Strouddesai0229

MPTP models have been developed to mimic human Parkinson's disease and serve as an indispensable tool for studying PD. Among them, subacute MPTP PD models are popular due to their short modeling period and similarity to PD pathology. However, the early pathophysiological mechanism of the model remains to be further clarified. More and more studies have shown that dysregulation of miRNAs plays an important role in the occurrence and development of neurodegenerative diseases, including PD. In this study, we identified 43 differentially expressed microRNAs (miRNAs) in the ventral midbrain of MPTP-induced subacute PD mouse by RNA sequencing. Further bioinformatics analysis revealed that these miRNAs were significantly enriched in axon guidance/neuron projection, metabolic pathways/cellular macromolecule metabolic process and PI3K/AKT signaling pathways, which were involved in the occurrence and development of early PD. Thus, targeted regulation of these miRNAs may reverse the neurodegeneration of early PD.Losartan, an angiotensin II type 1 receptor blocker, exerts protective effect on soleus muscle atrophy in female rats. Thus, we aimed to examine the effect of losartan treatment on the recovery of atrophied soleus muscles. Female Wistar rats were subjected to hindlimb unloading for 7 d and then reloading for 7 d with either phosphate-buffered saline (PBS; n = 9) or losartan (40 mg/kg/day; n = 9). The soleus muscles were removed at rest (sedentary control [SED]; n = 9), after 7 d of hindlimb unloading (HU; n = 9), and after 7 d of reloading (HUR-PBS or HUR-LOS; n = 9 each). The absolute and relative weights, and fiber cross-sectional area (CSA) of the soleus muscles of rats in the HU group were significantly reduced as compared to those of the rats in the SED group at 7 d post-hindlimb unloading. Seven days of reloading significantly increased the muscle weights of rats in the HUR-PBS and HUR-LOS groups, with the recovery rate of the absolute muscle weight and type I fiber CSA being significantly higher in the HUR-LOS group (6.1% and 10.1%, respectively) than in the HUR-PBS group (4.7% and 5.2%, respectively) (p less then 0.05). Moreover, the absolute and relative muscle weight in HUR-PBS were lower than SED; however, no significant difference was observed between the SED and HUR-LOS groups. CSAs of type I and IIa fiber were significantly higher in the HUR-LOS group than in the HU group. Losartan administration during reloading resulted in increased Smad1/5/8 and mTOR signaling and decreased Smad2/3 signaling and protein ubiquitination, facilitating the recovery of atrophied soleus muscle. Therefore, losartan administration-induced muscle recovery may partially be attributed to enhanced Smad1/5/8 and mTOR signaling activation, and reduced activation of canonical TGF-β signaling (Smad2/3) in the soleus muscle.Myocardial infarction (MI) is one of the top causes of morbidity and mortality in the world. Prevention/treatment of MI is of utmost importance. This study planned to appraise the molecular mechanisms of β-caryophyllene on the intrinsic pathway of cardiomyocyte apoptosis in isoproterenol-induced myocardial infarcted rats. Rats were induced MI by isoproterenol (100 mg/kg body weight). The serum cardiac diagnostic markers, heart lipid hydroperoxides, heart lysosomal thiobarbituric acid reactive substances, and serum/heart lysosomal enzymes were considerably (P less then 0.05) augmented, while heart antioxidants, heart lysosomal β-glucuronidase and cathepsin-D were considerably (P less then 0.05) lessened in isoproterenol-induced myocardial infarcted rats. Cytosporone B mouse A reverse transcription-polymerase chain reaction study revealed altered expressions of B-cell lymphoma gene-2, B-cell lymphoma - extra-large, B-cell lymphoma-2 associated-x, and B-cell lymphoma-2 associated death promoter genes. Further, transmission electron microscopic study depicted damaged heart lysosomal structure. Histological study revealed mononuclear cell infiltration and congested dilated blood capillaries in between affected cardiac muscle fibres. Further, 2,3,5-triphenyl tetrazolium chloride staining showed a larger myocardial infarct size. The β-caryophyllene (20 mg/kg body weight) pre-and co-treatment orally, daily, for 21 days considerably (P less then 0.05) ameliorated all these altered biochemical, transmission electron microscopic, molecular and histological parameters evaluated in myocardial infarcted rats. Thus, β-caryophyllene inhibited oxidative stress and lysosomal leakage, preserved the heart, and heart lysosomal structure, and prevented the intrinsic pathway of apoptosis. Moreover, it reduced infarct size. The antioxidant effects of β-caryophyllene are the possible mechanism for the observed anti-oxidative stress, anti-lysosomal damage, anti-apoptotic, and myocardial infarct size limiting effects.Deregulation of protein post-translational modifications is intensively involved in the etiology of diseases, including degenerative diseases, inflammatory injuries, and cancers. Acetylation is one of the most common post-translational modifications of proteins, and the acetylation levels are controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs). HATs loosen the chromatin structure by neutralizing the positive charge of lysine residues of histones; whereas HDACs deacetylate certain histones, thus inhibiting gene transcription. Compared with HATs, HDACs have been more intensively studied, particularly regarding their clinical significance. HDACs extensively participate in the regulation of proliferation, migration, angiogenesis, immune escape, and therapeutic resistance of cancer cells, thus emerging as critical targets for clinical cancer therapy. Compared to HATs, inhibitors of HDAC have been clinically used for cancer treatment. Here, we enumerate and integratethe mechanisms of HDAC family members in tumorigenesis and cancer progression, and address the new and exciting therapeutic