RESUMEN
The repercussions of the early loss of primary teeth, be it from trauma or caries, encompass compromised chewing efficiency, diminished aesthetics, potential development of abnormal oral habits, and difficulty in articulation of labiodental sounds, significantly influencing the child's psychological well-being and behavior. Moreover, the untimely loss of posterior teeth results in the loss of space, potentially leading to malocclusion and functional disruptions. Hence, addressing dental rehabilitation in these cases is both a challenge and a necessity. A toddler aged two and a half was brought to our department with a primary concern of multiple caries. Severe decay with 54, 61, 62, and 64 and missing 51 and 52 were seen. The child experienced pain from decayed back teeth, and the parents were distressed about compromised aesthetics caused by decayed front teeth. Given the child's young age and the sufficient time for permanent teeth to emerge, their concerns were heightened. To address these issues, a modified Groper's appliance was crafted to restore aesthetics and functionality. A supplementary crib-like wire component was incorporated into the appliance to facilitate a simpler and aesthetically pleasing composite crown buildup. Satisfaction with the treatment was evident from both the parents and the child. Subsequent follow-up sessions revealed no adverse effects attributable to the appliance, thus concluding that the additional wire component seamlessly integrated into the appliance offers several advantages, including enhanced aesthetics through composite shade matching for a simplified crown buildup. Particularly in remote areas, where obtaining a set of deciduous acrylic teeth can be challenging, this feature proves to be advantageous. It eliminates the necessity to trim permanent acrylic teeth to achieve a deciduous appearance. Additionally, the time and cost associated with the laboratory fabrication of heat-cure acrylic crowns can be circumvented. This distinctive case report underscores the creation of a modified Groper's appliance for the aesthetic and functional rehabilitation of a child grappling with early childhood caries (ECC). The appliance was well received, and no adverse outcomes were observed.
RESUMEN
Neurogenesis occurs throughout life in the hippocampus of the brain, and many environmental toxicants inhibit neural stem cell (NSC) function and neuronal generation. Bisphenol-A (BPA), an endocrine disrupter used for surface coating of plastic products causes injury in the developing and adult brain; thus, many countries have banned its usage in plastic consumer products. BPA analogs/alternatives such as bisphenol-F (BPF) and bisphenol-S (BPS) may also cause neurotoxicity; however, their effects on neurogenesis are still not known. We studied the effects of BPF and BPS exposure from gestational day 6 to postnatal day 21 on neurogenesis. We found that exposure to non-cytotoxic concentrations of BPF and BPS significantly decreased the number/size of neurospheres, BrdU+ (proliferating NSC marker) and MAP-2+ (neuronal marker) cells and GFAP+ astrocytes in the hippocampus NSC culture, suggesting reduced NSC stemness and self-renewal and neuronal differentiation and increased gliogenesis. These analogs also reduced the number of BrdU/Sox-2+, BrdU/Dcx+, and BrdU/NeuN+ co-labeled cells in the hippocampus of the rat brain, suggesting decreased NSC proliferation and impaired maturation of newborn neurons. BPF and BPS treatment increases BrdU/cleaved caspase-3+ cells and Bax-2 and cleaved caspase protein levels, leading to increased apoptosis in hippocampal NSCs. Transmission electron microscopy studies suggest that BPF and BPS also caused degeneration of neuronal myelin sheath, altered mitochondrial morphology, and reduced number of synapses in the hippocampus leading to altered cognitive functions. These results suggest that BPF and BPS exposure decreased the NSC pool, inhibited neurogenesis, induced apoptosis of NSCs, caused myelin degeneration/synapse degeneration, and impaired learning and memory in rats.
