Abernathyrosen0689

Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand-receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.Introduction Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective To assess the safety of inulin and sinistrin use in France. Methods We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration's impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells' presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.Background Keeping in view the high recurrence rate and risk of ischemic stroke, combinatorial therapy involving traditional Chinese medicine (TCM) with conventional Western medicine (WM) is receiving wider scientific attention. Thus, a systematical analysis was made to explore the efficacy of TCM+WM in the long-term secondary prevention for patients with ischemic stroke. Methods Qualified inclusion and exclusion criteria were set up beforehand, and two researchers independently read the articles, extracted data, and evaluated the quality of included articles according to Cochrane Reviewer's Handbook 5.1 method. For the sake of comprehensive data acquisition, seven databases from the time of their establishment to May 5, 2021, have been searched completely. Additionally, pairwise meta-analysis was made to compare TCM+WM vs. WM, and network meta-analysis was conducted by frequentist random effects models for the comparison of different kinds of TCM+WM via indirect evidence. The primary outcomes defined were retive effects for recurrent stroke, NIHSS, and all-cause mortality. There was no significant difference in the comparisons of AEs; however, this may arise from the lack of sufficient data. Conclusion According to our systematical analysis, MXK+WM and NST+WM had relatively good secondary prevention effects for patients with ischemic stroke regarding recurrent stroke, NIHSS, and all-cause mortality. Nevertheless, better, high-quality, large-sample randomized clinical trials (RCTs) are required to verify our conclusions in the future. Systematic Review Registration [https//inplasy.com/inplasy-2021-5-0036/], identifier [INPLASY202150036].Bacterial outer membrane vesicles (OMVs) have recently drawn a great deal of attention due to their therapeutic efficiency and ability to target specific cells. In the present study, we sought to probe engineered OMVs as novel and promising carriers to target breast cancer cells. Following the fusion of the affiEGFR-GALA structure to the C-terminal of ClyA as an anchor protein, the ClyA-affiEGFR-GALA construct was successfully expressed on the surface of ∆msbB/∆pagP E. coli W3110-derived OMVs. Morphological features of the engineered and wild-type OMVs were identical. The engineered OMVs induced no endotoxicity, cytotoxicity, or immunogenicity, indicating the safety of their application. MLN8054 purchase These OMVs could specifically bind to EGF receptors of MDA-MB-468 cells expressing high levels of EGFR and not to those with low levels of EGFR (HEK293T cells). Interestingly, despite a lower binding affinity of the engineered OMVs relative to the positive control Cetuximab, it was strong enough to identify these cells. Moreover, confocal microscopy revealed no uptake of the modified OMVs by the EGFR-overexpressing cells in the presence of EGFR competitors. These results suggest that OMVs might internalize into the cells with EGF receptors, as no OMVs entered the cells with any EGFR expression or those pretreated with EGF or Cetuximab. Regarding the EGFR-binding affinity of the engineered OMVs and their cellular uptake, they are presented here as a potential carrier for cell-specific drug delivery to treat a wide variety of cancer cells. Interestingly, the engineered OMVs are capable of reaching the cytoplasm while escaping the endosome due to the incorporation of a fusogenic GALA peptide in the construct.Objectives Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2. Methods and results Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60-70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PS inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.Gonggan (Citrus reticulata Blanco var. gonggan) is one of the most popular citruses. In this study, the effect of Gonggan peel extract (GPE) on gastric injury was investigated. The components in GPE were analysed by HPLC and the gastric injury model in mice was established by ethanol/hydrochloric acid. After treatment by GPE, the pathological changes of gastric tissue were observed by optical microscope. The levels of oxidative stress and inflammation were measure by kit. And the mRNA expression of related gene was determined by qPCR assay. HPLC result showed GPE mainly contained the flavonoids narirutin, hesperidin, nobiletin, tangeretin and 5-demethylnobiletin. Morphological and pathological analysis of gastric tissue revealed that GPE could relieve gastric injury. Also, GPE increased the levels of SOD, GSH-Px, and CAT and decreased the level of MDA. Moreover, GPE decreased the levels of the inflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6 to suppress inflammation. In addition, the q-PCR results showed that GPE upregulated the mRNA expression of SOD1, SOD2, γ-GCS, GSH-Px, CAT, and IκBα and downregulated the mRNA expression of NF-κB. In conclusion, GPE alleviated gastric injury caused by ethanol/hydrochloric acid by inhibiting oxidative stress and the inflammatory response. The mechanism by which GPE protects gastric tissues may involve the antioxidative pathway. Therefore, GPE has great potential to be developed as a product to prevent gastric injury.Endogenous nitro-fatty acids (NFA) are potent electrophilic lipid mediators that exert biological effects in vitro and in vivo via selective covalent modification of thiol-containing target proteins. The cytoprotective, anti-inflammatory, and anti-tumorigenic effects of NFA in animal models of disease caused by targeted protein nitroalkylation are a valuable basis for the development of future anti-phlogistic and anti-neoplastic drugs. Considering the complexity of diseases and accompanying comorbidities there is an urgent need for clinically effective multifunctional drugs. NFA are composed of a fatty acid backbone containing a nitroalkene moiety triggering Michael addition reactions. However, less is known about the target-specific structure-activity relationships and selectivities comparing different NFA targets. Therefore, we analyzed 15 NFA derivatives and compared them with the lead structure 9-nitro-oleic acid (9NOA) in terms of their effect on NF-κB (nuclear factor kappa B) signaling inhibition, induction of Nrf-2 (nuclear factor erythroid 2-related factor 2) gene expression, sEH (soluble epoxide hydrolase), LO (lipoxygenase), and COX-2 (cyclooxygenase-2) inhibition, and their cytotoxic effects on colorectal cancer cells.