implications of single or combined HDAC inhibitor (HDACi) treatment.To screen potent terpenoid compounds against allergic inflammation in vitro and in vivo, five terpenoid compounds including menthone, farnesol, oridonin, β-escin and lupeol, were first selected to compare their anti-allergic inflammation potential using mouse lung mast cells in vitro. Among five selected terpenoid compounds, just menthone treatment decreased TNF-α/IL-10 secretion ratios in lipopolysaccharide -stimulated mast cells in vitro. As a result, menthone was further chosen to treat ovalbumin (OVA)-sensitized and challenged BALB/c mice by gavage for 5 weeks. There were six groups including dietary control (DC group, 0 mg menthone/kg b.w./day), 8 (ML group), 40 (MM group) as well as 200 mg menthone/kg b.w./day (MH group) by gavage, positive control (PC group, 3 mg dexamethasone/kg b.w. by gavage before OVA challenge) and non-treatment control (NTC group, normal mice without treatment) in the experiment. Changes of inflammatory mediators, cell distribution, Th1/Th2 and pro-/anti-inflammatory cytokines secretion as well as relative gene expression amounts of six receptors related to allergic inflammation in the lungs and airways were measured. The results showed that middle menthone supplementation (40 mg menthone/kg b.w./day) in vivo decreased protein and eotaxin, but increased Th1 cytokine levels in the bronchoalveolar lavage fluid. Menthone supplementation inhibited eosinophilia, mast cell degranulation, chemokine (C-C motif) receptor 3 (CC receptor 3) and chemokine (C-X-C motif) receptor 1 (CXC receptor 1) gene expression amounts in the lungs, but restored the percentage of monocytes/macrophages. Our results suggest that menthone supplementation may alleviate allergic asthma through regulating airway allergic inflammation, protein overproduction, eosinophils infiltration, Th1/Th2 immune balance, CC receptor 3 and CXC receptor 1 gene expression amounts in the lungs but restoring the percentage of monocytes/macrophages in allergic asthmatic mice.Astrocytes are the main support cells of the central nervous system. They also participate in neuroimmune reactions. In response to pathological and immune stimuli, astrocytes transform to reactive states characterized by increased release of inflammatory mediators. Some of these molecules are neuroprotective and inflammation resolving while others, including reactive oxygen species (ROS), nitric oxide (NO), matrix metalloproteinase (MMP)- 9, L-glutamate, and tumor necrosis factor α (TNF), are well-established toxins known to cause damage to surrounding cells and tissues. We hypothesized that similar to microglia, the brain immune cells, reactive astrocytes can release a broader set of diverse molecules that are potentially neurotoxic. A literature search was conducted to identify such molecules using the following two criteria 1) evidence of their expression and secretion by astrocytes and 2) direct neurotoxic action. This review describes 14 structurally diverse molecules as less-established astrocyte neurove understanding of the full spectrum of neurotoxins released by reactive astrocytes is key to understanding neuroinflammatory diseases characterized by the adverse activation of these cells and may guide the development of novel treatment strategies.How fetal brain development is regulated at the molecular level is not well understood. Due to ethical challenges associated with research on the human fetus, large animals particularly pigs are increasingly used to study development and disorders of fetal brain. The pig fetal brain grows rapidly during the last ∼ 50 days before birth which is around day 60 (d60) of pig gestation. But what regulates the onset of accelerated growth of the brain is unknown. The current study tests the hypothesis that epigenetic alteration around d60 is involved in the onset of rapid growth of fetal brain of pig. To test this hypothesis, DNA methylation changes of fetal brain was assessed in a genome-wide manner by Enzymatic Methyl-seq (EM-seq) during two gestational periods (GP) d45 vs. d60 (GP1) and d60 vs. d90 (GP2). The cytosine-guanine (CpG) methylation data was analyzed in an integrative manner with the RNA-seq data generated from the same brain samples from our earlier study. A neural network based modeling approach was implemented to learn changes in methylation patterns of the differentially expressed genes, and then predict methylations of the brain in a genome-wide manner during rapid growth. This approach identified specific methylations that changed in a mutually informative manner during rapid growth of the fetal brain. These methylations were significantly overrepresented in specific genic as well as intergenic features including CpG islands, introns, and untranslated regions. In addition, sex-bias methylations of known single nucleotide polymorphic sites were also identified in the fetal brain ide during rapid growth.

To date, few studies have focused on examining either the direct or indirect effect of physical frailty on cognitive impairment. This study aimed to investigate the moderating effects of social relationships, including their individual components in the role of depressive symptoms as a mediator between frailty and cognitive impairment.

This study included a total of 7525 Chinese older adults from the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Mediation analyses and moderated mediation effect analysis fully adjusted for all potential confounding factors were conducted.

Significant correlations were found between frailty, depression, social relationships, and cognitive function. Depression partially mediated the association of frailty with cognitive function [B=-0.198; 95% confidence interval (CI) (-0.258, -0.143)]. Social relationships moderated the effect of frailty on cognitive function through both path b (depression-cognitive function) [B=0.137; 95% CI (0.045, 0.230)], and path c' (frailty-cognitive function) [B=0.