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Ficus benghalensis L. (FB) is a popular plant described in the Indian system of medicine. Traditionally, it is indicated in the treatment of diseases like diabetes mellitus, dysentery, leucorrhoea, menorrhagia, skin disease, rheumatism, inflammatory diseases, blood disorders. This paper accentuates the anti-thrombotic action of FB based on the properties like anti-coagulant, platelet-antiaggregatory, anti-atherogenic hypotensive, hypolipidemic, anti-oxidant, anti-inflammatory and immunomodulatory. All the available data pertaining to FB has been searched in the scientific databases, including PubMed, Google Scholar, ScienceDirect and Scopus. FB is a rich lode of organic compounds such as phenols, flavonoids, alkaloids, tannins, terpenoids and steroids. The various studies show that these phytochemical constituents exhibit wide range of anti-thrombotic actions such as anticoagulant, platelet anti-aggregatory, anti-atherogenic, hypolipidemic, hypotensive, anti-inflammatory, and antioxidant. Various studies (in vitro and in vivo) confirm the potential anti-thrombotic benefit of FB due to the presence of chemical structures that have proven to be effective in thromboembolic conditions. These evidences may benefit in new drug development to treat varied thromboembolic conditions which will not only be cost effective but may allay the fear of side effects.
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Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant-antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.
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Abatacept , Modelos Animales de Enfermedad , Inflamación , Infarto del Miocardio , Animales , Ratas , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Masculino , Inflamación/tratamiento farmacológico , Inflamación/patología , Abatacept/farmacología , Abatacept/uso terapéutico , Ratas Wistar , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patologíaRESUMEN
OBJECTIVES: Flavonoids are polyphenolic compounds found in a wide range of foods, including fruits, vegetables, tea plants, and other natural products. They have been mainly classified as flavanols, flavonols, flavones, isoflavones, flavanones, and flavanonols. In this comprehensive review, we will discuss preclinical pieces of evidence on the potential of flavonoids for the prevention/treatment of myocardial ischemia-reperfusion (IR) injury. KEY FINDINGS: In-vitro and in-vivo studies have shown that flavonoids play an important role in preventing ischemic heart disease (IHD). They possess strong anti-oxidant, anti-inflammatory, anti-bacterial, anti-thrombotic, anti-apoptotic, and anti-carcinogenic activities. In addition, at a molecular level, flavonoids also modulate various pathways like MAPK, NFκB etc. to confer beneficial effects. SUMMARY: The current review of flavonoids in myocardial ischemia-reperfusion injury furnishes updated information that could drive future research. The in-vitro and in-vivo experiments have demonstrated various favourable pharmacological properties of flavonoids. This review provides valuable information to conduct clinical studies, validating the safety aspects of flavonoids in the clinical domain.
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Flavonoides , Daño por Reperfusión Miocárdica , Humanos , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/fisiopatología , Flavonoides/farmacología , Animales , Transducción de Señal/efectos de los fármacos , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Miocardio/metabolismo , Miocardio/patología , Apoptosis/efectos de los fármacos , Fármacos Cardiovasculares/farmacología , Fármacos Cardiovasculares/uso terapéuticoRESUMEN
Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.
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COVID-19 , Insuficiencia Cardíaca , Miocarditis , Infección por el Virus Zika , Virus Zika , Humanos , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Miocarditis/etiologíaRESUMEN
BACKGROUND: Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects. PURPOSE: Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium. STUDY DESIGN: This study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 µg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups. METHODS: On the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin. RESULTS: Arglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose. CONCLUSION: Arglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.
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Lesiones Cardíacas , Infarto del Miocardio , Sesquiterpenos de Guayano , Ratas , Animales , Inflamasomas/metabolismo , Isoproterenol/farmacología , Corazón , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Estrés Oxidativo , Lesiones Cardíacas/metabolismoRESUMEN
BACKGROUND: High blood glucose levels in diabetes lead to vascular inflammation which accelerates atherosclerosis. Herein, Morin was orally administered in male Wistar rats, at the dose of 40 mg/kg for 28 days, and on the 27th and 28th day, ISO was administered to designate groups at the dose of 85 mg/kg s.c., to induce myocardial infarction. RESULTS: Free radical generation, including ROS, in diabetes following ISO administration, leads to the activation of both intrinsic and extrinsic pathways of apoptosis. Morin significantly (p ≤ 0.05) reduced oxidative stress (GSH, MDA, SOD), cardiac injury markers (CK-MB, LDH), inflammation (TNF, IL-6), and apoptosis (Bax, BCl2, Caspase-3). In addition, it also reduced insulin and blood glucose levels. Akt/eNOS, Nrf2/HO-1, MAPK signaling pathways, and Insulin signal transduction pathways were positively modulated by morin pre-treatment. CONCLUSIONS: Morin attenuated oxidative stress and inflammation and also modified the activity of various molecular pathways to mitigate cardiomyocyte damage during ISO-induced MI in diabetic rats.