RESUMEN
Increasing evidence of sperm RNA's role in fertilization and embryonic development has provided impetus for its isolation and thorough characterization. Sperm are considered tough-to-lyse cells due to the compact condensed DNA in sperm heads. Lack of consensus among bovine sperm RNA isolation protocols introduces experimental variability in transcriptome studies. Here, we describe an optimized method for total RNA isolation from bovine sperm using the TRIzol reagent. This study critically investigated the effects of various lysis conditions on sperm RNA isolation. Sperm suspended in TRIzol were subjected to a combination of mechanical treatments (sonication and passage through a 30G needle and syringe) and chemical treatments (supplementation with reducing agents 1,4-dithiothreitol and tris(2-carboxyethyl) phosphine hydrochloride (TCEP)). Microscopic evaluation of sperm lysis confirmed preferential sperm tail versus sperm head lysis. Interestingly, only TCEP-supplemented TRIzol (both mechanical treatments) had progressive sperm head lysis and consistently yielded total sperm RNA. Furthermore, RNA integrity was confirmed based on the electrophoresis profile and an absence of genomic DNA and somatic cells (e.g., epithelial cells, spermatids, etc.) with RT-qPCR. Our findings highlighted the importance of sperm lysis, specifically of the sperm head using TCEP with mechanical treatment, in total RNA isolation and presented a bovine-specific sperm RNA isolation method to reduce experimental variabilities.
Asunto(s)
Guanidinas , Fenoles , Fosfinas , Semen , Espermatozoides , Masculino , Animales , Bovinos , Espermatozoides/química , Cabeza del Espermatozoide , ARN/análisis , ADNRESUMEN
Background: Forced vital capacity (FVC) and six-minute walk distance (6MWD) are robust markers in interstitial lung diseases (ILD) to assess severity and prognosis. It is unknown whether high-resolution computed tomography pattern has any independent effect on the exercise capacity in ILD. We compared six-minute walk test (6MWT) parameters between usual interstitial pneumonia (UIP) and non-UIP ILD after adjusting for FVC. Methods: Data from a tertiary care ILD clinic were retrospectively analysed. Based on HRCT, patients were classified as UIP and non-UIP. 6MWT parameters and FVC were recorded for enrolled patients. 6MWD, distance-saturation product (DSP) and exertional desaturation were compared between UIP and non-UIP, using analysis of covariance (ANCOVA), with per cent predicted FVC as covariate. Patients were grouped as mild (≥70%), moderate (51%-69%) and severe (≤50%) based on FVC severity. Results: Out of 169 patients enrolled, only patients with all three data points: spirometry, 6MWT and HRCT were included in the analysis (n = 139). UIP group comprised 56 (40.3%), while non-UIP group had 83 (59.7%) patients. More females and lesser smokers were present in non-UIP group. Mean predicted FVC% was similar between the two HRCT groups (P = 0.611) and had a statistically significant, though very weak to weak correlation with 6MWT parameters {6MWD (r = 0.138); pred 6MWD% (r = 0.170); desaturation (r = -0.227); DSP index (r = 0.166)}. Analysis of covariance showed no statistically significant difference in the 6MWT parameters between UIP and non-UIP groups for similar FVC levels. Conclusion: For a similar level of lung function, exercise capacity was similar for patients with UIP and non-UIP pattern ILD.
RESUMEN
Introduction: Myopia is defined as a refractive error in which rays of light entering the eye parallel to the optic axis are brought to focus in front of the retina when accommodation is relaxed. Globally, myopia prevalence is on the rise for unknown reasons. The aim of the study was to find out the prevalence of myopia among undergraduates of a medical school. Methods: A descriptive cross-sectional study was conducted among medical undergraduates of a medical school between 2 May 2022 to 3 August 2022 after receiving ethical approval from the Institutional Review Committee of the same institute (Reference number: 21/20). A proforma was distributed among the medical undergraduates and data from known myopic students were collected. A convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 279 medical undergraduates, myopia was seen in 119 (42.65%) (36.85-48.45, 95% Confidence Interval). The mean age of the myopic undergraduates was 21±1.47 years. Conclusions: The prevalence of myopia among undergraduates was found to be lower than the other studies done in similar settings. Keywords: medical students; myopia; prevalence.
