The intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. Recent studies suggest multiple microRNAs (miRNAs) are ...involved in the neuroremodeling process. Targeted miRNAs delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. Here, we showed that modified exosomes, with rabies virus glycoprotein (RVG) fused to exosomal protein lysosome-associated membrane glycoprotein 2b (Lamp2b), could efficiently deliver miR-124 to the infarct site. Systemic administration of RVG-exosomes loaded with miR-124 promoted cortical neural progenitors to obtain neuronal identity and protect against ischemic injury by robust cortical neurogenesis. Our study suggests that RVG-exosomes can be utilized therapeutically for the targeted delivery of gene drugs to the brain, thus having great potential for clinical applications.
Our previous study found that mediator complex subunit 19 (Med19) is upregulated and involved in breast cancer tumorigenesis; however, the detailed effects and mechanism of Med19 in breast cancer ...require further study. In this study, we found that Med19 was obviously elevated in human breast cancer tissues, which was significantly associated with larger tumors, high-grade malignant features and poor prognosis. Furthermore, Med19 enhanced breast cancer cell proliferation, epithelial–mesenchymal transition, invasion and migration in vitro and in vivo. Med19 interacted with epidermal growth factor receptor (EGFR) and increased EGFR expression. Moreover, Med19 activated the EGFR/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway and exerted its oncogenic activity in an EGFR signaling-mediated manner. In addition, Med19 expression was regulated by miR-101–3p and miR-422a. Med19 expression positively correlated with EGFR expression and negatively correlated with miR-101–3p and miR-422a expression in human breast cancer tissues. Med19 mediated the crosstalk between miR-101–3p/miR-422a and the EGFR/MEK/ERK signaling pathway. This study revealed a new miR-101–3p/miR-422a-Med19-EGFR/MEK/ERK axis that plays a significant role in breast cancer progression. These results help elucidate the potential mechanisms of Med19 in human breast cancer progression.
•Mediator complex subunit 19 (Med19) was elevated in breast cancer and predicted a poor prognosis for breast cancer patients.•Med19 enhanced breast cancer cell proliferation, epithelial–mesenchymal transition, invasion and migration.•Med19 was targeted by microRNA-101–3p/microRNA-422a and exerted oncogenic activity in an EGFR-mediated manner.•Therapeutic inhibition of Med19 expression could hinder breast cancer growth and metastasis.
Abstract
The types and numbers of components in end-of-life (EOL) products are often uncertain during remanufacturing, leading to low disassembly efficiencies for traditional remanufacturing ...disassembly lines. To address this problem, a parallel mixed-flow workstation layout was designed, and a novel parallel mixed remanufacturing disassembly line balancing optimization method for multi-variety products was proposed. A mixed-flow product disassembly task hierarchical assignment matrix was constructed to perform disassembly task allocations for similar components. Furthermore, a parallel mixed-flow remanufacturing disassembly line balancing (PMRDLB) optimization model was developed with the optimization objectives of minimizing the number of workstations, the disassembly line balancing rate, and the remanufacturing value indexes of the components. Furthermore, the multi-objective non-dominated genetic optimization method (NSGA-III) was improved, in which a chromosome construction method, based on the parallel mixed-flow disassembly task allocation matrix, was proposed to conduct mapping between the chromosomes and the PMRDLB model. In addition, non-dominated solution sorting was performed based on a Pareto hierarchy, which increased the searching rate of the algorithm during optimization. Finally, a case study verified the effectiveness and feasibility of the proposed method.
