Mechanism of Litchi Semen Extract in Preventing Exercise-induced Muscle Damage Based on Network Pharmacology and in Vivo and in Vitro Experiments

Objective: Based on network pharmacology combined with the GEO database and in vivo and in vitro experiments to explore the potential mechanisms of litchi semen extract (LZH) for preventing exercise-induced muscle damage (EIMD). Methods: Hematoxylin-eosin (HE) staining and comparison of the levels of indicators of skeletal muscle damage in serum were performed to detect the effectiveness of LZH in preventing EIMD. The main active ingredients of LZH were searched through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database in conjunction with the published literature, and the targets corresponding to the active ingredients were found through the relevant websites, which were intersected with the EIMD-related targets obtained from the GEO database. The STRING database screened the intersected targets and finally enriched them for analysis. The results of the network pharmacology predictions were validated in vivo using the centrifugal exercise-induced EIMD mouse model and in vitro using the H2O2-induced C2C12 cell model. Results: In vivo experiments showed that skeletal muscle fiber cross-sectional area (P<0.05), creatine kinase (CK) (P<0.001) and lactate dehydrogenase (LDH) (P<0.01) were significantly reduced after the intervention of LZH. The results of network pharmacology showed that LZH had 14 active ingredients, corresponding to 367 targets. The GEO database obtained 1015 targets related to EIMD. The intersection of the two yielded 37 intersecting targets. The enrichment analysis demonstrated p53-mediated cell cycle arrest as the primary target for validation. In vivo experiments showed that LZH significantly reduced the expression of p53 (P<0.01), p21 (P<0.001), BCL2-associated X (Bax) (P<0.05), and the expression of Cyclin D1 (P<0.05), B-cell lymphoma-2 (Bcl-2) (P<0.05) expression was significantly increased. In vitro experiments showed that low and high dose pretreatment of LZH significantly decreased the expression of apoptosis (P<0.001), p53 (P<0.05), p21 (P<0.01, P<0.001) and increased the expression of Cyclin D1 (P<0.05, P<0.001). Conclusion: LZH attenuates EIMD, and its mechanism is closely related to the activation of G1 phase arrest and attenuation of apoptosis in skeletal muscle cells. The results suggest that LZH can be used as a nutritional supplement to prevent EIMD

Enhancing Textual Personality Detection toward Social Media: Integrating Long-term and Short-term Perspectives

Textual personality detection aims to identify personality characteristics by analyzing user-generated content toward social media platforms. Numerous psychological literature highlighted that personality encompasses both long-term stable traits and short-term dynamic states. However, existing studies often concentrate only on either long-term or short-term personality representations, without effectively combining both aspects. This limitation hinders a comprehensive understanding of individuals' personalities, as both stable traits and dynamic states are vital. To bridge this gap, we propose a Dual Enhanced Network(DEN) to jointly model users' long-term and short-term personality for textual personality detection. In DEN, a Long-term Personality Encoding is devised to effectively model long-term stable personality traits. Short-term Personality Encoding is presented to capture short-term dynamic personality states. The Bi-directional Interaction component facilitates the integration of both personality aspects, allowing for a comprehensive representation of the user's personality. Experimental results on two personality detection datasets demonstrate the effectiveness of the DEN model and the benefits of considering both the dynamic and stable nature of personality characteristics for textual personality detection.Comment: 11 pages, 9 figure

Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review

In mammals, gonadal somatic cell lineage differentiation determines the development of the bipotential gonad into either the ovary or testis. Sertoli cells, the only somatic cells in the spermatogenic tubules, support spermatogenesis during gonadal development. During embryonic Sertoli cell lineage differentiation, relevant genes, including WT1, GATA4, SRY, SOX9, AMH, PTGDS, SF1, and DMRT1, are expressed at specific times and in specific locations to ensure the correct differentiation of the embryo toward the male phenotype. The dysregulated development of Sertoli cells leads to gonadal malformations and male fertility disorders. Nevertheless, the molecular pathways underlying the embryonic origin of Sertoli cells remain elusive. By reviewing recent advances in research on embryonic Sertoli cell genesis and its key regulators, this review provides novel insights into sex determination in male mammals as well as the molecular mechanisms underlying the genealogical differentiation of Sertoli cells in the male reproductive ridge

Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence-like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca(2+)/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg(2+)-free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p-CaMKII; Thr-286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p-CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p-CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co-localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca(2+)/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg(2+)-free solution

Transformation of high moisture extrusion on pea protein isolate in melting zone during : From the aspects of the rheological property, physicochemical attributes and modification mechanism

Plant-based meat analogs are emerging products mainly produced by extruder. To reveal the “black box” processing mechanism of extrusion, the physicochemical and rheological properties of pea protein isolate (PPI) were evaluated at different extrusion temperatures (90 °C, 100 °C, 110 °C, 120 °C and 130 °C) and moisture contents (65% and 70%) by using rheological simulation and stop-operation. The results showed a gel-like PPI paste, which presented shear thinning gel-like behavior and strong elastic characteristics. The weaken strain overshoot behavior of the PPI paste transformed to a strong strain overshoot with temperature increased under large amplitude oscillation. The PPI molecules transformed from a spherical structure to a tangled fibrous network, the absolute zeta potential value increased, and the total SH decreased. The native-like secondary structures of PPI were lost, and the relatively rigid protein structure was broken with increasing temperature. The tertiary structure of the raw material is gradually lost, and the Trp residue is transferred from the spherical structure interior to the surface of the protein molecule. The protein subunits were not decomposed during the extrusion process, and although the thermal stability of the PPI was reduced, new cross-links of higher bond energy could be formed at higher temperatures. Moreover, a higher extrusion temperature and proper moisture content can result in partial unfolding and realignment of extruded PPI

Regulation of broad by the Notch pathway affects timing of follicle cell development

AbstractDuring Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets of the follicle cells. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to regulate the mitotic/endocycle (ME) switch. Here we report that broad (br), encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. Mutation of the Su(H) binding site leads to a significant reduction of brE reporter expression in follicle cells undergoing the endocycle. Chromatin immunoprecipitation results further confirm Su(H) binding to the br early enhancer. Consistent with its expression in follicle cells during midoogenesis, loss of br function results in a delayed entry into the endocycle. Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway

High-dose Vitamin C inhibits PD-L1 expression by activating AMPK in colorectal cancer

Vitamin C (VitC) has elicited considerable interest regarding its potential role in cancer therapy; however, its effects on tumor immunity remain unclear. In colorectal cancer (CRC), although anti-PD-1/PD-L1 therapies demonstrate promise, their efficacy is still constrained. Our prior research demonstrated that VitC can inhibit tumor growth by suppressing the Warburg effect. This study aims to explore the effects of high-dose VitC on PD-L1 expression in CRC, focusing on its underlying mechanisms and potential for enhancing immunotherapy. We found that VitC inhibits aerobic glycolysis in HCT116 cells while also downregulating PD-L1 expression. Further investigations indicated that this process is mediated by VitC's activation of AMPK, which downregulates HK2 and NF-κB, ultimately resulting in reduced PD-L1 expression and increased T cell infiltration. Notably, we observed that VitC and the PD-L1 monoclonal antibody atezolizumab exhibit comparable tumor-inhibiting abilities, and their combined use further enhances this efficacy. In conclusion, our results demonstrate that high-dose VitC activates AMPK, downregulates PD-L1 expression, mitigates immune evasion, and suppresses tumor growth. This provides a promising strategy for optimizing immunotherapy in CRC