Asunto(s)
Miopía , Errores de Refracción , Estudiantes de Medicina , Humanos , Adulto Joven , Adulto , Estudios Transversales , Miopía/epidemiología , PrevalenciaRESUMEN
The study compared efficacy of three sperm selection techniques in improving freezability of low-quality Murrah buffalo bull ejaculates. Sephadex (SEP), Sephadex ion-exchange filtration (SIE), and 40/80% BoviPure™ (BP) gradient centrifugation protocols were standardized (ejaculates, n = 24). In Experiment-I, Sephadex G-75, G-100, and combined Sephadex G (75-100) column filtrates were compared. In Experiment-II, BP protocols: 200 g-10 min, 250 g-5, and 10 min, 300 g-10, and 15 min were compared. In fresh semen, Sephadex G (75-100) filtration and 250 g-5 min BP protocol improved sperm functions and were used in Experiment-III, where SEP G (75-100), SIE G (75-100), and 250 g-5 min BP processed ejaculates (n = 48) were cryopreserved and compared at post-thaw stage. The mean recovery rate differed in order: SEP > SIE > BP. SIE filtration significantly improved progressive motility, livability, membrane integrity, bovine cervical mucus penetration and live non-apoptotic sperm. Compared with control, all three techniques equally reduced post-dilution and post-thaw lipid peroxidation (LPO) rate. SEP post-thaw filtrates observed lower cryocapacitation-like changes, LPO (C11-BODIPY581/591), and higher active mitochondria than other treatments. SIE and SEP equally improved post-thaw acrosome-intact sperm over BP. Filtration techniques, preferably, Sephadex ion-exchange filtration can most efficiently process low-quality buffalo bull ejaculates for cryopreservation and improve freezability.
Asunto(s)
Preservación de Semen , Semen , Animales , Masculino , Bovinos , Búfalos , Motilidad Espermática , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides , Centrifugación/veterinaria , Criopreservación/veterinaria , Criopreservación/métodos , CrioprotectoresRESUMEN
The effect of carbon doping contents on the microstructure, hardness, and corrosion properties of heat-treated AISI steel grades of plain carbon steel was investigated in this study. Various microstructures including coarse ferrite-pearlite, fine ferrite-pearlite, martensite, and bainite were developed by different heat treatments i.e. annealing, normalizing, quenching, and austempering, respectively. The developed microstructures, micro-hardness, and corrosion properties were investigated by a light optical microscope, scanning electron microscope, electromechanical (Vickers Hardness tester), and electrochemical (Gamry Potentiostat) equipment, respectively. The highest corrosion rates were observed in bainitic microstructures (2.68-12.12 mpy), whereas the lowest were found in the fine ferritic-pearlitic microstructures (1.57-6.36 mpy). A direct correlation has been observed between carbon concentration and corrosion rate, i.e. carbon content resulted in an increase in corrosion rate (2.37 mpy for AISI 1020 to 9.67 mpy for AISI 1050 in annealed condition).
RESUMEN
Background: The current COVID-19 pandemic is an ongoing global healthcare challenge that has caused morbidity and mortality at unprecedented levels. Since the post-COVID pulmonary complications are evolving and challenging, a study was carried out to assess pulmonary cavitation in follow-up COVID cases from an etiological perspective. The aim of this study was to assess the incidence of pulmonary cavitation and describe its etiology and evolution in moderate and severe post-COVID pneumonia patients. Methods: A prospective observational study of all patients admitted to our institution with moderate or severe COVID pneumonia was carried out. Some of these patients again became symptomatic after discharge and developed pulmonary cavitation on imaging. Results: 6.2% (n = 37) out of 589 patients admitted to our institution with moderate or severe COVID pneumonia developed pulmonary cavitation on follow-up. We describe the imaging characteristics of post-COVID cavitation and present these patients' clinical, laboratory, and microbiological parameters. Conclusion: Cavitary lung disease in patients with moderate to severe COVID-19 disease is not uncommon, and an etiological workup is necessary to institute timely and correct therapy.
