Zhoubarbee9657

Acute respiratory distress syndrome (ARDS) is one of the most fatal diseases worldwide. Pulmonary fibrosis occurs early in ARDS, and its severity plays a crucial role in ARDS mortality rate. Some studies suggested that fibroproliferation is an essential mechanism in ARDS. Mitofusion2 (Mfn2) overexpression plays a role in inhibiting cell proliferation. find more However, the role and potential mechanism of Mfn2 on the proliferation of fibroblasts is still unknown. In this study, we aimed at exploring the effect of Mfn2 on the human embryonic lung fibroblasts (HELF) and discussed its related mechanism. The HELF were treated with the Mfn2 overexpressing lentivirus (adv-Mfn2). The cell cycle was detected by flow cytometry. MTT, PCR and Western blotting were used to investigate the effect of Mfn2 on the proliferation of the HELF, collagen expression, the RAS-RAF-1-ERK1/2 pathway and the expression of cycle-related proteins (p21, p27, Rb, Raf-1, p-Raf-1, Erk1/2 and p-Erk1/2). The co-immunoprecipitation assay was used to explore the interaction between Mfn2 and Ras. The results showed that the overexpression of Mfn2 inhibited the proliferation of the HELF and induced the cell cycle arrest at the G0/G1 phase. Meanwhile, Mfn2 also inhibited the expression of collagen I, p-Erk and p-Raf-1. In addition, an interaction between Mfn2 and Ras existed in the HELF. This study suggests that the overexpression of Mfn2 can decrease the proliferation of HELF in ARDS, which was associated with the inhibition of the RAS-RAF-1-ERK1/2 pathway. The results may offer a potential therapeutic intervention for patients with ARDS.Cigarette smoking contributes to the development of pulmonary artery hypertension (PAH). As the basic pathological change of PAH, pulmonary vascular remodeling is considered to be related to the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the molecular mechanism underlying this process remains not exactly clear. The aim of this research was to study the molecular mechanism of PASMCs proliferation induced by smoking. Human PASMCs (HPASMCs) were divided into 6 groups 0% (control group), cigarette smoking extract (CSE)-treated groups at concentrations of 0.5%, 1%, 2%, 5%, 10% CSE respectively. link2 HPASMCs proliferation was observed after 24 h. HPASMCs were divided into two groups 0 (control group), 0.5% CSE group. The mRNA and protein expression levels of transient receptor potential channel 1 (TRPC1) and cyclin D1 in HPASMCs after CSE treatment were respectively detected by RT-PCR and Western blotting. The intracellular calcium ion concentration was measured by the calcium prob as compared with those in the negative control group (P less then 0.05). It was concluded that low concentration of CSE can promote the proliferation of HPASMCs, while high concentrations of CSE inhibit HPASMCs proliferation. link3 These findings suggested that CSE induced proliferation of HPASMCs at least in part via TRPC1-mediated cyclin D1 expression.Inflammation plays an important role in the development of several cancers. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), are associated with the induction of inflammation. Chronic inflammation contributes to the progression of cancer through several mechanisms, including increased cytokine production and activation of transcription factors, such as nuclear factor-κB (NF-κB). Zerumbone (ZER), a component of subtropical ginger (Zingiber zerumbet Smith), seems to have anti-inflammatory, anti-cancer, and antioxidant activities. In this study, we aimed to explore the protective function and mechanisms of ZER against TNF-α-induced cancer-promoting cytokines. We found that the viability of stimulated human fibroblast cell lines was reduced after treatment with ZER (IC50=18 µmol/L), compared to un-stimulated fibroblasts (IC50=40 µmol/L). Besides, ZER inhibited mRNA expression and protein secretion of transforming growth factor-β (TGF-β), interleukin-33 (IL-33), monocyte chemoattractant protein-1 (MCP-1), and stromal cell-derived factor 1 (SDF-1), which were produced by TNF-α-induced fibroblasts, as measured by quantitative real time-PCR (qRT-PCR) and ELISA assays. The mRNA expression levels of TGF-β, IL-33, SDF-1, and MCP-1 showed 8, 5, 2.5, and 4-fold reductions, respectively. Moreover, secretion of TGF-β, IL-33, SDF-1, and MCP-1 was reduced to 3.65±0.34 ng/mL, 6.3±0.26, 1703.6±295.2, and 5.02±0.18 pg/mL, respectively, compared to the untreated group. In addition, the conditioned media (CM) of TNF-α-stimulated fibroblasts increased the NF-κB expression in colorectal cancer cell lines (HCT-116 and Sw48), while in the vicinity of ZER, the expression of NF-κB was reversed. Considering the significant effects of ZER, this component can be used as an appropriate alternative herbal treatment for cancer-related chronic inflammation.Glioblastoma multiforme, an intrusive brain cancer, has the lowest survival rate of all brain cancers. The chemotherapy utilized to prevent their proliferation and propagation is limited due to modulation of complex cancer signalling pathways. These complex pathways provide infiltrative and drug evading properties leading to the development of chemotherapy resistance. Therefore, the development and discovery of such interventions or therapies that can bypass all these resistive barriers to ameliorate glioma prognosis and survival is of profound importance. Medicinal plants are comprised of an exorbitant range of phytochemicals that have the broad-spectrum capability to target intrusive brain cancers, modulate anti-cancer pathways and immunological responses to facilitate their eradication, and induce apoptosis. These phytocompounds also interfere with several oncogenic proteins that promote cancer invasiveness and metastasis, chemotherapy resistance and angiogenesis. These plants are extremely vital for promising anti-glioma therapy to avert glioma proliferation and recurrence. In this review, we acquired recent literature on medicinal plants whose extracts/bioactive ingredients are newly exploited in glioma therapeutics, and also highlighted their mode of action and pharmacological profile.Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson's disease (PD) with mild cognitive impairment (MCI) is a focus in resting-state functional MRI (rs-fMRI) studies. This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis. Using group independent component analysis (ICA) on rs-fMRI data acquired from 30 participants (14 healthy controls and 16 PD patients with MCI), 16 RSNs were identified, and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups. Compared to controls, patients with PD showed decreased functional connectivity within putamen network, thalamus network, cerebellar network, attention network, and self-referential network, and increased functional connectivity within execution network. Globally disturbed, mostly increased functional connectivity of FNC was observed in PD group, and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs. Cerebellar network showed decreased functional connectivity with caudate network, insular network, and self-referential network. In general, decreased functional connectivity within RSNs and globally disturbed, mostly increased functional connectivity of FNC may be characteristics of PD. Increased functional connectivity within execution network may be an early marker of PD. The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN, contributing to the understanding of the neural mechanism of PD.This study aimed to elucidate the molecular mechanisms by which berberine protects against cerebral ischemia/reperfusion (I/R) injury. The oxygen-glucose deprivation/reperfusion (OGD/R) PC12 model was established. Cell counting kit-8 (CCK-8) was used to detect the toxicity of berberine and the viability of PC12 cells. Hoechst 33258 staining and flow cytometry were used to observe the nuclear morphology, and changes of apoptosis and reactive oxygen species (ROS), respectively. Western blotting and immunofluorescence assay were employed to detect autophagy-related proteins [microtubule-associated protein 1A/1B-light chain 3 (LC3), P62/SQSTM-1, Beclin-1] and endoplasmic reticulum (ER) stress-related markers [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Bcl-2-associated X (Bax) and cleaved caspase-3]. The GFP-RFP-LC3 adenovirus was used to assay the change of autophagic flux. Our results showed that berberine could increase the viability of PC12 cells, decrease the concentrations of ROS after OGD/R treatment, and suppress OGD/R-induced ER stress and autophagy. Moreover, the results revealed the involvement of the mammalian target of rapamycin (mTOR) pathway in the induction of autophagy, and berberine could activate the phosphorylation of mTOR and thus mitigate autophagy. In conclusion, our study suggested that berberine may protect against OGD/R-induced apoptosis by regulating ER stress and autophagy, and it holds promises in the treatment of cerebral I/R injury.Alzheimer's disease (AD), also defined as a tauopathology, is a common neurodegenerative disease. Hyper-phosphorylation, cleavage or truncation, and aggregation of tau contribute to AD. Thus, targeting the post-translational modifications on tau may be a therapeutic strategy to treat AD. This study understood how cornel iridoid glycoside (CIG) affects tau post-translational modifications and synaptic abnormalities. The 10-month old P301S tau transgenic mice were given CIG at 100 and 200 mg/kg every day orally for 1 month. Hyperphosphorylated and truncated tau, synapse-associated proteins and glutamatergic receptors were all detected using Western blotting. The interactions between Morroniside (MOR) or Loganin (LOG) and tau were detected using Autodock and Surface Plasmon Resonance (SPR). The effects of CIG on the aggregation of tau were investigated using a cell-free system. CIG attenuated tau hyperphosphorylation at Thr205, Ser212, Ser262, Thr231 and Ser235 (AT180), but had no effect on tau truncation in the brains of 10-month old P301S mice. Binding free energies and interactions revealed that MOR and LOG bound with tau. We also found that CIG upregulated synapse-associated proteins such as PSD-95, syntaxin1A and synaptotagmin. In addition, CIG restored N-methyl-D-aspartic acid receptor and glutamate receptor levels. CIG improves post-translational modification of tau as well as synaptic abnormalities. The data presented here reveal that CIG may be used in the treatment of AD.rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer's disease (AD). Besides cognitive impairments, rTg4510 mice also show abnormal hyperactivity behavior. Cornel iridoid glycoside (CIG) is an active ingredient extracted from Cornus officinalis, a traditional Chinese herb. The purpose of the present study was to investigate the effects of CIG on the emotional disorders such as hyperactivity, and related mechanisms. The emotional hyperactivity was detected by locomotor activity test and Y maze test. Immunofluorescent and immunohistochemical analyses were conducted to measure neuron loss and phosphorylated tau. Western blotting was used to detect the expression of related proteins. The results showed that intragastric administration of CIG for 3 months decreased the hyperactivity phenotype, prevented neuronal loss, reduced tau hyperphosphorylation and aggregation in the amygdala of rTg4510 mice. Meanwhile, CIG alleviated the synaptic dysfunction by increasing the expression of N-methyl-D-aspartate receptors (NMDARs) subunits GluN1 and GluN2A and αamino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunits GluA1 and GluA2, and increased the level of phosphorylated Ca2+/calmodulin dependent protein kinase II α (p-CaMK IIα) in the brain of rTg4510 mice.