Lindethestrup3739
Parkinson's disease (PD) is a common central nervous system degenerative disease in middle-aged and elderly people. Our study aimed to illuminate the relationship and mechanism of long-chain non-coding RNA SNHG1 and miRNA (miR)-216a-3p in PD.
Human neuroblastoma cell lines were treated with MPP
to construct a PD model. Real-time fluorescent quantitative PCR was used to detect the cellular expression of SNHG1. Neuronal cell activity and apoptosis were compared before and after SNHG1 knock-down, as was neuronal miR-216a-3p expression. Further, a luciferase reporter gene experiment was performed to verify BAX as the target of miR-216a-3p. Anti-miR-216a-3p and BAX were co-transfected into PD model cells, and neuronal cellular activity and apoptosis were observed. Finally, the potential regulatory network of SNHG1/miR-216a-3p/BAX in PD was investigated.
The expression of miR-216a-3p was decreased in the PD model cells, and re-expression reversed the high apoptotic rate and cell vitality inhibition in PD model cells. SNHG1 interacted with miR-216a-3p and negatively regulated its upstream molecules, while miR-216a-3p attenuated the effect of SNHG1 knock-down on neurons. The overexpression of BAX in the PD cell model blocked the damage by miR-216a-3p to neurons. At the same time, SNHG1 acted as a coordinator, mediating the regulation of BAX via miR-216a-3p, thereby affecting the activity and apoptotic rate of neurons in the PD model.
SNHG1 interacts with miR-216a-3p to regulate the expression of BAX. This SNHG1/miR-216a-3p/BAX molecular regulatory network is implicated in the pathogenesis of PD.
SNHG1 interacts with miR-216a-3p to regulate the expression of BAX. This SNHG1/miR-216a-3p/BAX molecular regulatory network is implicated in the pathogenesis of PD.
Peritonitis is a common complication in which the peritoneum becomes inflamed. Peroxisome proliferator-activated receptor (PPAR)γ agonists and extracellular signal-regulated kinases 1/2 (ERK1/2) inactivation have been found to restore damage caused by lipopolysaccharide-induced (LPS) inflammation. This study aimed to investigate the association between PPARγ and ERK1/2 in LPS-induced inflammation in peritonitis.
Human peritoneal mesothelial cells were maintained in Dulbecco's Modified Eagle Medium and treated with LPS under a series of different concentrations and treatment times. Cellular interleukins-1βeta (IL-1β), cellular interleukins-6 (IL-6), cellular interleukins-12 (IL-12) were measured by enzyme-linked immunosorbent assay (ELISA) assay. Expression or activation of cyclin-dependent kinase (CDK)5, ERK1/2, and PPARγ was detected using quantitative real-time PCR and/or western blot.
LPS induced dose- and time-dependent increments in the cellular IL-1β, IL-6, and IL-12 contents, cyclin-dependent kinase 5 (CDK5) expression, and PPARγ
phosphorylation. Treatment with 1 µg/mL LPS for 12 hours was the optimal experimental design for inflammation stimulation. The concentration of LPS over 1 µg/mL or treatment more than 12 hours reduced the inflammatory status. LPS stimulation also activated ERK1/2 and increased its interaction with CDK5. Further, ERK1/2 inhibition by AZD0364 prevented IL-1β, IL-6, IL-12, and CDK5 expression, as well as activation of ERK1/2 and phosphorylation of PPARγ, induced by LPS. Knockdown of CDK5 using its siRNA caused similar changes as AZD0364, minus ERK1/2 inactivation.
Our results suggested that LPS-induced inflammation in human peritoneal mesothelial cells can be partly suppressed by inhibiting the ERK1/2/CDK5/PPARγ axis.
Our results suggested that LPS-induced inflammation in human peritoneal mesothelial cells can be partly suppressed by inhibiting the ERK1/2/CDK5/PPARγ axis.
Extranodal natural killer/T-cell lymphoma (NKTCL), nasal type mostly involves the upper aerodigestive tract (UAT). NKTCLs derived from the UAT are referred to as nasal NKTCLs, while those without UAT involvement are referred to as extra-nasal NKTCLs. In this study, we aimed to investigate the outcomes and survival trends of NKTCLs from different anatomical sites.
Data from the US Surveillance, Epidemiology, and End Results (SEER) database on NKTCL (diagnosed between 1987 and 2016) were retrospectively analyzed.
A total of 714 patients with NKTCL were included. The median overall survival (OS) and cancer-specific survival (CSS) were 36 and 57 months, respectively. For the entire cohort, the OS was improved from era 1 to era 2 with marginal significance (P=0.0595), however, no improvement was shown in CSS. For nasal NKTCLs, the OS of patients from era 2 was significantly improved compared to that of patients from era 1 (P=0.0244). The OS was significantly improved in non-cavity nasal NKTCLs (P=0.031) but timal treatments for patients with NKTCLs.
The aim of this study was to investigate the effects of artesunate (ART) on breast epithelial cell proliferation
and
.