RESUMEN
An advanced understanding of sperm function is relevant for evidence-based male fertility prediction and addressing male infertility. A standard breeding soundness evaluation (BSE) merely identifies gross abnormalities in bulls, whereas selection based on single nucleotide polymorphisms and genomic estimated breeding values overlooks sub-microscopic differences in sperm. Molecular tools are important for validating genomic selection and advancing knowledge on the regulation of male fertility at an interdisciplinary level. Therefore, research in this field is now focused on developing a combination of in vitro sperm function tests and identifying biomarkers such as sperm proteins with critical roles in fertility. The Na+-K+ ATPase is a ubiquitous transmembrane protein and its α4 isoform (ATP1A4) is exclusively expressed in germ cells and sperm. Furthermore, ATP1A4 is essential for male fertility, as it interacts with signaling molecules in both raft and non-raft fractions of the sperm plasma membrane to regulate capacitation-associated signaling, hyperactivation, sperm-oocyte interactions, and activation. Interestingly, ATP1A4 activity and expression increase during capacitation, challenging the widely accepted dogma of sperm translational quiescence. This review discusses the literature on the role of ATP1A4 during capacitation and fertilization events and its prospective use in improving male fertility prediction.
Asunto(s)
ATPasa Intercambiadora de Sodio-Potasio , Testículo , Animales , Bovinos , Fertilidad/genética , Masculino , Isoformas de Proteínas/metabolismo , Semen/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Motilidad Espermática , Espermatozoides/metabolismo , Testículo/metabolismoRESUMEN
The use of Pipelines for long-distance transportation of crude oil, natural gas and similar applications is increasing and has pivotal importance in recent times. High specific strength plays a crucial role in improving transport efficiency through increased pressure and improved laying efficiency through reduced diameter and weight of line pipes. TRIP-based high-strength and high-ductility alloys comprise a mixture of ferrite, bainite, and retained austenite that provide excellent mechanical properties such as dimensional stability, fatigue strength, and impact toughness. This study performs microstructure analysis using both Nital etching and LePera etching methods. At the time of Nital etching, it is difficult to distinctly observe second phase. However, using LePera etching conditions it is possible to distinctly measure the M/A phase and ferrite matrix. The fraction measurement was done using OM and SEM images which give similar results for the average volume fraction of the phases. Although it is possible to distinguish the M/A phase from the SEM image of the sample subjected to LePera etching. However, using Nital etching is nearly impossible. Nital etching is good at specific phase analysis than LePera etching when using SEM images.
Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Vasculitis Leucocitoclástica Cutánea , Eritema , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
The regulatory network of mitochondrial biogenesis and dynamics is vital for mitochondrial functions and cellular homeostasis. Any impairment in the mitochondrial network leads to neurodegenerative disorders. Our earlier studies suggest that environmental toxicant Bisphenol-A (BPA) exposure reduces neurogenesis by abnormal mitochondrial dynamics and mitochondrial biogenesis through impairment of mitochondrial fission factor dynamin-related protein (DRP1) and mitochondrial import protein GFER, which leads to demyelination, neurodegeneration, and cognitive deficits in the rats. In the present study, we found that chronic BPA exposure reduces PGC-1α levels (master regulator of mitochondrial biogenesis), alters mitochondrial localization of DRP1 and GFER, and reduces the number of PGC-1α/NeuN+ and PGC-1α/ß-tubulin+ neurons in the rat hippocampus, suggesting reduced PGC-1α-mediated neurogenesis. Nicotinamide significantly increased PGC-1α protein levels, PGC-1α/NeuN+ co-labeled cells in BPA-treated rat hippocampus and PGC-1α/ß-tubulin+ co-labeled cells in neuron culture derived from hippocampal neural stem cells. Interestingly, PGC-1α upregulation by nicotinamide also resulted in increased GFER levels and restored mitochondrial localization of GFER (increased GFER/TOMM20 co-labeled cells) in vitro and in vivo following BPA treatment. Nicotinamide also reduced DRP1 levels and prevented DRP1 mitochondrial localization in BPA-treated neuronal cultures and hippocampus, suggesting reduced mitochondrial fission. This resulted in reduced cytochrome c levels in neuronal culture and reduced hippocampal neurodegeneration (reduced caspase-3/NeuN+ co-labeled neurons) following nicotinamide treatment in BPA-treated group. Consequently, activation of PGC-1α by nicotinamide restored BPA-mediated cognitive deficits in rats. Results suggest that the treatment of nicotinamide has therapeutic potential and rescues BPA-mediated neuronal death and cognitive deficits by upregulating the PGC-1α and GFER-DRP1 link, thus balancing mitochondrial homeostasis.
