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Vazquez Ebsen posted an update 2 days, 7 hours ago
Adipocyte account for the largest component in breast tissue. Dysfunctional adipocyte metabolism, such as metaflammation in metabolically abnormal obese patients, will cause hyperplasia and hypertrophy of its constituent adipocytes. Inflamed adipose tissue is one of the biggest risk factors causing breast cancer. Factors linking adipocyte metabolism to breast cancer include dysfunctional secretion of proinflammatory mediators, proangiogenic factors and estrogens. The accumulation of tumor supporting cells and systemic effects, such as insulin resistance, dyslipidemia and oxidative stress, which are caused by abnormal adipocyte metabolism, further contribute to a more aggressive tumor microenvironment and stimulate breast cancer stem cell to influence the development and progression of breast cancer. Here, in this review, we focus on the adipocyte metabolism in regulating breast cancer progression, and discuss the potential targets which can be used for breast cancer therapy. Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic inherited kidney disease characterized by renal progressive fluid-filled cysts and interstitial fibrosis. Inhibiting renal cyst development and interstitial fibrosis has been proven effective in delaying the progression of ADPKD. The purpose of this study was to discover effective drugs from natural products for preventing and treating ADPKD. Candidate compounds were screened from a natural product library by virtual screening. The Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model, and orthologous mouse model of ADPKD were utilized to determine the pharmacological activities of the candidate compounds. Western blot and morphological analysis were used to investigate underlying mechanisms. The experimental results showed that 0.625, 2.5, and 10 μM cardamonin dose-dependently reduced formation and enlargement in MDCK cyst model. Cardamonin also significantly attenuated renal cyst enlargement in ex vivo mouse embryonic kidneys and PKD mouse kidneys. We found that cardamonin inhibited renal cyst development and interstitial fibrosis by downregulating the MAPK, Wnt, mTOR, and transforming growth factor-β/Smad2/3 signaling pathways. Cardamonin significantly inhibits renal cyst development and interstitial fibrosis, suggesting that cardamonin shows promise as a potential therapeutic drug for preventing and treating ADPKD. Early-life exposure to different stressors can lead to various consequences on fish health status in later life development. To evaluate the effects of Aeromonas salmonicida achromogenes infection in the early-life on immunity in adulthood, zebrafish were either early-infected at 18 days post-fertilization (dpf), chronically infected from 18 to 35 dpf, or late infected at 35 dpf and then grown up to 61 dpf to be re-infected with the pathogen. The age of first infection was shown to influence both, level and timing of the immune gene expressions, especially for inflammation-related genes. In addition, evidence for an innate immune memory in zebrafish primarily infected with the pathogen at 35 dpf and re-infected at 61dpf provide new insights to consolidate the concept of a “trained” innate immunity in fish. check details The protein inhibitor of activated STAT (PIAS) proteins are important signal transduction modulator family and regulate the innate immune signaling pathway induced by certain transcription factors, including NF-κB, IRF3, and JAK/STAT. The PIAS protein mechanism that regulates innate immune response in mammals has been well described in the literature; however, whether the PIAS gene exists in ducks as well as the role of PIAS in duck IFN-β expression is still unclear. Here, we cloned duck PIAS (duPIAS), finding PIAS2 could repress IFN-β production. DuPIAS2 contains SAP-PINIT-RLD-S/T characteristic domains, and its overexpression could inhibit virus-induced IFN-β promoter activation. Moreover, duPIAS2 interacts with duck interferon regulatory factor 7 (IRF7) and inhibits IFN-β promoter activation induced by duck IRF7. Additionally, its inhibitory function does not rely on its SUMO E3 ligase activity but rather its C-terminal portion. The above results demonstrate that duPIAS2 is a repressor of IFN-β production induced by duck IRF7. OBJECTIVE The international outbreak of cardiac surgery-associated Mycobacterium chimaera infections was traced back to infectious aerosols originating from contaminated water reservoirs of heater-cooler devices (HCD). In general, nontuberculous mycobacteria (NTM) frequently colonize water systems and can contaminate medical devices. Data on detection of NTM other than M. chimaera in samples gathered from HCDs are scarce. The present study summarizes prospective mycobacterial surveillance of five HCDs over more than four years. METHODS A cohort of five, in 2014 factory-new acquired, LivaNova 3T (London, UK) HCDs were prospectively followed. Until mid-April 2014 HCDs were maintained according to the manufacturer’s recommendations, subsequently according to an intensified in-house protocol including exhaust air evacuation. Mycobacterial surveillance cultures consisted of monthly water samples gathered from patient and cardioplegia circuits, as well as airflow samples. RESULTS Out of 441 water samples, 170 (38.6%) revealed NTM growth. The most frequently detected NTM were Mycobacterium chimaera (n=120 (67.4%)), Mycobacterium gordonae (n=35 (19.7 %)), and Mycobacterium paragordonae (n=17 (9.6%)). Growth of NTM, M. chimaera and M. paragordonae was significantly more common in water samples derived from the patient than the cardioplegia circuit of the HCD. Three (2.0%) out of 150 air samples grew NTM. CONCLUSION Growth of NTM in HCD water samples was frequent. Diverse NTM species were detected, with M. chimaera being most common. The majority of air samples remained negative. The relevance of NTM other than M. chimaera contaminating HCDs is poorly defined, but a recent report on a HCD-associated outbreak with Mycobacterium abscessus confirms a potential threat. BACKGROUND Quality improvement (QI) methods are recommended to address healthcare-associated infections (HAIs) in hospitals, but while internal initiatives have been commonly studied, there is little evidence on the application and effect of a QI approach from an external system-wide perspective. OBJECTIVE To analyze the effect of a national system-wide QI initiative aimed at promoting HAI prevention via regulatory interventions in Brazil. METHOD A QI cycle approach designed and assessed with a before and after quasi-experimental design was implemented by a Brazilian Health Regulatory Agency (ANVISA), targeting 1,869 hospitals. Eleven evidence-based quality indicators related to HAIs prevention and a composite measure were built, shared and assessed; the intervention to improve was then based on participative multifaceted regulatory actions. Absolute and relative improvements were estimated after the intervention. RESULTS 563 hospitals (30.1% response) totaling 86,837 beds participated in the baseline assessment, and 681 hospitals (36.