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The microglia-mediated inflammatory response is one of the main causes of brain tissue damage after stroke. In recent years, it has been reported that autophagy in microglia played an important role in inflammatory response after stroke. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate autophagy and inflammatory in microglia; however, the detailed mechanisms remain unclear. This study aimed to investigate whether autophagy regulates inflammatory is associated with TRPV1. Model of oxygen and glucose deprivation/reoxygenation (OGD/R) was established in vitro to induce cerebral ischemia-reperfusion injury (I/R). siRNA of Atg5, inhibitors, and agonists of both autophagy and TRPV1 were involved in our study. Autophagy was assayed by immunofluorescence staining LC-3 and autophagosome was observed using transmission electron microscopy (TEM). Autophagy/inflammation-related markers as Atg5, LC-3II/LC-3I, Beclin-1, NLRP3, IL-1β, and Caspase-1 were also measured in the present study. Results indicated that I/R injury-induced inflammatory injury may be impeded by inhibition of autophagy, and TRPV1 could suppress OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on inflammatory response was attenuated when the autophagy was blocked. These findings suggested that TRPV1 exhibits an anti-inflammatory effect on OGD/R-induced microglia, which was at least correlated with the anti-autophagy action of TRPV1 partially.

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.

Apigenin is a natural flavonoid found in several dietary plant foods as vegetables and fruits. To investigate potential anti-ischemia/reperfusion injury properties of apigenin in vitro, cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of apigenin was also explored in rats after middle cerebral artery occlusion/reperfusion (MCAO/R) via neurobehavioral scores, pathological examination, and measurement of markers involved in ischemia/reperfusion injury. Data in vitro indicated that apigenin could prompt cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy by affecting Caveolin-1/VEGF, Bcl-2, Caspase-3, Beclin-1, and mTOR expression. Results in vivo showed that apigenin significantly reduced neurobehavioral scores and volume of cerebral infarction while prompting vascular endothelial cell proliferation by upregulating VEGFR2/CD34 double-labeling endothelial progenitor cell (EPC) number and affecting Caveolin-1, VEGF, and eNOS expression in brain tissue of MCAO/R rats. All the data suggested that apigenin may be protective for the brain against ischemia/reperfusion injury by alleviating apoptosis and autophagy, promoting cell proliferation in HBMVECs of OGD/R, and attenuating brain damage and improved neurological function in rats of MCAO/R through the Caveolin-1/VEGF pathway.

In the present study, we aimed to elucidate whether apigenin contributes to the induction of angiogenesis and the related mechanisms in cell hypoxia-reoxygenation injury. The role of apigenin was examined in human umbilical vein endothelial cell (HUVEC) viability, migration and tube formation in vitro. To investigate the related mechanisms, we used caveolin-1 short interfering RNA. The viability of HUVECs was measured using Cell Counting Kit-8 assays, HUVEC migration was analyzed by crystal violet staining, and a tube formation assay was performed using the branch point method. Expression of caveolin-1, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) in HUVECs was examined by polymerase chain reaction and western blotting. Our data revealed that apigenin induced angiogenesis in vitro by increasing the tube formation ability of HUVECs, which was counteracted by caveolin-1 silencing. Compared to the NC group, Caveolin-1 and eNOS expression was upregulated by apigenin, whereas compared to the NC group, eNOS expression was increased upon caveolin-1 silencing. The expression of VEGF was increased by treatment with apigenin; however, compared to the NC group, caveolin-1 silencing did not affect VEGF expression, and apigenin did not increase VEGF expression in HUVECs after caveolin-1 silencing. These data suggest that apigenin may be a candidate therapeutic target for stroke recovery by promoting angiogenesis via the caveolin-1 signaling pathway.

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.

A previous in vivo study demonstrated that intracerebroventricular injection of basic fibroblast growth factor (bFGF) in middle cerebral artery occlusion rats increased the expression of caveolin-1 (cav-1) and vascular endothelial growth factor (VEGF) in cerebral ischemia penumbra. Because astrocytes are the largest population in the brain, the aim of this in vitro study was to investigate the influence of bFGF on cav-1 and VEGF expression in rat astrocytes following oxygen glucose deprivation/reoxygenation (OGD/R). For this, an ischemic model in vitro of oxygen glucose deprivation lasting for 6 h, followed by 24 h of reoxygenation was used. Primary astrocytes from newborn rats were pre-treated with siRNA targeting bFGF before OGD/R. Cell viability was measured by a CCK-8 assay. The protein and mRNA expressions of bFGF, cav-1, and VEGF were evaluated by western blotting, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction. The results showed that OGD/R reduced cell viability, which was decreased further following bFGF knockdown; however, restoring bFGF improved cell survival. A cav-1 inhibitor abrogated the effect of bFGF on cell viability. The expression levels of bFGF mRNA, bFGF protein, cav-1 mRNA, cav-1 protein, and VEGF protein were higher in OGD/R astrocytes. bFGF knockdown markedly decreased the expression levels of cav-1 mRNA, cav-1 protein, and VEGF protein, which were effectively reversed by exogenous bFGF treatment. Moreover, exogenous bFGF treatment significantly increased the expression levels of cav-1 mRNA, cav-1 protein, and VEGF protein in OGD/R astrocytes; however, a cav-1 inhibitor abolished the effect of bFGF on VEGF protein expression. These results suggested that bFGF may protect astrocytes against ischemia/reperfusion injury by upregulating caveolin-1/VEGF signaling pathway.