Asunto(s)
Compuestos de Bencidrilo/farmacología , Niacinamida , Fenoles/farmacología , Tubulina (Proteína) , Animales , Cognición , Dinaminas/metabolismo , Hipocampo/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Proteínas/metabolismo , Ratas , Tubulina (Proteína)/metabolismo , Regulación hacia ArribaRESUMEN
Iodine is anessential micronutrient that plays a crucial role in male reproduction (sexual behavior and semen production performance) by modulating thyroid function and the antioxidant status of the animal. Nonetheless, in Bos indicus bulls, a thorough evaluation of the effects of dietary iodine supplementation on antioxidant status, seminal quality parameters, and its interaction with other minerals is not documented. Twelve Bos indicus (Sahiwal) bulls were distributed into three groups (n = 4 in each group) viz. T1 (control), T2, and T3 and fed diets containing 0.250, 0.375, and 0.500 ppm iodine/ kg dry matter intake, corresponding to 0%, 50%, and 100% higher than ICAR (2013) recommendations, respectively. The experimental feeding was carried out for 60 days and the effects on nutrient utilization, hormonal and antioxidant status, and sperm function tests were investigated. Results revealed that body weight, dry matter intake, and nutrient digestibility remained unaffected by dietary supplementation of iodine. Testosterone and thyroxine hormone concentrations were improved (p<0.05) in T2 and T3 groups. Blood and seminal iodine content were also higher (p<0.05) in both the supplemented groups (T2 and T3). Sperm functions viz. viability, physical membrane integrity, acrosomal integrity, motility, and mitochondrial membrane potential were improved (p<0.05) due to iodine supplementation. Furthermore, lipid peroxidation and membrane scrambling in spermatozoa were reduced (p<0.05) in T2 and T3 groups. Blood antioxidant status (total antioxidant activity and GPx levels) was improved (p<0.05) in T2 and T3. Sexual behavior was also improved (p<0.05) in iodine-supplemented groups. Hence, it can be concluded that iodine supplementation at the dose rate of 0.500 ppm in the Bos indicus bull diet is beneficial in improving hormonal status, antioxidant status, and semen quality.
Asunto(s)
Yodo , Semen , Animales , Antioxidantes/farmacología , Bovinos , Suplementos Dietéticos , Yodo/farmacología , Complejo Hierro-Dextran/farmacología , Masculino , Micronutrientes , Minerales/farmacología , Análisis de Semen , Motilidad Espermática , Espermatozoides , Testosterona , TiroxinaRESUMEN
A convenient and metal-free synthesis of vinyloxyimidazopyridine derivatives has been attained via BF3.OEt2 promoted one-pot multicomponent approach. This procedure involves a facile coupling of 2-aminopyridine derivatives with arylglyoxal and alkyne derivatives. BF3.OEt2 complexation has successfully catalyzed the reaction at room temperature. Utilization of transition metal-free catalyst, mild reaction conditions, easy handling and operational simplicity are key features of developed process.
