Mitochondrial dysfunction and oxidative stress are thought to play a dominant role in the pathogenesis of Parkinson’s disease (PD). Mogroside V (MV), extracted from
Siraitia grosvenorii
, exhibits ...antioxidant-like activities. The aim of this study was to investigate the function of MV in neuroprotection in PD and to reveal its mechanism of action. To that end, we firstly set up mice models of PD with unilateral striatum injection of 0.25 mg/kg rotenone (Rot) and co-treated with 2.5 mg/kg, 5 mg/kg, and 10 mg/kg MV by gavage. Results showed that Rot-induced motor impairments and dopaminergic neuronal damage were reversed by treatment of 10 mg/kg MV. Then, we established cellular models of PD using Rot-treated SH-SY5Y cells, which were divided into six groups, including control, Rot, and co-enzyme Q10 (CQ10), as well as MV groups, MV25, MV50, and MV100 treated with 25 μM, 50 μM, and 100 μM MV doses, respectively. Results demonstrated that MV effectively attenuates Rot neurotoxicity through a ROS-related intrinsic mitochondrial pathway. MV reduced overproduction of reactive oxygen species (ROS), recovered the mitochondrial membrane potential (MMP), and increased the oxygen consumption rate and adenosine triphosphate (ATP) production in a dose-dependent manner. Hence, treatment with MV led to a reduction in the number of apoptotic cells, as reflected by Annexin-V/propidium iodide co-staining using flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. In addition, the Sirtuin3 (SIRT3) protein level and activity were decreased upon exposure to Rot both in substantia nigra (SN) of mice and SH-SY5Y cells. SIRT3 impairment hyperacetylated a key mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2). MV alleviates SIRT3 and SOD2 molecular changes. However, after successfully inhibiting SIRT3 by its specific inhibitor 3-1H-1, 2, 3-triazol-4-yl pyridine (3TYP), MV was not able to reduce ROS levels, reverse abnormal MMP, or decrease apoptotic cells. Motor impairments and dopaminergic neuronal injury in the SN were alleviated with the oral administration of MV in Rot-treated PD mice, indicating a relationship between protection against defective motility and preservation of dopaminergic neurons. Therefore, we conclude that MV can alleviate Rot-induced neurotoxicity in a PD model, and that SIRT3 may be an important regulator in the protection of MV.
(1) Introduction: Previous studies have found that diet can change gut microbiota, thereby affecting metabolic health. However, research on gestational diabetes mellitus (GDM) is still limited. Our ...study aimed to explore the mediating role of gut microbiota in the relationship between dietary patterns and GDM. (2) Methods: In this case-control study, 107 women with GDM at 24–28 weeks of gestation and 78 healthy pregnant women were enrolled. A semi-quantitative food frequency questionnaire (FFQ) was used to assess dietary intake over the previous month. Mediation analysis was performed to explore the link between dietary patterns, gut microbiota, and GDM. (3) Results: Among the five dietary patterns extracted, the high group (factor scores ≥ −0.07) of the vegetables-fruits dietary pattern had a 67% lower risk of developing GDM compared to the low group (factor scores < −0.07) (OR: 0.33; 95% CI: 0.15–0.74). In addition, a significant alteration was observed in gut microbiota composition among GDM pregnant women. Mediation analysis showed that the Lachnospiraceae family, Blautia, and Ruminococcus genus partially mediated the effect of vegetables-fruits dietary pattern on GDM, explaining 45.81%, 44.33%, and 31.53% of the association, respectively. (4) Conclusions: Adherence to vegetables-fruits dietary patterns during pregnancy may reduce the risk of GDM by altering gut microbiota composition.