Understanding of prognostic factors and therapeutic targets for breast cancer is imperative for guidance of patient care. We studied 1203 tumour samples from the Gene Expression Omnibus (GEO) to ...evaluate potential genes related to breast cancer. R software was used to analyse differentially expressed long noncoding RNAs (lncRNAs) in the RNA microarray expression profiles GSE45827 and GSE65216 and to identify a series of differentially expressed lncRNAs associated with human breast cancer. Of these lncRNAs, A2M-AS1, a lncRNA that has not been previously reported, was significantly upregulated in human breast cancer tissues compared with adjacent nontumour tissues. Importantly, A2M-AS1 upregulation was significantly associated with ER-negative, HER2-positive, and basal-like breast cancer and with poor recurrence-free survival and metastasis-free survival in breast cancer patients. After validating these results in 96 collected human breast cancer tissues and 64 paired adjacent noncancerous tissues, we further investigated the roles of A2M-AS1 in human ER-negative and basal-like breast cancer cells. The results revealed that A2M-AS1 significantly promotes human breast cancer cell proliferation, invasion, and migration. Additionally, bioinformatics analysis of genes coexpressed with A2M-AS1 in the context of human breast cancer combined with qRT-PCR and Western blot assays revealed that A2M-AS1 exerts regulatory effects on downstream factors in the cell adhesion molecule pathway, including CD2 and SELL. These results imply that A2M-AS1 might be a promising candidate prognostic factor and therapeutic target for breast cancer.
Adriamycin (ADM)‐based regimens are the most effective chemotherapeutic treatments for breast cancer. However, intrinsic and acquired chemoresistance is a major therapeutic problem. Our goal was to ...clarify the role of mediator complex subunit 19 (Med19) in chemotherapy resistance and to elucidate the related molecular mechanisms. In this study, ADM‐resistant human cells (MCF‐7/ADM) and tissues exhibited increased Med19 expression and autophagy levels relative to the corresponding control groups. Additionally, MCF‐7/ADM cells showed changes in two selective markers of autophagy. There was a dose‐dependent increase in the light chain 3 (LC3)‐II/LC3‐I ratio and a decrease in sequestosome 1 (P62/SQSTMl) expression. Furthermore, lentivirus‐mediated Med19 inhibition significantly attenuated the LC3‐II/LC3‐I ratio, autophagy‐related gene 3 (Atg3) and autophagy‐related gene 5 (Atg5) expression, P62 degradation, and red fluorescent protein‐LC3 dot formation after treatment with ADM or rapamycin, an autophagy activator. Furthermore, the antiproliferative effects of ADM, cisplatin (DDP), and taxol (TAX) were significantly enhanced after suppressing Med19 expression. Notably, the effects of Med19 on autophagy were mediated through the high‐mobility group box‐1 (HMGB1) pathway. Our findings suggest that Med19 suppression increased ADM chemosensitivity by downregulating autophagy through the inhibition of HMGB1 signaling in human breast cancer cells. Thus, the regulatory mechanisms of Med19 in autophagy should be investigated to reduce tumor resistance to chemotherapy.
Dietary fiber (DF) improves gastrointestinal health and has important associations with the alleviation of intestinal diseases and metabolic syndrome. However, due to DFs complex characteristics, ...such as solubility, viscosity, and fermentability, the mechanism in these was not consistent. As an herbivore, the goose has a prominent digestive ability to DF.
Therefore, we choose low, medium, and high viscosity DFs (respectively resistant starch-3 RS, inulin INU, and β–glucan GLU) as Magang goose diet treatment for 4 wk, to investigate the effect and potential mechanism of different viscosities DFs on the growth and development process of goose.
In summary, three degrees of viscous DFs could decrease the mechanismic lipid level of geese by promoting acid-producing bacteria and short-chain fatty acid (SCFA) production, therefore, activating AMPK pathway-related genes through the gut-liver axis. High viscous DF has a greater lipid-lowering effect on geese, while medium viscous DF has preferable intestinal mucosal protection.
Malignant hyperthermia (MH), characterized by severe myoclonus, pyrexia, tachycardia, hypertension, elevated muscle enzymes, and hypercapnia, often occurs in patients with congenital deformities or ...genetic disorders. Although the reported incidence rate is as low as 1:5000 to 1:100,000, patients with MH exhibit rapid aggravation and an elevated mortality rate. Thus, MH is associated with substantial perioperative risk. Successful treatment of patients with MH largely depends on early diagnosis and timely effective treatment. This clinical report provides a detailed description of a patient with newly diagnosed MH who developed a rapid rise in body temperature, end-tidal carbon dioxide, and heart rate during maxillary osteotomy. After successful rescue, the patient recovered smoothly during the postoperative period, indicating the importance of intraoperative monitoring, early diagnosis, effective treatment, and postoperative monitoring. This case is expected to serve as a reference for future interventions and healthcare practices in managing other patients with MH.
Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective ...effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and αSMA staining), inflammatory response (IL-1β, IL-6, and TNF-α), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.
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•TBN ameliorates D-galactose-induced muscle aging and improves age-related motor deficits in mice•TBN reduces aged-related muscular fibrosis and atrophy, and inflammatory response•TBN improves age-related mitochondrial impairment and activated the AMPK signaling pathway•TBN suppresses muscle atrophy by modulating NF-κB-Murf1/Atrogin-1 signaling•TBN mitigates muscle aging and age-related motor deficits via AMPK signaling activation
•Primary cervical diffuse large B-cell lymphoma (DLBCL) is a quite rare disease, mostly presenting with vaginal bleeding.•We describe a case of primary cervical DLBCL with increased urinaryfrequency ...and dysuria and a bulky cervical mass.•HPV and SCC tests were normal, and a cervical cytology test revealed atypical squamous cells of undetermined significance.•Obtaining adequate lesions biopsy containing both cervical epithelium and mesenchyme helps to avoid misdiagnosis.•DLBCL of the cervix is a chemotherapy-sensitive tumor, and R-CHOP chemotherapy is effective.
Diffuse large B-cell lymphoma (DLBCL) is a rare disease with a crude annual incidence rate of 3.8 cases per 100,000 people. Besides, primary cervical lymphoma is very rare, accounting for only 0.008% of cervical malignancies. (Sant et al., 2010) Although DLBCL patients often present with abnormal vaginal bleeding, it was not involved in this case. In this article, we present a rare case of primary cervical diffuse large B-cell lymphoma with urinary tract symptoms.
A 71-year-old woman who had been suffering from dysuria for two months came to our hospital. A pelvic examination revealed a 10 cm cervical mass, while HPV and squamous cell carcinoma (SCC) antigen tests were negative. The bulky cervical mass invaded the posterior wall of the uterus, vagina, superior rectum, bladder, and bilateral lower ureters, resulting in dysuria and dilatation of the upper ureter. Histopathological and immunohistochemical examination confirmed DLBCL and PET-CT suggested that it was stage IV. After two cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the large lesions were eliminated. Unfortunately, the patient suffered an untimely death unrelated to her disease before the fourth cycle of R-CHOP could begin.
DLBCL of the cervix is a rare, but potentially curable disease if the diagnosis is made accurately, and doing so requires a high index of suspicion for cervical masses with an atypical presentation in which traditional diagnostic methods are equivocal. Obtaining adequate multilayered lesion biopsies containing both cervical epithelium and mesenchyme helps to avoid misdiagnoses. Histopathological biopsy and immunohistochemistry are the gold standards for diagnosis, and R-CHOP chemotherapy is an effective treatment.
Abstract Astrocytes react to central nervous system (CNS) injury and participate in gliotic responses, imparting negative, as well as positive effects on axonal regeneration. Despite the considerable ...biochemical and morphological changes astrocytes undergo following insult, and the known influence of steroids on glial activation, details surrounding glucocorticoid receptor expression and activity are lacking. Such mechanistic information is essential for advancing and enhancing therapies in the treatment of CNS injuries. Using an in vitro wound-healing assay, we found glucocorticoid receptor β (GRβ), not GRα, is upregulated and acts as a regulator of gliosis after injury. In addition, our results suggest that GRβ interacts with β-catenin and is a necessary component for proliferation and migration in both injured astrocytes and glioma cells. Further analysis indicated GRβ/β-catenin interaction as a key modulator of astrocyte reactivity through sustained Wnt/β-catenin/TCF signaling in its dominant-negative effect on GRα mediated trans-repression by a GSK-3β-independent manner. These findings expand our knowledge of the mechanism of GRβ action in promoting astrocyte proliferation and migration following injury and in glioma. This information furthers our understanding the function of glucocorticoid receptor in CNS injury and disease, as well as in the basic biochemical responses astrocytes undergo in response to injury and glioma pathogenesis.
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