Asunto(s)
Piridinas , CatálisisRESUMEN
Mitochondria are vital organelles with a multifaceted role in cellular bioenergetics, biosynthesis, signaling and calcium homeostasis. During oxidative phosphorylation, sperm mitochondria generate reactive oxygen species (ROS) at physiological levels mediating signaling pathways essential for sperm fertilizing competence. Moreover, sperm subpopulation with active mitochondria is positively associated with sperm motility, chromatin and plasma membrane integrity, and normal morphology. However, the osmotic and thermal stress, and intracellular ice crystal formation generate excess ROS to cause mitochondrial dysfunction, potentiating cryoprotectant-induced calcium overload in the mitochondrial matrix. It further stimulates the opening of mitochondrial permeability transition pores (mPTP) to release pro-apoptotic factors from mitochondria and initiate apoptotic cascade, with a decrease in Mitochondrial Membrane Potential (MMP) and altered sperm functions. To improve the male reproductive potential, it is essential to address challenges in semen cryopreservation, precisely the deleterious effects of oxidative stress on sperm quality. During semen cryopreservation, the supplementation of extended semen with conventional antioxidants is extensively reported. However, the outcomes of supplementation to improve semen quality are inconclusive across different species, which is chiefly attributed to the unknown bioavailability of antioxidants at the primary site of ROS generation, i.e., mitochondria. Increasing evidence suggests that the targeted delivery of antioxidants to sperm mitochondria is superior in mitigating oxidative stress and improving semen freezability than conventional antioxidants. Therefore, the present review comprehensively describes mitochondrial-targeted antioxidants, their mechanism of action and effects of supplementation on improving semen cryopreservation efficiency in different species. Moreover, it also discusses the significance of active mitochondria in determining sperm fertilizing competence, cryopreservation-induced oxidative stress and mitochondrial dysfunction, and its implications on sperm fertility. The potential of mitochondrial-targeted antioxidants to modulate mitochondrial functions and improve semen quality has been reviewed extensively.
Asunto(s)
Antioxidantes , Preservación de Semen , Animales , Antioxidantes/farmacología , Criopreservación/veterinaria , Masculino , Mitocondrias , Estrés Oxidativo , Análisis de Semen/veterinaria , Preservación de Semen/veterinaria , Motilidad Espermática , EspermatozoidesRESUMEN
INTRODUCTION: Although appropriate self-medication can ease minor illness and is time and costeffective, it can lead to irrational drug use and increased resistance, leading to prolonged morbidity. Inclined towards medical information and drug indices, medical students have an open arena for self-medication practice. This study was conducted to find the prevalence of self-medication among first and seventh semester medical and dental students in a tertiary care hospital. METHODS: A descriptive cross-sectional study was conducted among medical and dental undergraduates from July 2020 to August 2020 after receiving ethical clearance from the Institutional Review Committee of Kathmandu University School of Medical Sciences (IRC Approval Number:35/20). A questionnaire was responded to by participants through a google form. Participants were enrolled through the convenience sampling method. Data were collected and entered in Microsoft Excel and analyzed using Statistical Package for Social Sciences version 25. RESULTS: Out of 199 respondents, the prevalence of self-medication was 100 (50.3%) (46.76-53.84 at 95% Confidence Interval). First semester medical 36 (73.5%) and dental undergraduates 24 (80%) had higher practice. Seventh-semester medical students 14 (51.9%) usually self-medicated within one day of onset of symptoms. Headache 47 (47%) was the most common indication. Analgesics 62 (62%) were most commonly used drugs procured most commonly from pharmacies 114 (57.3%). Dosage form was drug selection criteria for 120 (60.3%) students. CONCLUSIONS: Since self-medication is crammed with serious health hazards, proper exposure to the topic should be given to medical, dental students, and pharmacists. The implication of selfmedication into the pharmacology syllabus is a must.