Reactive astrogliosis is an early event in Alzheimer's disease (AD) brain and plays a key role in synaptic degeneration in AD development. Zinc accumulates in extracellular fraction and synaptosomes ...in AD human brains with its effect on reactive astrocytes remaining unknown. Through Western blotting, Quantitative polymerase chain reaction (qPCR), and immunofluorescence detection on primary astrocytes treated by zinc and/or zinc chelator, we revealed that zinc induced harmful A1‐type reactive astrogliosis in cultured primary astrocytes; the latter, promoted synaptic degeneration in primary neurons. The mechanism investigation showed that zinc induced activation of extracellular regulated protein kinase (ERK) and Janus kinase 2 (JAK2), which phosphorylated signal transduction and transcription activator 3 (Stat3) at serine 727 (S727‐Stat3) and tyrosine 705 (Y705‐Stat3), respectively, resulting in activation of Stat3. Stat3 phosphorylation at S727 by ERK plays a key role in zinc‐induced astrogliosis. These data imply a new molecular mechanism of reactive astrogliosis in AD, in which excessive zinc activates Stat3 through up‐regulating ERK signaling pathway.
Zinc activates extracellular regulated protein kinases (ERK) to phosphorylate signal transduction and transcription activator 3 (Stat3) at serine 727 (S727), resulting in Stat3 activation and A1‐type astrogliosis. Zinc also activates Janus kinase 2 (JAK2) to induce phosphorylation of Stat3 at tyrosine 705 (Y705), but Stat3 phosphorylation at this site is not indispensable for astrocytes activation by zinc. The pro‐inflammatory factors released by active astrocytes promote synaptic degeneration in neurons.
Cisplatin resistance is a major cause of treatment failure in advanced ovarian cancer. The limited evidence shows the paradoxical regulation of miR-205 on chemotherapy resistance in cancer. Herein, ...we found that miR-205-5p was enormously increased in cisplatin-resistant C13K ovarian cancer cells compared with its cisplatin-sensitive OV2008 parental cells using miRNA microarrays, which was further verified by quantitative PCR. Furthermore, we confirmed that inhibition of miR-205-5p upregulated PTEN and subsequently attenuated its downstream target p-AKT, which inversed C13K cells from cisplatin resistance to sensitivity. Our data suggest that miR-205-5p contributes to cisplatin resistance in C13K ovarian cancer cells may via targeting PTEN/AKT pathway.
Efficient and precise circulating tumor cells' (CTCs) capture and release with minimal effect on cell viability for CTCs' analysis are general requirements of CTCs' detection device in clinical ...application. However, these two essential factors are difficult to be achieved simultaneously.
In order to reach the aforementioned goal, we integrated multiple strategies and technologies of staggered herringbone structure, nanowires' substrate, peptides, enzymatic release, specific cell staining, and gene sequencing into microfluidic device and the sandwich structure peptide-silicon nanowires' substrate was termed as Pe-SiNWS.
The Pe-SiNWS demonstrated excellent capture efficiency (95.6%) and high release efficiency (92.6%). The good purity (28.5%) and cell viability (93.5%) of CTCs could be obtained through specific capture and biological release by using Pe-SiNWS. The good purity of CTCs facilitated precise and quick biological analysis, and five types of KRAS mutation were detected in 16 pancreatic cancer patients but not in healthy donors.
The results proved that the effective capture, minor damage release, and precise analysis of CTCs could be realized simultaneously by our novel strategy. The successful clinical application indicated that our work was anticipated to open up new opportunities for the design of CTC microfluidic device.
Due to the multifactorial aetiology and unpredictable long-term stability, skeletal anterior open bite (SAOB) is one of the most intractable conditions for orthodontists. The abnormal orofacial ...myofunctional status (OMS) may be a major risk factor contributing to the development and relapse of SAOB. This study is aimed at evaluating the OMS and the efficacy of orofacial myofunctional therapy (OMT) alone for SAOB subjects.
Eighteen adolescents with SAOB (4 males, 14 females; age: 12-18 years) and eighteen adolescents with normal occlusion (2 males, 16 females; age: 12-18 years) were selected. The electromyographic activity (EMGA) associated with mastication and closed mouth state was measured. Lateral cephalography was used to evaluate craniofacial morphology. Wilcoxon signed rank tests and t-tests were performed to evaluate myofunctional and morphological differences. Pearson or Spearman correlation analysis was used to investigate the correlations between EMGA and morphological characteristics. SAOB subjects were given OMT for 3 months, and the EMGA was compared between before and after OMT.
