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Chronic excessive ethanol consumption damages the central nervous system and causes neurobehavioral changes, such as cognitive impairment, which is related to oxidative stress and inhibition of neurogenesis in the hippocampus. It is known that promoting neurogenesis improves learning memory, anxiety and depression. Lycium barbarum L. polyphenol (LBP) is the main active ingredient of Lycium barbarum L., which has excellent neuroprotective effects. However, the effects and mechanisms of LBP on ethanol-induced cognitive impairment are unclear.
To assess the effects and mechanisms of LBP on ethanol-induced cognitive impairment in mice.
Eight-weeks-old adult C57BL/6J mice were allowed to drink ethanol (10%) to establish a model of ethanol-induced cognitive impairment. From the 29th day of LBP (25, 50, 100, 200, 400mg/kg, intragastric administration), the locomotor activity, novel object recognition (NOR), Y maze and Morris water maze (MWM) were sequentially performed to investigate the effect of LBP on ethanairment in ethanol-induced mice, which is attributed to the promotion of hippocampal neurogenesis and reduction of oxidative stress.
LBP significantly improves cognitive impairment in ethanol-induced mice, which is attributed to the promotion of hippocampal neurogenesis and reduction of oxidative stress.
This study aims to evaluate the effectiveness and safety of oral Chinese herbal medicine (CHM) in the treatment of knee osteoarthritis (KOA).
Systematic review and meta-analysis of randomized controlled trials (RCTs).
A computer was used to retrieve all RCTs of CHM in the treatment of KOA from 7 databases (PubMed; Embase; Cochrane Central Register of Controlled Trials; China National Knowledge Infrastructure; Chinese VIP Information Database; Chinese Biomedical Database and Wanfang Med Database) from the establishment to August 2021. The literature was organized using NoteExpress, and literature screening and data extraction were conducted by two researchers independently by the inclusion and exclusion criteria. Quality evaluation was performed using GRADE, and the meta-analysis was performed using RevMan5.4.
A total of 31 RCTs and 3115 cases are included. The following meta-analysis results are observed (1) WOMAC CHM vs. placebo (SMD=-0.87, 95% CI -1.27 to -0.47, P < 0.0001), CHM vs. Western medicn of CHM + Western medicine is superior to Western medicine alone in the treatment of KOA. However, due to the existence of certain biases in the included studies, and the need for further study on the effective components of Chinese medicine, a positive conclusion on the efficacy of traditional CHM in the treatment of KOA cannot be drawn and needs to be confirmed by high-quality clinical RCTs.
Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease characterized by persistent inflammation and hyperplasia of the synovial membrane, the degradation of cartilage, and the erosion of bones in diarthrodial joints. The inflamed joints of patients with RA have been recognized to be a site of hypoxic microenvironment which results in an imbalance of lactate metabolism and the accumulation of lactate. Lactate is no longer considered solely a metabolic waste product of glycolysis, but also a combustion aid in the progression of RA from the early stages of inflammation to the late stages of bone destruction.
To review the pathogenic mechanisms of lactate metabolism in RA and investigate the potential of natural compounds for treating RA linked to the regulation of imbalance in lactate metabolism.
Research advances in our understanding of lactate metabolism in the pathogenesis of RA and novel pharmacological approaches of natural compounds by targeting lactate metabolic signaling were comprehensively reviewed and deeply discussed.
Lactate produced by RA synovial fibroblasts (RASFs) acts on targeted cells such as T cells, macrophages, dendritic cells and osteoclasts, and affects their differentiation, activation and function to accelerate the development of RA. Many natural compounds show therapeutic potential for RA by regulating glycolytic rate-limiting enzymes to limit lactate production, and affecting monocarboxylate transporter and acetyl-CoA carboxylase to inhibit lactate transport and conversion.
Regulation of imbalance in lactate metabolism offers novel therapeutic approaches for RA, and natural compounds capable of targeting lactate metabolic signaling constitute potential candidates for development of drugs RA.
Regulation of imbalance in lactate metabolism offers novel therapeutic approaches for RA, and natural compounds capable of targeting lactate metabolic signaling constitute potential candidates for development of drugs RA.
Asiatic acid (AA) is a naturally pentacyclic triterpenoids extracted from traditional medicine Centella asiatica l. that has demonstrated possesses potential health benefits and antitumor ability. However, the precise anticancer effects and mechanisms by which AA impact RCC cells remains unclear.
