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Mitochondrial dysfunction is the main cause of gradual deterioration of structure and function of neuronal cells, eventually resulting in neurodegeneration. Studies have revealed a complex interrelationship between neurotoxicant exposure, mitochondrial dysfunction, and neurodegenerative diseases. Alteration in the expression of microRNAs (miRNAs) has also been linked with disruption in mitochondrial homeostasis and bioenergetics. In our recent research (Cellular and Molecular Neurobiology (2023) https://doi.org/10.1007/s10571-023-01362-4), we have identified miR-29b-3p as one of the most significantly up-regulated miRNAs in the blood of Parkinson's patients. The findings of the present study revealed that neurotoxicants of two different natures, that is, arsenic or rotenone, dramatically increased miR-29b-3p expression (18.63-fold and 12.85-fold, respectively) in differentiated dopaminergic SH-SY5Y cells. This dysregulation of miR-29b-3p intricately modulated mitochondrial morphology, induced oxidative stress, and perturbed mitochondrial membrane potential, collectively contributing to the degeneration of dopaminergic cells. Additionally, using assays for mitochondrial bioenergetics in live and differentiated SH-SY5Y cells, a reduction in oxygen consumption rate (OCR), maximal respiration, basal respiration, and non-mitochondrial respiration was observed in cells transfected with mimics of miR-29b-3p. Inhibition of miR-29b-3p by transfecting inhibitor of miR-29b-3p prior to exposure to neurotoxicants significantly restored OCR and other respiration parameters. Furthermore, we observed that induction of miR-29b-3p activates neuronal apoptosis via sirtuin-1(SIRT-1)/YinYang-1(YY-1)/peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)-regulated Bcl-2 interacting protein 3-like-dependent mechanism. Collectively, our studies have shown the role of miR-29b-3p in dysregulation of mitochondrial bioenergetics during degeneration of dopaminergic neurons via regulating SIRT-1/YY-1/PGC-1α axis.
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Background Diabetes mellitus causes microvascular complications in the eyes and kidneys as well as the nervous system, among other parts of the body. Lungs are a potential target organ for diabetic microvascular complications and remain the least researched among diabetic patients. The aim of this study was to explore whether there is any difference in pulmonary functions in patients with diabetes mellitus compared to those without. Methodology A comparative cross-sectional study was conducted on 50 participants each with and without type II diabetes mellitus. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1 as a percentage of FVC in percentage (FEV1%), peak expiratory flow rate in L/second (PEFR), forced expiratory flow rate in L/second in 25% of FVC (FEF25%), forced expiratory flow rate in L/second in 50% of FVC (FEF50%), forced expiratory flow rate in L/second in 75% of FVC (FEF75%), forced expiratory flow rate during 25-75% of expiration (FEF25-75%), and maximal voluntary ventilation (MVV), of both groups were analyzed using the NDD Large True Flow (Easy One) spirometer (NDD Meditechnik AG., Switzerland). A fully automated chemistry analyzer and linear chromatography were used for glycemic control measurements. Results All pulmonary function test parameter values were lower in participants with diabetes mellitus compared to those without, except FEV1% and PEFR, which indicates a mixed pattern of lung dysfunction. FVC had a significant negative correlation with the duration of diabetes (r = -0.299, p = 0.034). Conclusions Type II diabetes mellitus patients had significant dysfunction in pulmonary functions with early involvement of restrictive parameters which can be monitored/diagnosed by regularly following up patients by measuring pulmonary functions, and, hence, can be taken care of.
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BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has negatively impacted respiratory health worldwide. The severity of the disease varies considerably, and patients may present with bronchitis, pneumonia, and acute respiratory distress syndrome. This study aims to quantify the parameters of the pulmonary function test (PFT) with regard to the severity of COVID-19 and understand the pattern of PFT in reference to the status of selected morbidities and body mass index. MATERIALS AND METHODS: This is a hospital-based, comparative, cross-sectional study. A total of 255 COVID-19 survivors underwent clinical assessment, a PFT, and a 6-minute walk test. Participants were divided into mild, moderate, and severe disease groups. The parameters were compared between these groups. The PFT and 6-minute walk tests were conducted using an NDD Digital computerized spirometer (NDD Meditechnik AG., Switzerland) and a fingertip pulse oximeter (Hasely Inc., India), respectively. RESULTS: All PFT parameters showed significant differential distribution among the severity groups (p<0.001) except for forced expiratory volume in 1 s/ forced vital capacity (FEV1/FVC) and forced expiratory flow (FEF) during 25%-75% expiration and peak expiratory flow (PEF). Among severe category participants forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC, were significantly reduced as compared to mild and moderate. Severity was significantly affected by age >50 years. Severe category participants were seen in 31% of normal, 58% of pre-obese, and 53% of obese participants; however, this difference was insignificant. A significant reduction in SPO2 on the 6-minute walk test was observed in severely sick participants. CONCLUSIONS: COVID-19 is associated with a mixed pattern of spirometry. Poor prognosis is associated with older age, obesity, and multimorbidity.
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The immune system is one of the primary targets of airborne particulate matter. Recent evidence suggests that mitochondria lie at the center of particulate matter-induced immunotoxicity. Particulate matter can directly interact with mitochondrial components (proteins, lipids, and nucleic acids) and impairs the vital mitochondrial processes including redox mechanisms, fusion-fission, autophagy, and metabolic pathways. These disturbances impede different mitochondrial functions including ATP production, which acts as an important platform to regulate immunity and inflammatory responses. Moreover, the mitochondrial DNA released into the cytosol or in the extracellular milieu acts as a danger-associated molecular pattern and triggers the signaling pathways, involving cGAS-STING, TLR9, and NLRP3. In the present review, we discuss the emerging role of mitochondria in airborne particulate matter-induced immunotoxicity and its myriad biological consequences in health and disease.