• Karlsson Andrews posted an update 6 months ago

    Circadian clock is important to maintain the physiological functions, as maintenance of immune system. A strategy for imposes rhythmicity in the physiological systems may be adopted of exercise training routine. The lifelong regular practice of physical exercise decelerates the processes of aging, providing better quality and prolongation of life. Thus, in this review, we will focus on how aging affects circadian rhythms and its relationship to inflammatory processes (inflammaging), as well as the role of physical exercise as a regulator of the circadian rhythm, promoting aging with rhythmicity.Diabetic nephropathy (DN) is a chronic complication of diabetes mellitus (DM) with approximately 30-40% of patients with DM developing nephropathy, and it is the leading cause of end-stage renal diseases and diabetic morbidity. The pathogenesis of DN is primarily associated with irregularities in the metabolism of glucose and lipid leading to hyperglycemia-induced oxidative stress, which has been a major target together with blood pressure regulation in the control of DN progression. However, the regulation of 5′ adenosine monophosphate-activated protein kinase (AMPK), a highly conserved protein kinase for maintaining energy balance and cellular growth and repair has been implicated in the development of DM and its complications. Therefore, targeting AMPK pathway has been explored as a therapeutic strategy for the treatment of diabetes and its complication, although most of the mechanisms have not been fully elucidated. In this review, we discuss the structure of AMPK relevant to understanding its allosteric regulation and its role in the pathogenesis and progression of DN. We also identify therapeutic agents that modulate AMPK and its downstream targets with their specific mechanisms of action in the treatment of DN.

    Corneal nerve fibers are derived from the ophthalmic division of the trigeminal ganglion (TG). Here, by sequencing of microRNAs (miRNAs) and messenger RNAs (mRNAs) from diabetic and normal TG tissues, we aimed to uncover potential miRNAs, mRNAs, and the network of their interactions involved in the pathogenesis of diabetic corneal neuropathy.

    We performed RNA sequencing to systematically screen out differentially expressed miRNAs and mRNAs in TG tissues from diabetic and normal mice. Functional enrichment analyses were performed to illustrate the biological functions of differentially expressed mRNAs (DEmRNAs). Following this, miRNA-mRNA regulatory networks were built by means of bioinformatics methods to suggest regulatory role for miRNAs in the pathogenesis of diabetic corneal neuropathy. Finally, the credibility of the sequencing-based results was validated using qRT-PCR.

    Sequencing analyses disclosed that 68 miRNAs and 114 mRNAs were differentially expressed in diabetic TG tissues compared with normal TG samples. The functional analyses showed that DEmRNAs participated in diabetes-related biological processes. After applying an optimized approach to predict miRNA-mRNA pairs, a miRNA-mRNA interacting network was inferred. Subsequently, the expression and correlation of miR-350-5p and Mup20, miR-592-5p and Angptl7 as well as miR-351-5p and Elovl6 were preliminarily validated.

    Our study provides a systematic characterization of miRNA and mRNA expression in the TG during diabetic corneal neuropathy and will contribute to the development of clinical diagnostic and therapeutic strategies for diabetic corneal neuropathy.

    Our study provides a systematic characterization of miRNA and mRNA expression in the TG during diabetic corneal neuropathy and will contribute to the development of clinical diagnostic and therapeutic strategies for diabetic corneal neuropathy.Asthma is a chronic inflammatory and allergic disease that is mainly characterized by reversible airway obstruction and bronchial hyperresponsiveness. The incidence of asthma is increasing with more than 350 million people worldwide are affected. Up to now, there is no therapeutic option for asthma and most of the prescribed drugs aim to ameliorate the symptoms of the disease especially during the acute exacerbations after trigger exposure. Asthma is a heterogonous disease that involves interactions between inflammatory mediators and cellular components within the disease microenvironment including inflammatory and structural cells. Cysteinyl leukotrienes (cys-LTs) are inflammatory lipid mediators that have potent roles in asthma pathogenesis. CysLTs consisting of LTC4, LTD4, and LTE4 are mainly secreted by leukocytes and act through three main G-protein coupled receptors (CysLT1R, CysLT2R, and CysLT3R). LTD4 is the most potent bronchoconstrictor which gives it the priority to be discussed in detail in this review. LTD4 binds with high affinity to CysLT1R and many studies showed that using CysLT1R antagonists such as montelukast has a beneficial effect for asthmatics especially in corticosteroid refractory cases. DNA inhibitor Since asthma is a heterogeneous inflammatory disease of many cell types involved in the disease pathogenies and LTD4 has a special role in inflammation and bronchoconstriction, this review highlights the role of LTD4 on each cellular component in asthma and the benefits of using CysLT1R antagonists in ameliorating LTD4-induced effects.Effective river water quality management and planning is a complex issue challenged by various complexities and uncertainties. A simulation-based interval chance-constrained quadratic programming (ICCQP) model is developed for the seasonal planning of water quality management (WQM) under various uncertainties. The proposed model incorporates interval quadratic programming, chance-constrained programming, and a seasonal water quality simulation model within a general framework for WQM. Uncertainties associated with the objective and the coefficients in the left-hand sides of the constraints are tackled as intervals. Meanwhile, parameter uncertainties on the right-hand sides are characterized using probability distributions. Nonlinearities in the cost function are reflected by quadratic programming. A multi-segment water quality model is used to simulate the dynamic interactions between wastewater discharges and river water quality. The proposed ICCQP-WQM model is applied in a real case study for the control of total phosphorus (TP) in the central Grand River in Ontario, Canada.

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