Asunto(s)
Estudiantes de Medicina , Estudios Transversales , Hospitales de Enseñanza , Humanos , Nepal , Atención Terciaria de SaludRESUMEN
INTRODUCTION: To establish appropriate health care services in developing countries, rationalization of drug use holds utmost importance. Drug use patterns can be found out using Core Indicators of the World Health Organisation in collaboration with the International Network of Rational Use of Drugs. With the help of the indicators, this study aimed to find out the way the drugs were prescribed in the Medicine out-patient department of a tertiary care hospital. METHODS: A descriptive cross-sectional survey was conducted from October 2019 to March 2020 in a tertiary care hospital. The ethical approval was taken from the Institutional Review Committee of the Dhulikhel hospital (reference number 198/19). Convenient sampling was done. After taking consent from the patient, data was collected from prescriptions written on the patient's card. The data were analysed using Statistical Package for the Social Sciences Version 25. Descriptive statistics were applied and the results were expressed as frequency and percentage, mean and standard deviation. RESULTS: A total of 559 prescriptions were analysed, of which a total of 1427 medicines were found to be prescribed with an average number of medicines per the prescription of 2.55±1.388. Drugs prescribed by generic name were 820 (57.5%), antibiotics were 138 (9.7%) and injections were 8 (0.6%). Drugs prescribed from the Essential Drug List of Nepal was 939 (65.8%). CONCLUSIONS: Our study revealed that despite some results being up to the mark, there is a requisite for the proper regulation of prescribing and dispensing drugs in order to promote rationalisation.
Asunto(s)
Medicamentos Esenciales , Pautas de la Práctica en Medicina , Estudios Transversales , Prescripciones de Medicamentos , Humanos , Centros de Atención Terciaria , Organización Mundial de la SaludRESUMEN
Mitochondrial biogenesis relies on different protein import machinery, as mitochondrial proteins are imported from the cytosol. The mitochondrial intermembrane space assembly (MIA) pathway consists of GFER/ALR and CHCHD4/Mia40, responsible for importing proteins and their oxidative folding inside the mitochondria. The MIA pathway plays an essential role in complex IV (COX IV) biogenesis via importing copper chaperone COX17, associated with the respiratory chain. BPA, an environmental toxicant, found in consumable plastics, causes neurotoxicity via impairment in mitochondrial dynamics, neurogenesis, and cognitive functions. We studied the levels of key regulatory proteins of mitochondrial import pathways and mitochondrial biogenesis after BPA exposure in the rat hippocampus. BPA caused a significant reduction in the levels of mitochondrial biogenesis proteins (PGC1α, and TFAM) and mitochondrial import protein (GFER). Immunohistochemical analysis showed reduced co-localization of NeuN with GFER, PGC-1α, and TFAM suggesting impaired mitochondrial biogenesis and protein import. BPA exposure resulted in damaged mitochondria with distorted cristae in neurons and caused a significant reduction in GFER localization inside IMS as depicted by immunogold electron microscopy. The reduced levels of GFER resulted in defective COX17 import. The translocation of cytochrome c into the cytosol and increased cleaved caspase-3 levels triggered apoptosis due to BPA toxicity. Overall, our study implicates GFER as a potential target for impaired mitochondrial protein machinery, biogenesis, and apoptosis against BPA neurotoxicity in the rat hippocampus.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Hipocampo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Proteínas Mitocondriales/antagonistas & inhibidores , Biogénesis de Organelos , Fenoles/toxicidad , Proteínas/antagonistas & inhibidores , Contaminantes Ocupacionales del Aire/química , Contaminantes Ocupacionales del Aire/metabolismo , Contaminantes Ocupacionales del Aire/toxicidad , Animales , Compuestos de Bencidrilo/química , Compuestos de Bencidrilo/metabolismo , Simulación por Computador , Hipocampo/metabolismo , Hipocampo/ultraestructura , Masculino , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/ultraestructura , Fenoles/química , Fenoles/metabolismo , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/fisiología , Proteínas/metabolismo , Ratas , Ratas WistarRESUMEN
A visible-light-mediated, mild and one-pot three-component reaction in the presence of organophotoredox catalyst Eosin Y using EtOH:H2O as reaction medium for the synthesis of 3-functionalized indole derivatives was developed. Visible light used in the protocol is green, inexpensive, readily available energy source. The sustainable reagents make the protocol compatible with green chemistry demands.