Dengue fever (DF) is one of the most rapidly spreading diseases in the world, and accurate forecasts of dengue in a timely manner might help local government implement effective control measures. To obtain the accurate forecasting of DF cases, it is crucial to model the long-term dependency in time series data, which is difficult for a typical machine learning method. This study aimed to develop a timely accurate forecasting model of dengue based on long short-term memory (LSTM) recurrent neural networks while only considering monthly dengue cases and climate factors. The performance of LSTM models was compared with the other previously published models when predicting DF cases one month into the future. Our results showed that the LSTM model reduced the average the root mean squared error (RMSE) of the predictions by 12.99% to 24.91% and reduced the average RMSE of the predictions in the outbreak period by 15.09% to 26.82% as compared with other candidate models. The LSTM model achieved superior performance in predicting dengue cases as compared with other previously published forecasting models. Moreover, transfer learning (TL) can improve the generalization ability of the model in areas with fewer dengue incidences. The findings provide a more precise forecasting dengue model and could be used for other dengue-like infectious diseases.

, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from . This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of -derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics. C57 mice experienced facilitated wound healing through -derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation. DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1β and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs' efficacy in suppressing IL-1β expression, enhancing wound healing. Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1β overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1β expression, accelerating skin wound tissue repair.

Skin wound healing is a multifaceted biological process involving dynamic interactions among various cells and signaling molecules. Angiogenesis is a key component of this repair process. Dendrobium officinale, a traditional medicinal plant, has shown therapeutic promise, particularly through its bioactive nanovesicles. This study investigates the therapeutic potential of Dendrobium officinale-derived nanovesicles (DDNVs) in regulating angiogenesis, inflammation, and tissue repair, to promote enhanced skin wound healing. A full-thickness mouse skin wound model was used to evaluate the in vivo effects of DDNVs on wound closure, angiogenesis, and collagen remodeling. Histological staining (H&E and Masson’s trichrome) and CD31 immunofluorescence were performed. In vitro, DDNVs were tested on Human umbilical vein endothelial cells(HUVECs) and Human keratinocyte cells (HaCaT) cells to assess cell proliferation, migration, and angiogenesis. Confocal microscopy was used to track cellular uptake. Activation of the Akt/eNOS pathway and expression of key genes related to inflammation and matrix remodeling were evaluated by Western blotting and qPCR. DDNVs significantly accelerated wound healing and promoted angiogenesis in vivo, as evidenced by enhanced CD31 expression and collagen remodeling. In vitro, DDNVs entered cells efficiently and stimulated HUVEC and HaCaT proliferation and migration. This was accompanied by activation of the Akt/eNOS signaling pathway, increased expression of eNOS and VEGFR-2, upregulation of extracellular matrix(ECM) components (Vimentin, Fibronectin, COL1A1), and suppression of inflammatory markers such as ICAM-1 and IL-1β. DDNVs exhibit strong potential to enhance skin wound healing by promoting angiogenesis, improving tissue repair, and modulating inflammation. These findings support the clinical development of DDNVs as a novel, plant-derived nanotherapeutic for chronic wound treatment and skin regeneration.

Background Ovarian cancer (OC) is a highly lethal gynecological cancer. Olaparib maintenance therapy was effective and well-tolerated in pivotal RCTs. However, nationwide real-world safety information is limited in China. This multicenter, prospective, observational drug intensive monitoring study monitored the safety of olaparib in a largest-to-date, real-world Chinese OC cohort. Methods Eligible OC patients had received ≥ 1 dose of olaparib. Follow-up extended up to 30 days post-olaparib discontinuation or maximally for six months post-enrolment. Primary and secondary endpoints were adverse events (AEs) in all OC patients and in special populations (hepatically/renally impaired before olaparib treatment; aged > 65 years), respectively. Results By Jun 30, 2023, 799 patients from 33 sites were enrolled. By data cut-off (Dec 29, 2023), 796 patients treated with olaparib were analyzed. The median age was 55 years (range, 25–85). Of 796 patients, 490 (61.6%) were newly diagnosed and 306 (38.4%) had platinum-sensitive relapsed OC. AEs occurred in 343 (43.1%) patients, and 257 (32.3%) had treatment-related AEs. Anemia (19.2%) was the most common AE. Sixty-eight (8.5%) patients experienced grade ≥ 3 AEs, and 3 had AEs of special interest (AESIs; 0.4%; 1 myelodysplastic syndrome, 1 breast cancer, 1 pneumonitis). 45.2% (19/42) patients with hepatic impairment at baseline, 38.5% (5/13) with renal impairment at baseline and 38.6% (49/127) aged > 65 years experienced any AEs, respectively. No AESIs were reported in these subgroups. Conclusions In this largest-to-date, first prospectively enrolled, real-world Chinese OC cohort, olaparib demonstrated a well-tolerated and manageable safety profile (including in special populations) with appropriate management, regardless of treatment lines. No new safety signals were identified.