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As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the lifetime risk of bone fragility, cardiovascular disease, and cognitive impairment. To investigate the effects of environmental pollutants on the occurrence of POI and explore its mechanism, we conducted a computer search for articles published in electronic databases by December 13, 2022. Three reviewers independently examined all included studies and scored the qualities of included studies using the Newcastle-Ottawa Scale criteria. In this meta-analysis, eight clinical studies as well as ten preclinical findings showed a pooled OR of 2.331 and 95% CI of 1.968–2.760. This confirms that environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. In addition, it is demonstrated from the results of this study that signaling pathway of calcium and PI3K Akt and Xpnpep2, Col1, Col3, Col4, Cx43, Egr3, Tff1, and Ptgs2 genes may all be involved in the process. Environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. [ABSTRACT FROM AUTHOR]

Tubulin-associated unit (tau) is an important microtubule-associated protein. The abnormal intracellular aggregation of tau has been strongly associated with Alzheimer's disease (AD). Accumulating evidence has conclusively demonstrated that tau is present in the cytoplasm of neurons and is also actively released into the extracellular space. However, the types of tau species that are released are unclear, as is the mechanism of their release by donor neurons and subsequent uptake by recipient neurons in AD. Understanding the underlying mechanisms of abnormal tau cell-to-cell transmission can provide novel insights into the etiology and pathogenesis of AD and can help identify new targets for the development of AD therapies focused on counteracting neurodegeneration or even preventing it. From this perspective, the present review focuses on recent advances in understanding the mechanisms regulating the levels of extracellular tau and discusses the role of such mechanisms in the propagation of tau-associated pathology. [ABSTRACT FROM AUTHOR]

Background: Diaphorase (DI) has received wide attention as the key anodic enzyme mediating the electron transfer and electric energy generation in enzymatic biofuel cells (EBFCs). Lowering the anodic pH may be a useful strategy for constructing high-performance in EBFCs. However, most DI suffered from the poor activity at low pHs. Therefore, it is necessary to modify the activity and its acidic tolerance to further improve the performance of the EBFC. Results: This paper attempts to improve the enzyme activity of DI originated from Geobacillus stearothermophilus under acidic conditions through directed evolution. Three rounds of random mutagenesis by error-prone PCR of the GsDI gene followed by high-throughput screening allowed the identification of the mutant 3–8 (H37Q, S73T, F105L, S68T, G61S, D74V) exhibiting a 4- or 7-fold increase in the catalytic activity at pH 5.4 or 4.5 compared to that of the wild type. And the pH stability of mutant 3–8 was significantly better than that of wild type and showed a 1.3 times higher in the stability at pH 5.4. The EBFC anode equipped with 0.5 mg of mutant 3–8 achieved a maximum current of 40 μA at pH 5.4, much higher than that with the same loading of the wild type enzyme. Conclusion: The GsDI has been improved in the specific activity and pH stability by directed evolution which leads to the improvement of the EBFC performance. Also, the enlarged catalytic channel of mutant and decreased B-factor may be beneficial for the activity and stability. These results suggest that this engineered DI will be a useful candidate for the construction of enhanced EBFCs. [ABSTRACT FROM AUTHOR]

Exercise has been regarded as an effective rehabilitation strategy to facilitate motor and cognitive functional recovery after stroke, even though the complex effects associated with exercise-induced repair of cerebral ischemic injury are not fully elucidated. The enhancement of angiogenesis and neurogenesis, and the improvement of synaptic plasticity following moderate exercise are conducive to functional recovery after ischemic damage. Our previous studies have confirmed the angiogenesis and neurogenesis through the caveolin-1/VEGF pathway in MCAO rats. As an essential neurotrophic factor, BDNF has multiple effects on ischemic injury. In this study, we attempted to determine an additional mechanism of treadmill exercise-mediated motor and cognitive functional recovery through the caveolin-1/VEGF pathway associated with BDNF in the ischemic penumbra of MCAO mice. We found that mice exposed to treadmill exercise after the MCAO operation showed a significant up-regulation in expression of caveolin-1, VEGF, BDNF, synapsin I and CYFIP1 proteins, numbers of cells positive for BrdU/CD34, BDNF, BrdU/NeuN, BrdU/Synapsin I and CYFIP1 expression were increased, which support the reduction in neurological deficit and infarction volume, as well as improved synaptic morphology and spatial learning abilities, compared with the non-exercise mice. However, the caveolin-1 inhibitor, daidzein, resulted in increase in neurological deficit and infarction volume. The selective VEGFR2 inhibitor, PD173074, significantly induced larger infarction volume and neurological injury, and decreased the expression of BDNF in the ischemic penumbra. These findings indicate that exercise improves angiogenesis, neurogenesis and synaptic plasticity to ameliorate motor and cognitive impairment after stroke partially through the caveolin-1/VEGF pathway, which is associated with the coregulator factor, BDNF. [ABSTRACT FROM AUTHOR]

Using a model of middle cerebral artery occlusion (MCAO), we have previously demonstrated that treadmill exercise promotes angiogenesis in the ischemic penumbra through caveolin-1/VEGF signaling pathways. However, the function of caveolin-1/VEGF signaling in neurogenesis after MCAO has not been determined. In this study, we aimed to investigate the potential of treadmill exercise to promote neurogenesis after MCAO and whether caveolin-1/VEGF signaling pathways are involved. After MCAO, rats were subjected to a program of treadmill exercise. Daidzein (a specific inhibitor of caveolin-1 protein expression, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated neurogenesis. We found that the total protein expression of both caveolin-1 and VEGF was increased by exercise and consistent with the improved neurological recovery, decreased infarct volumes and increased 5-bromo-2′-deoxyuridine (BrdU) in the ipsilateral Subventricular zone (SVZ), as well as increased numbers of BrdU/DCX and BrdU/Neun-positive cells in the peri-infarct region. Furthermore, we observed that the treadmill exercise-induced increased VEGF expression, improved neurological recovery, decreased infarct volumes, increased BrdU/DCX and BrdU/Neun-positive cells were significantly inhibited by the caveolin-1 inhibitor. Our results indicate that treadmill exercise improves neurological recovery in ischemic rats, possibly by enhancement of SVZ-derived neural stem cell (NSC) proliferation, migration and differentiation in the penumbra. Moreover, caveolin-1/VEGF signaling is involved in exercise-mediated NSC migration and neuronal differentiation. [ABSTRACT FROM AUTHOR]