Immortalized human non-cancer mammary epithelial (MCF-10A) cells were used to determine the effect of ART on estrogen-induced mammary hyperplasia cells. We investigated the effect of ART on the synthesis of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) in MCF-10A by treating MCF-10A 36 h with different concentrations of ART (0, 100, 200, 400 µm, n=12/group). We then investigated the effect of ART on estrogen induced COX-2, PCNA, nuclear factor-kappa B (NF-κB), and pNF-κB synthesis by treating MCF-10A with both estrogen and ART (0, 50, 100, 200 µm, n=12/group). A mammary hyperplasia model (MGH) was established in rats. All rats (n=12) were divided into 4 groups [group A negative control (NC) + Art -; group B NC + Art +; group C MGH + Art -; group D MGH + Art +] by the random number table method and the effects of ART on estradiol-induced mammary hyperplasia, fibrosis, and phosphorylation of AKT and NF-κB were studied by histopathological staining, Masson trichrome staining, immunohistochemistry (IHC), and western blotting.
The proliferation and inflammation of mammary epithelial cells were blocked by ART (P<0.05). The phosphorylation of NF-κB induced by estradiol in MCF-10A was attenuated by ART (P<0.05). In the rat MGH, ART reduced cell proliferation and fibrosis (P<0.05) and inhibited the phosphorylation of AKT and NF-κB (P<0.05).
The drug ART inhibits estrogen-induced breast hyperplasia by blocking AKT and NFkB phosphorylation.
The drug ART inhibits estrogen-induced breast hyperplasia by blocking AKT and NFkB phosphorylation.
This study compared the efficacy and tolerability of available direct-acting antiviral (DAA) regimens between individuals aged 60 years and older and younger patients in a real-life setting. Specifically, we aimed to provide evidence of the efficacy and safety of DAAs in the treatment of older adults in Tianjin, China.
In this retrospective observational cohort study, patients with chronic hepatitis C virus (HCV) were enrolled between April 2018 and December 2019 at 2 tertiary hospitals in Tianjin, China. XST-14 order We assessed the sustained virologic response (SVR) 12 weeks (SVR12) after DAA treatment, and adverse events in two groups using age stratification by comparing older adults (≥60 years) and younger adults (<60 years). Logistic regression analyses were performed to explore the risk factors associated with the SVR12.
Of 1,106 patients, 440 (39.8%) were ≥60 years of age. The overall SVR12 rate was 97.8% in the entire cohort. In the older adult group, the SVR12 rate was 98.0% (431/440) compared to 97.7% n all age subgroups. Our observations suggest that DAA treatment should not be withheld even from older patients suffering from chronic HCV.
Valproic acid (VPA) is a common antiepileptic drug used to treat both generalized and partial epilepsy. Although there is increasing evidence to suggest that
gene polymorphisms are associated with interindividual variability of VPA metabolism, the results are debatable. Therefore, in the present study, we conducted a meta-analysis to evaluate the correlation between
gene polymorphisms and adjusted plasma VPA concentration.
The EMBASE, MEDLINE, and Cochrane Library databases were searched to obtain relevant studies. Eligible articles were reviewed, and data extraction was performed. We calculated 95% confidence intervals (CIs) and mean differences (MDs) to assess the strength of the relationship of
gene polymorphisms with adjusted plasma VPA concentration.
The meta-analysis included 6 studies involving 847 patients with epilepsy. The pooled analysis showed that the
A1075C (AA
AC) polymorphism was related to the adjusted plasma concentration of VPA (P=0.02, I
= 82%). Additionally, the AC p.
Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on the interaction between WZC and MTX is limited. This study aimed to investigate the effects of WZC on the pharmacokinetics of MTX in rats and to explore the role of membrane transport proteins OAT1/3 and P-gp in the interaction of these drugs.
Plasma MTX concentration was detected by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), and the messenger RNA (mRNA) and protein expression of OAT1/3 and P-gp was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses, respectively.
The study results revealed that co-administration of WZC decreased the CL
and V
of MTX, increased the C
and area under the curve [(AUC)
] of MTX, and inhibited OAT1/3 expression in the kidney and P-gp expression in the small intestine.
The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination.
The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination.
Spinal cord injury (SCI) is a life-changing event with an extremely poor prognosis. In our preliminary studies, electroacupuncture (EA) was found to promote the repair of SCI, which was closely related to the Notch signaling pathway. Therefore, in the present study, we hypothesized that EA protects against SCI by inhibiting the Notch signaling pathway and sought to investigate the underlying molecular mechanisms.
Rat and cell models of SCI were established. The expression of long non-coding RNA H19 was measured by real-time quantitative polymerase chain reaction. The expression levels of EZH2, Notch1, Notch3, Notch4, Hes1, and PS1 protein were measured by western blot. Cell apoptosis and viability were analyzed using flow cytometry and Cell Counting Kit-8 assays, respectively. The expressions of glial fibrillary acidic protein (GFAP) and nestin were detected by immunofluorescence staining.
The expressions of H19, EZH2, and GFAP were significantly increased after SCI but were inhibited by EA; in contrast, nestin expression was significantly decreased by SCI but was restored by EA.