Cell proliferation and cell cycle distribution were detected by MTT, colony formation assay and PI stain by flow cytometry, respectively. Cell mobility and invasiveness were determined by in vitro migration and invasion assay. The secretory MMP15 was detected by ELISA assay. Quantitative RT-PCR, siRNA, and immunoblot were used to determine gene expression/regulation and protein expression, respectively. Antimetastatic effect of AA were performed to lung nodule numbers in vivo metastasis mice model. MMP15, pERK1/2 and p-p38MAPK expressions were determined by immunohistochemistry.
Our findings indicated cell proliferation and cell cycle distribution of RCC cells were not significantly influenced by AA treatment. AA suppressed cell migration, invasion and significantly down-regulated mRNA and protein expression of MMP-15 (Matrix Metallopeptidase-15). Activation of ERK1/2 and p38MAPK were inhibited with AA, whereas combined AA with siRNA-ERK or siRNA-p38MAPK markedly reduced the metastatic effect and decreased MMP-15 expression in 786-O and A498 cells. Finally, AA significantly reduced the lung metastasis formation and metastasis-related proteins of human 786-O cells in vivo metastasis mice model.
AA inhibits the metastatic properties of RCC cells via inhibition of the p-ERK/p-p38MAPK axis and the subsequent down-regulation of MMP-15 in vitro and in vivo. Further study of AA as a potential anti-metastatic agent for RCC is warranted.
AA inhibits the metastatic properties of RCC cells via inhibition of the p-ERK/p-p38MAPK axis and the subsequent down-regulation of MMP-15 in vitro and in vivo. Further study of AA as a potential anti-metastatic agent for RCC is warranted.
Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation.
ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR).
174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300m (p=0.012). No associations with outcome were observed with mDSP cutoff 200m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p=0.001), DLCO% (p=0.0001) and sPAP (p=0.031) on multivariate analysis. selleck inhibitor These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p=0.015).
Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.
Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.Park use is associated with health, yet our understanding of park features related to their use is limited. Singapore's parks were audited for 30 micro-features, then geospatial analysis characterized micro-features scores for parks nearest to participants' homes. Adults (3,435) reported their park use and park-based physical activity. Using linear regression models, we found living near a park with higher micro-features scores was associated with more time in parks and park-based physical activity. Specific micro-features were associated with more park time (wildlife areas, water features, forested areas, unpaved trails (2-2.6 h/month, p less then 0.05)) and with physical activity in parks (water features, forested areas, large playground, open green spaces (1.8-2.2 h/month, p less then 0.05)). These findings could inform parks planning to support population-health.In forensic applications, there is an increasing demand for the analysis of DNA profiles arising from missing person identification (MPI) cases. A specific DNA profile may originate from a single source or more than one contributor (i.e., a DNA mixture). When direct references are not available, indirect relative references can be used to identify missing persons by kinship analysis. As a novel kind of multiallelic marker, microhaplotypes have proven promising for relatedness determination and mixture deconvolution. Herein, we developed a large panel of 185 microhaplotype markers and demonstrated its application in different scenarios of relationship inference through a simulation study and real pedigree analysis, combined with probabilistic genotyping models for data interpretation. Based on single-source profiles, it was shown that the present microhaplotype panel was sufficient for pairwise close relative testing (parent/child, full-sibling and 2nd-degree relative). For more distant relatives (3rd-degree r. Furthermore, this study could be extended to more complex scenarios, such as determining the relatedness of contributors in (or among) mixed DNA profiles, if combined with different statistical frameworks.Unexpected cardiac deaths are a current challenge to healthcare systems. In adults, coronary artery disease and acquired cardiomyopathies are the most frequent causes of sudden cardiac death while in younger than 35 years old, the main cause is represented by non-ischemic diseases, usually inherited. Nowadays, around 10%-15% of unexpected deaths remain without a definite cause of decease after a complete autopsy, then classified as deaths potentially due to an inherited arrhythmia. Discrete abnormalities in some of the heart measures have been considered as potential predictors or risk factors for sudden cardiac death. However, role of non-benign genetic variants in these scattered heart alterations remains to be clarified, especially if variants are classified of ambiguous role. Clinicians usually only take into consideration pathogenic variants for decision-making. It is yet unclear what the role of VUS genetic variants in modifying the anatomical parameters of the heart. We hypothesize that some heart measures might be influenced by polygenic components as some variants may individually confer minor risk but may actually produce additive effects when combined with others.
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