Perfluorooctane sulfonate (PFOS) is widely recognized as causing Sertoli cell injury and testicular toxicity in males. Icariin is a flavonoid from Epimedium, which effectively improves spermatogenesis disturbance induced by several factors in clinic. However, it is unclear whether icariin improves PFOS-induced testicular toxicity. In vivo, fifty-two male mice were randomly separated into four groups: normal control group, model group, and low and high doses of icariin-treated groups, with 13 mice in each group. Except for the normal control group, the mice in the model group and icariin-treated groups were administered PFOS (10 mg kg-1) by gavage daily for 28 consecutive days, and concurrently treated with a diet containing different doses of icariin (0, 5 or 20 mg kg-1). In vitro, TM4 cells were treated with 150 μM PFOS to induce Sertoli cell injury, and were then utilized for icariin treatment. Our results demonstrated that icariin attenuated PFOS-induced testicular toxicity by increasing the testicular, epididymal and seminal vesicle weights, epididymal and seminal vesicle indices, sperm parameters, and seminiferous epithelium height. In addition, icariin improved the PFOS-induced blood-testis barrier (BTB) disruption by alleviating the Sertoli cell junctional injury, but without affecting Sertoli cell numbers in the testis of mice. Moreover, icariin increased the expression levels of tight junction proteins (ZO-1, Occludin and Claudin-11) and gap junction proteins (CX43 and p-CX43), and decreased the expression levels of p-p38MAPK and matrix metalloproteinase 9 (MMP9) both in vivo and in vitro. Furthermore, alleviation of the Sertoli cell injury by icariin exerted similar effects as SB203580 (an inhibitor of p38MAPK) in TM4 cells. This study revealed that icariin effectively reduces PFOS-induced testicular toxicity by alleviating the Sertoli cell injury and downregulating the p38MAPK/MMP9 pathway, indicating that icariin may be an attractive dietary supplement for the intervention of PFOS-induced testicular dysfunction.
Functional magnetic resonance imaging (fMRI) has been used for evaluating residual brain function and predicting the prognosis of patients with severe traumatic brain injury (sTBI). This study aimed to integrate the fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) to investigate the mechanism and prognosis of patients with sTBI.Sixty-five patients with sTBI were included and underwent fMRI scanning within 14 days after brain injury. The patient's outcome was assessed using the Glasgow Outcome Scale-Extended (GOSE) at 6 months post-injury. Of the 63 patients who met fMRI data analysis standards, the prognosis of 18 patients was good (GOSE scores ≥ 5), and the prognosis of 45 patients was poor (GOSE scores ≤ 4). First, we apply fALFF to identify residual brain functional differences in patients who present different prognoses and conjoined it in regions of interest (ROI)-based FC analysis to investigate the residual brain function of sTBI at the acute phase of sTBI. Then, the area under the curve (AUC) was used to evaluate the predictive ability of the brain regions with the difference of fALFF and FC values.Patients who present good outcomes at 6 months post-injury have increased fALFF values in the Brodmann area (7, 18, 31, 13, 39 40, 42, 19, 23) and decreased FC values in the Brodmann area (28, 34, 35, 36, 20, 28, 34, 35, 36, 38, 1, 2, 3, 4, 6, 13, 40, 41, 43, 44, 20, 28 35, 36, 38) at the acute phase of sTBI. The parameters of these alterations can be used for predicting the long-term outcomes of patients with sTBI, of which the fALFF increase in the temporal lobe, occipital lobe, precuneus, and middle temporal gyrus showed the highest predictive ability (AUC = 0.883).We provide a compensatory mechanism that several regions of the brain can be spontaneously activated at the acute phase of sTBI in those who present with a good prognosis in the 6-month follow-up, that is, a destructive mode that increases its fALFF in the local regions and weakens its FC to the whole brain. These findings provide a theoretical basis for developing early intervention targets for sTBI patients.
Vesicle-associated membrane protein 2 (VAMP2, also known as synaptobrevin-2), encoded by VAMP2 in humans, is a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. VAMP2 combined with syntaxin-1A (SYX-1A) and synaptosome-associated protein 25 (SNAP-25) produces a force that induces the formation of fusion pores, thereby mediating the fusion of synaptic vesicles and the release of neurotransmitters. VAMP2 is largely unstructured in the absence of interaction partners. Upon interaction with other SNAREs, the structure of VAMP2 stabilizes, resulting in the formation of four structural domains. In this review, we highlight the current knowledge of the roles of the VAMP2 domains and the interaction between VAMP2 and various fusion-related proteins in the presynaptic cytoplasm during the fusion process. Our summary will contribute to a better understanding of the roles of the VAMP2 protein in membrane fusion.
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