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BACKGROUND: Diabetes mellitus (DM) is characterized by elevated blood glucose levels either due to insufficient insulin production, defective insulin action, or both. It affects nearly 537 million individuals worldwide. Pharmacological treatment involves the use of oral antidiabetic agents as mono or combination therapy that effectively aids in controlling hyperglycemia. Despite providing therapeutic benefits, these medications limit their use owing to adverse side effects. Certain natural products, including essential oils, have promising anti-diabetic properties. OBJECTIVE: The present study explores the effectiveness of two polyherbal oils and their compound towards the treatment of DM based on an In-silico approach to drug investigations. METHODS: Compounds present in the polyherbal oil formulation were identified using GCMS/MS analysis. Selected compounds undergo molecular docking with the receptor, and proteins play an important role in DM. The potential compounds showing higher interactions than the known inhibitors or inducers were evaluated using molecular dynamic simulations RMSD values. RESULTS: The compounds identified through GC-MS analysis possess anti-diabetic and antiinflammatory properties. With the aid of in silico prediction methods, compounds such as geraniol, cinnamaldehyde, anethole, caryophyllene, terpinyl acetate, cymene, linalool, menthol, Phenol,2-methoxy-3-(2-propenyl), and 2,6- octadienal,3,7-dimethyl were identified as strong binders of GLUT4 and insulin receptor proteins. Geraniol and Phenol,2-methoxy-3-(2-propenyl) interaction with GLUT4 were of particular importance owing to their conformational stability. CONCLUSION: Our data suggest an agonistic effect of compounds on target proteins aiding in enhanced insulin activity and could serve as a potential anti-diabetic agent.
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Sesamol, a lignan obtained from roasted seeds of Sesamum indicum, has high antioxidant and anti-inflammatory activity. In this study, we have investigated the effect of sesamol on Bleomycin (BLM) induced pulmonary toxicity as well as fibrosis in Wistar rats. Lung toxicity was induced by administration of BLM, 0.015 U/g ip, twice weekly for 28 days whereas lung fibrosis was induced by BLM, 0.015 U/g ip, every 5th day for 49 days. Sesamol administration was started 7 days before first dose of BLM in both the models. It was observed that sesamol 50 mg/kg most effectively attenuated pulmonary toxicity by reducing oxidative stress, inflammation and apoptosis. This dose was further evaluated for its anti-fibrotic effect. It was observed that there was a significant reduction in fibrosis. Lung collagen content was markedly reduced. Furthermore, expression of pro-fibrotic proteins, TGF-ß/SMAD and α-SMA, was reduced and that of anti-fibrotic protein, AMPK, was markedly increased. Even though the combination of sesamol with pirfenidone exhibited no additional protection than either drug alone, it is evident from our study that our test drug, sesamol is comparable in efficacy to pirfenidone. Thus, sesamol has promising therapeutic potential in treatment of pulmonary toxicity and fibrosis.
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Bleomicina , Fibrosis Pulmonar , Ratas , Animales , Bleomicina/toxicidad , Ratas Wistar , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/prevención & control , Pulmón/metabolismo , FibrosisRESUMEN
Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-ß (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- ß significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Deficiencia de Vitamina D , Ratas , Humanos , Animales , Hipertensión Arterial Pulmonar/metabolismo , Monocrotalina/toxicidad , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Ratas Sprague-Dawley , Vitamina D/farmacología , Vitamina D/metabolismo , Calcitriol/farmacología , Transducción de Señal , Arteria Pulmonar , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Vitaminas/farmacología , Vitaminas/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Currently, there are no FDA approved antiviral drugs available to treat COVID-19 patients. Also, due to emergence of new SARS-CoV-2 variants, the protective efficacy of vaccines could be reduced, hence it is urgent to have alternative treatments for combating the SARS-CoV-2 infection. Since, there is a long-standing history of herbal medicine in the treatment of respiratory diseases. In the present study, we investigated two polyherbal oil blend viz. Sudarshan AV and Elixir AV (SAV and EAV) in inhibiting SARS-COV-2. From GC-MS analysis of polyherbal oils (SAV and EAV) a total of 11 active compounds were selected, on the basis of their abundance and activity. Further, from the molecular docking studies, we found an inhibitory effect of these compounds on viral envelope and membrane, spike proteins whilst an agonistic effect with human host receptor angiotensin-converting enzyme 2 (ACE2) implicating the crucial role of the individual compound in resistance of SARS-CoV-2. Since, the in-silico results suggest that polyherbal oil (SAV and EAV) contributes in preventing the entry of SARS-CoV-2 into the human body, we further investigated the efficacy of polyherbal formulated essential oil (FEO; SAV & EAV) in prevention and treatment of COVID-19 in hamster model. The male golden Syrian hamsters (n = 23) were divided into 5 groups i.e., Group 1: Control (n = 3); Group 2: Infected (n = 5); Group 3: Infected + Remdesivir (n = 5); Group 4: Infected + FEO (n = 5) and Group 5: Prophylactic FEO + Infected (n = 5). In both treatment and prophylactic groups, the FEO's significantly reduced the lung injury investigated histo-pathologically and viral load expression measured by real time PCR in comparison to infected hamsters. Furthermore, cytokines expression analysis clearly highlighted the efficacy of FEO's due to its anti-inflammatory activity and overall protection in treatment groups. In conclusion, the FEO (SAV & EAV) seem to be potent in both prevention and treatment of COVID-19 and related lung injury.