism involved between IL21R and the adipogenic differentiation process.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, and its incidence is obviously increasing. The NT5DC family has been shown to be involved in the progression of many tumors. However, the biological function of NT5DC family members in HCC is still not well understood.
Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, cBioPortal, GeneMANIA, Metascape, and TIMER were applied to assess the biological function of NT5DC family members in HCC.
Most of the NT5DC family members were highly expressed in HCC. High expression of NT5C2, NT5DC2, and NT5DC3 was closely associated with higher tumor stage and poor overall survival (OS). In addition, high NT5DC2 and NT5DC3 expression also predicted poor disease-free survival (DFS). Enrichment analysis revealed that the NT5DC family in HCC mainly involved the IMP metabolic process, purine ribonucleoside monophosphate metabolic process, and purine nucleoside monophosphate metabolic process. The expression of NT5DC family members was closely related to the infiltration of some immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells.
Our findings provided new insights into the biological function and prognostic value of NT5DC family members in HCC.
Our findings provided new insights into the biological function and prognostic value of NT5DC family members in HCC.
Type 2 diabetes (T2D) as a worldwide chronic disease combined with the COVID-19 pandemic prompts the need for improving the management of hospitalized COVID-19 patients with preexisting T2D to reduce complications and the risk of death. This study aimed to identify clinical factors associated with COVID-19 outcomes specifically targeted at T2D patients and build an individualized risk prediction nomogram for risk stratification and early clinical intervention to reduce mortality.
In this retrospective study, the clinical characteristics of 382 confirmed COVID-19 patients, consisting of 108 with and 274 without preexisting T2D, from January 8 to March 7, 2020, in Tianyou Hospital in Wuhan, China, were collected and analyzed. Univariate and multivariate Cox regression models were performed to identify specific clinical factors associated with mortality of COVID-19 patients with T2D. An individualized risk prediction nomogram was developed and evaluated by discrimination and calibration.
Nearly 15% (16/108incorporating specific prognostic factors, this study provided a user-friendly graphical risk prediction tool for clinicians to quickly identify high-risk T2D patients hospitalized for COVID-19.Bladder pain syndrome (BPS) is a prevalent and pervasive disease. The physical and psychological sequelae can be very burdensome for the patient, and the condition represents a real challenge for the clinician as well. With no simple pathognomonic test, finding harmony in navigating patient care can be demanding. Diagnosis and management rely upon a multidisciplinary and holistic approach. Treatment options include conservative measures and pharmacotherapies as well as bladder instillation therapies. Ultimately, surgery may be offered but only in cases of refractory disease. This article offers a pragmatic guide for clinicians managing this challenging disease.
