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Our observations suggest ways these viruses have evolved to achieve greater transmissibility in humans.It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.Chronic stress is a major cause of neuropsychiatric conditions such as depression. Stress vulnerability varies individually in mice and humans, measured by behavioral changes. In contrast to affective symptoms, motor retardation as a consequence of stress is not well understood. We repeatedly imaged dendritic spines of the motor cortex in Thy1-GFP M mice before and after chronic social defeat stress. Susceptible and resilient phenotypes were discriminated by symptom load and their motor learning abilities were assessed by a gross and fine motor task. Stress phenotypes presented individual short- and long-term changes in the hypothalamic-pituitary-adrenal axis as well as distinct patterns of altered motor learning. Importantly, stress was generally accompanied by a marked reduction of spine density in the motor cortex and spine dynamics depended on the stress phenotype. We found astrogliosis and altered microglia morphology along with increased microglia-neuron interaction in the motor cortex of susceptible mice. In cerebrospinal fluid, proteomic fingerprints link the behavioral changes and structural alterations in the brain to neurodegenerative disorders and dysregulated synaptic homeostasis. Our work emphasizes the importance of synaptic integrity and the risk of neurodegeneration within depression as a threat to brain health.Circular RNAs (circRNAs) are involved in the pathogenesis of certain renal diseases, however, the function and mechanism of them in renal fibrosis remains largely unknown. In the present study, RNA expression data in unilateral ureteral obstruction (UUO) kidneys was obtained from our previous circRNA Microarray and public Gene Expression Omnibus datasets to construct a ceRNA network. The effects of target circRNA as long as the homologous human circRNA on renal fibrosis was examined in vitro and in vivo. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was further performed among genes regulated by the human circRNA. We found that circRNA_37492, showing well connection degree in the ceRNA network, was abundant expression and high sequence conservation. We observed that the expression of circRNA_37492 was induced by the TGF-β1 or UUO in BUMPT cells and C57BL/6 mice, respectively. In vitro, cytoplasmic circRNA_37492 inhibited type I, III collagen and fibronectin deposition by sponging miR-7682-3p and then upregulated its downstream target Fgb. In vivo, overexpression of circRNA_37492 attenuated fibrotic lesions in the kidneys of UUO mice via targeting miR-7682-3p/Fgb axis. Furthermore, hsa_circ_0012138, homologous with circRNA_37492, may potentially target miR-651-5p/FGB axis in human renal fibrosis. Not only that, GO and KEGG enrichment revealed that hsa_circ_0012138-regulated genes were previously demonstrated to related to the fibrosis. In conclusion, we for the first time demonstrated that circRNA_37492 attenuated renal fibrosis via targeting miR-7682-3p/Fgb axis, and the homologous hsa_circRNA_0012138 was speculated as a possible ceRNA to regulate multiple gene expressions and involve in human renal fibrosis, suggesting that circRNA_37492/hsa_circ_0012138 may serve as potent therapy target for obstructive renal fibrosis disease.Aerobic glycolysis (the Warburg effect) has been demonstrated to facilitate tumor progression by producing lactate, which has important roles as a proinflammatory and immunosuppressive mediator. However, how aerobic glycolysis is directly regulated is largely unknown. Here, we show that ectopic Zeb1 directly increases the transcriptional expression of HK2, PFKP, and PKM2, which are glycolytic rate-determining enzymes, thus promoting the Warburg effect and breast cancer proliferation, migration, and chemoresistance in vitro and in vivo. In addition, Zeb1 exerts its biological effects to induce glycolytic activity in response to hypoxia via the PI3K/Akt/HIF-1α signaling axis, which contributes to fostering an immunosuppressive tumor microenvironment (TME). Mechanistically, breast cancer cells with ectopic Zeb1 expression produce lactate in the acidic tumor milieu to induce the alternatively activated (M2) macrophage phenotype through stimulation of the PKA/CREB signaling pathway. Clinically, the expression of Zeb1 is positively correlated with dysregulation of aerobic glycolysis, accumulation of M2-like tumor-associated macrophages (TAMs) and a poor prognosis in breast cancer patients. In conclusion, these findings identify a Zeb1-dependent mechanism as a driver of breast cancer progression that acts by stimulating tumor-macrophage interplay, which could be a viable therapeutic target for the treatment of advanced human cancers.Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. DL-AP5 molecular weight Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.BACKGROUND Open distal humeral fractures (DHFs) often lead to loss of elbow function, thereby seriously affecting patient quality of life. The aim of this study was to evaluate the treatment outcomes of 2 surgical techniques to determine the better method for repairing open DHFs. Both groups were treated with immediate debridement first, and then group I had only internal fixation (IF), while group II underwent initial external fixation (EF) followed by IF surgery. MATERIAL AND METHODS This retrospective study included 32 patients who had open DHFs between 2013 and 2018. Twelve patients underwent thorough debridement and temporary EF treatment and converted to IF as the ultimate treatment. Twenty patients were treated with immediate open reduction and internal fixation (ORIF). Data of final treatment outcomes were analyzed at the latest follow-up. A comparative analysis of radiological results, function observations, and complications was performed for the 2 surgical groups. RESULTS All DHFs and osteotomized olecranon united after a mean of 5.2±1.21 months. No significant differences were observed in other preoperative demographic data between the 2 groups. Moreover, there was no significant difference in postoperative complications, elbow range of motion, or fracture healing time between the 2 groups. CONCLUSIONS The evidence provided by our study highlights the efficacy of definitive IF in treating open DHFs, which is recommended whenever possible. Furthermore, the combination of EF and ORIF, according to the type of soft tissue damage, may be a promising treatment option with a low revision rate for patients with open DHFs.BACKGROUND This article presents a case involving complications after intentional injection of crushed tablets into the arterial circulation, its diagnosis, and the treatment adopted. The diagnosis process illustrates the potential of techniques based on thermal imaging as tools to assess tissue perfusion. Inadvertent intravenous injection of crushed tablets is more common, but there are few reports on arterial circulation, and no studies were found on the self-injection of crushed morphine tablets, particularly into the radial artery. CASE REPORT A 51-year-old man with alcoholism and a history of illegal drug usage intentionally self-injected 3 crushed morphine tablets into his right radial artery. The patient progressed with compartment syndrome, requiring decompressive fasciotomy of the right forearm and ischemia of the right fingers, which were amputated. He presented with rhabdomyolysis and required dialysis. The patient agreed to full heparinization, corticotherapy, and the use of nitroglycerin and prostaglandin E1. Due to the progression of the necrotic area, the patient underwent proximal phalanx excision and surgical reconstruction of the right-hand remnant. CONCLUSIONS The injection of morphine tablets into circulation caused severe complications, which led to the excision of the proximal phalanx and the surgical reconstruction of the remnant of the right hand. In the present case, infrared thermography proved to be an effective method in assessing tissue perfusion.
To collate existing qualitative research examining patients' medication-taking experiences in secondary prevention of acute myocardial infarction (AMI) and produce new knowledge, a systematic review and meta-synthesis of patient qualitative studies was conducted.
A systematic review found nine reports suitable for inclusion. Themes found by the report authors and report characteristic data were extracted. Reports were assessed for quality. A meta-synthesis using thematic coding and constant comparison method produced higher order themes, and these were used to construct a statement organised by theme using specific examples from the included studies.
All patients discussed their medication-taking in thematic categories of beliefs about medication and illness, personal ability and interpersonal factors. Themes differed between classes of medication and between patients, suggesting tailored interventions to medications and individual patients would be appropriate. Some themes overlapped with those discussed by the broader group of cardiovascular patients, but some themes were unique to this myocardial infarction patient group, again indicating that a tailored approach is appropriate for this patient group.
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