Association of four GSTs gene polymorphisms with Parkinson disease: A meta-analysis

Parkinson disease (PD) is a neurological disorder with huge destruction to human body, which affects approximately 2% of the population aged 65 years or older. As antioxidants in the stress defence systems, glutathione S-transferases (GSTs) are dimeric cytosolic enzymes with an important role in the pathogenesis of PD. The aim of this study was to evaluate the association between the polymorphisms of GST genes and PD. Meta-analyses were conducted from 17 studies (38 stages) among 3419 cases and 5686 controls between four polymorphisms (GSTT1 deletion polymorphism;GSTM1 deletion polymorphism;GSTP1-104: rs1695;GSTP1-114: rs1799811) and PD. There is no significant association between the four GST gene variants and PD. A further subgroup study by ethnicity observed a risky role of GSTM1 deletion polymorphism with PD in Europeans (p = 0.013, OR = 1.126, 95% CI = 1.025-1.236), and a protective role of GSTM1 deletion polymorphism with PD in Latin Americans (p = 0.032, OR = 0.750, 95% CI = 0.577-0.975). Our meta-analysis suggested that GSTM1 deletion polymorphism increased the risk of PD in Europeans, but reduced the risk of PD in Latin Americans. Future large-scale studies might be needed to confirm the ethnic difference of GSTM1 deletion polymorphism, and to check whether there was significant association of PD for other GST genetic polymorphisms.

A comprehensive meta-analysis of the association between three <i>IL</i>1B polymorphisms and rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory disease that causes huge destruction to human body. IL1B encodes key mediator IL-1β protein, which plays an important role in the pathogenesis of inflammatory syndromes. The aim of this study was to evaluate the association between IL1B polymorphisms and RA. A meta-analysis was performed on the association between three IL1B polymorphisms (IL1B-31: rs1143627;IL1B-511: rs16944;IL1B + 3954: rs1143634) and RA. A trend of significant association was observed between IL1B + 3954 and RA (p = 0.06, odd ratio (OR) = 1.19, 95% confidential interval (CI) = 1.00-1.42). A significant association was found in Europeans under the dominant model between IL1B-511T and RA (p = 0.03, OR = 0.89, 95% CI = 0.81-0.99). Our meta-analysis indicated that IL1B ? 511-T played a protective role against RA in Europeans, and that IL1B + 3954-T had the potential to increase the risk of RA. Future large-scale studies should be considered to confirm the association between IL1B polymorphisms and RA.

Meta-analyses of nine polymorphisms of six genes with the risk of schizophrenia

The aim of this study was to determine whether 9 genetic polymorphisms confered susceptibility to schizophrenia (SCZ). The authors conducted meta-analyses on associations between SCZ and 9 variants of 6 genes including PIK3C3 (432C > T), ABCB1 (C3435T and G2677T), CTLA4 (+49A/G), OLIG2 (rs762178), GAD1 (rs1978340, rs3749034 and rs769395), and GRIN1 (G1001C). A total of 34 case-control studies were involved in our meta-analyses. Our results showed no significant association between all the loci and SCZ. This meta-analysis confirmed a lack of association of SCZ for 9 genetic polymorphisms including GRIN1 G1001C, ABCB1 C3435T and G2677T, CTLA4 + 49A/G, OLIG2 rs762178, GAD1 gene rs1978340, rs3749034 and rs769395, and PIK3C3 432C > T.

Non-coding RNAs and gastric cancer

Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.

VEGFR2 inhibition hampers breast cancer cell proliferation via enhanced mitochondrial biogenesis

Objective:Vascular endothelial growth factor(VEGF),apart from its predominant roles in angiogenesis,can enhance cancer cell proliferation,but its mechanisms remain elusive.The purpose of the present study was therefore to identify how VEGF regulates cancer cell proliferation.Methods:VEGF effects on cancer cell proliferation were investigated with the VEGF receptor 2 inhibitor,Ki8751,and the breast cancer cell lines,MCF-7 and MDA-MB-231,using flow cytometry,mass spectrometry,immunoblotting,and confocal microscopy.Data were analyzed using one-way analysis of variance followed by Tukey’s multiple comparison test.Results:VEGF blockade by Ki8751 significantly reduced cancer cell proliferation,and enhanced breast cancer cell apoptosis.Mass spectrometric analyses revealed that Ki8751 treatment significantly upregulated the expression of mitochondrial proteins,suggesting the involvement of mitochondrial biogenesis.Confocal microscopy and flow cytometric analyses showed that Ki8751 treatment robustly increased the mitochondrial masses of both cancer cells,induced endomitosis,and arrested cancer cells in the high aneuploid phase.VEGFR2 knockdown by sh RNAs showed similar effects to those of Ki8751,confirming the specificity of Ki8751 treatment.Enhanced mitochondrial biogenesis increased mitochondrial oxidative phosphorylation and stimulated reactive oxygen species(ROS)production,which induced cancer cell apoptosis.Furthermore,Ki8751 treatment downregulated the phosphorylation of Akt and PGC1α,and translocated PGC1αinto the nucleus.The PGC1αalterations increased mitochondrial transcription factor A(TFAM)expression and subsequently increased mitochondrial biogenesis.Conclusions:VEGF enhances cancer cell proliferation by decreasing Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis,ROS production,and cell apoptosis.These findings suggested the anticancer potential of Ki8751 via increased mitochondrial biogenesis and ROS production.

中药的抗炎作用及分子机制

Traditional Chinese medicines(TCMs)are great treasures in pharmacological history with records of more than 3000 years.From ancient times to the present,TCMs of clearing heat,eliminating dampness,unblocking collaterals and removing toxins have been used in clinic to treat many infectious diseases and noninfectious chronic diseases,whose pathogenesis may involve inflammation induced by different causes.

Indirubin-30 -monoxime-loaded PLGA-PEG nanoparticles for potential Alzheimer's disease treatment

Alzheimer's disease(AD)is an irreversible neurodegenerative disorder,which is pathologically characterized by the deposits of β-amyloid(Aβ),and plays an important role in neuronal death.Indirubin-30-monoxime(I3M)showed neuroprotective effects against Aβ-induced neuronal apoptosis.However,the use of I3M in AD treatment is limited due to its low bioavailability.Herein,PLGA-PEG nanoparticles were synthesized for I3M loading.I3M could release sustainedly sustain release from the I3M-loaded PLGA-PEG nanoparticles(PLGA-PEG-I3M NPs)without obvious burst release.What's more,the PLGA-PEG-I3M NPs could significantly promote the uptake of I3M by PC12 cells through nanoparticle-mediated transport,and improve the efficacy of I3M on the inhibition of Aβfibrillization and oligomerization as well as the neuroprotective activity of I3M on Aβoligomers-induced neuronal death.Thus,the PLGA-PEG-I3M NPs may be a promising platform for AD therapy.