During rest, anterior temporalis activity (TAA) and mentalis muscle activity (MEA) increased in SAOB subjects, but TAA and masseter muscle activity (MMA) decreased in the intercuspal position (ICP); and upper orbicularis activity (UOA) and MEA significantly increased during lip sealing and swallowing (P < 0.05). Morphological evaluation revealed increases in the FMA, GoGn-SN, ANS-Me, N-Me, L1-MP, U6-PP, and L6-MP and decreases in the angle of the axis of the upper and lower central incisors and OB in SAOB subjects (P < 0.05). TAA, MMA and anterior digastric activity (DAA) in the ICP were negatively correlated with vertical height and positively correlated to incisor protrusion. MEA was positively correlated with vertical height and negatively correlated with incisor protrusion; and the UOA showed a similar correlation in ICP, during sealing lip and swallowing. After SAOB subjects received OMT, MEA during rest and TAA, MMA and DAA in the ICP increased, while UOA and MEA decreased (P < 0.05).
SAOB subjects showed abnormal OMS features including aberrant swallowing patterns and weak masticatory muscles, which were interrelated with the craniofacial dysmorphology features including a greater anterior facial height and incisor protrusion. Furthermore, OMT contributes to OMS harmonization, indicating its therapeutic prospect in SAOB.
Aging is a major risk factor contributing to neurodegeneration and dementia. However, it remains unclarified how aging promotes these diseases. Here, we use machine learning and weighted gene ...co-expression network (WGCNA) to explore the relationship between aging and gene expression in the human frontal cortex and reveal potential biomarkers and therapeutic targets of neurodegeneration and dementia related to aging. The transcriptional profiling data of the human frontal cortex from individuals ranging from 26 to 106 years old was obtained from the GEO database in NCBI. Self-Organizing Feature Map (SOM) was conducted to find the clusters in which gene expressions downregulate with aging. For WGCNA analysis, first, co-expressed genes were clustered into different modules, and modules of interest were identified through calculating the correlation coefficient between the module and phenotypic trait (age). Next, the overlapping genes between differentially expressed genes (DEG, between young and aged group) and genes in the module of interest were discovered. Random Forest classifier was performed to obtain the most significant genes in the overlapping genes. The disclosed significant genes were further identified through network analysis. Through WGCNA analysis, the greenyellow module is found to be highly negatively correlated with age, and functions mainly in long-term potentiation and calcium signaling pathways. Through step-by-step filtering of the module genes by overlapping with downregulated DEGs in aged group and Random Forest classifier analysis, we found that
MAPT
,
KLHDC3, RAP2A
,
RAP2B
,
ELAVL2
, and
SYN1
were co-expressed and highly correlated with aging.
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Emerging evidence has suggested that long noncoding RNAs (lncRNAs) play vital roles in various biological ...processes of cancers, such as cell proliferation, migration, invasion, and apoptosis. As reported previously, long intergenic non-protein coding RNA 284 (LINC00284) is an important regulator in multiple cancers. However, the biological role, as well as regulatory mechanism of LINC00284 in OSCC, has not been investigated. In our study, RT-qPCR results indicated that LINC00284 was significantly upregulated in OSCC tissues and cells. Moreover, loss-of-function experiments demonstrated that LINC00284 downregulation suppressed cell proliferation and migration and facilitated cell apoptosis. Mechanistically, we found that LINC00284 sponged microRNA 211-3p (miR-211-3p) to upregulate MAF bZIP transcription factor G (MAFG) expression in OSCC cells. Additionally, LINC00284 interacted with FUS protein to increase KAZN mRNA stability. Functional assays showed that either MAFG or KAZN overexpression promoted the malignant behaviors of OSCC cells. Through a series of rescue assays, we found that the inhibitory effect of silencing LINC00284 on OSCC cells can be reversed by upregulated MAFG and KAZN. Overall, silencing LINC00284 inhibits the malignant characteristics of OSCC cells by downregulating MAFG and inhibiting the binding of FUS to KAZN mRNA.
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