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Lesión Pulmonar , Aceites Volátiles , Enzima Convertidora de Angiotensina 2 , Animales , Antiinflamatorios , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/prevención & control , Cricetinae , Citocinas , Humanos , Lesión Pulmonar/tratamiento farmacológico , Masculino , Simulación del Acoplamiento Molecular , Peptidil-Dipeptidasa A , SARS-CoV-2 , Glicoproteína de la Espiga del CoronavirusRESUMEN
Cardiac hypertrophy is the enlargement of cardiomyocytes in response to persistent release of catecholamine which further leads to cardiac fibrosis. Chrysin, flavonoid from honey, is well known for its multifarious properties like antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic. To investigate the cardioprotective potential of chrysin against isoproterenol (ISO), cardiac hypertrophy and fibrosis are induced in rats. Acclimatised male albino Wistar rats were divided into seven groups (n 6): normal (carboxymethyl cellulose at 0·5 % p.o.; as vehicle), hypertrophy control (ISO 3 mg/kg, s.c.), CHY15 + H, CHY30 + H & CHY60 + H (chrysin; p.o.15, 30 and 60 mg/kg respectively + ISO at 3 mg/kg, s.c.), CHY60 (chrysin 60 mg/kg in per se) and LST + H (losartan 10 mg/kg p.o. + ISO 3 mg/kg, s.c.) were treated for 28 d. After the dosing schedule on day 29, haemodynamic parameters were recorded, after that blood and heart were excised for biochemical, histological, ultra-structural and molecular evaluations. ISO administration significantly increases heart weight:body weight ratio, pro-oxidants, inflammatory and cardiac injury markers. Further, histopathological, ultra-structural and molecular studies confirmed deteriorative changes due to ISO administration. Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways. Data demonstrated that chrysin attenuated myocardial hypertrophy and prevented fibrosis via activation of transforming growth factor-beta (TGF-ß)/Smad signalling pathway.
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Azilsartan is found to be more potent than other angiotensin receptor blockers in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR-γ revealed azilsartan as an agonist of PPAR-γ and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia-reperfusion injury by comparing their antioxidant, ant apoptotic, anti-inflammatory, mitogen-activated protein kinase (MAPK)-modulating ability, and PPAR-γ agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2 ml/kg) telmisartan (10 mg/kg p.o.), azilsartan (10 mg/kg p.o.) or azilsartan with specific PPAR-γ blocker, GW 9662 for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4',6-diamidino-2-phenylindole/terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. An increment in pro-survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR-γ antagonist, GW9662. However, we found that azilsartan upregulated PPAR-γ to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction.
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Bencimidazoles/farmacología , Cardiotónicos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Daño por Reperfusión Miocárdica , Miocardio , Oxadiazoles/farmacología , Telmisartán/farmacología , Animales , Modelos Animales de Enfermedad , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Miocardio/patología , Ratas , Ratas WistarRESUMEN
The role of Saxagliptin in diabetes-associated cardiovascular complications is controversial. This study aimed to investigate whether Saxagliptin could prevent Isoproterenol-induced myocardial changes in diabetic rats and to identify the possible mechanism as well. The high-fat diet/low-dose Streptozotocin-induced type 2 diabetic rats were divided into 3 groups: the control group (0.25% CMC for 28 days), the Isoproterenol group (85 mg/kg Isoproterenol for the last 2 days plus 0.25% CMC for 28 days), and the treatment group (10 mg/kg Saxagliptin for 28 days plus 85 mg/kg Isoproterenol for the last 2 days). Hemodynamic measurements were performed, and samples were examined for RAGE and NF-κB expressions, histopathological and ultrastructural changes, AGEs level, myocardial injury markers, oxidative stress, and apoptosis. Saxagliptin significantly recovered cardiac function (p < .001), reverted myocardial injury and oxidative stress levels back to the control value (p < .05 to p < .001). Saxagliptin alleviates Isoproterenol-induced myocardial injury in diabetic rats by suppressing AGE-RAGE pathway.
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Adamantano/análogos & derivados , Complicaciones de la Diabetes/prevención & control , Dipéptidos/farmacología , Cardiopatías/prevención & control , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Transducción de Señal/efectos de los fármacos , Adamantano/farmacología , Animales , Apoptosis , Diabetes Mellitus Experimental , Isoproterenol/toxicidad , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To determine the prevalence of unintentional injuries and its associated factors among under-five children in Rural Delhi. METHODS: This community based cross-sectional study was conducted in Pooth Khurd village of Delhi during 2018 among under-five children and their care givers. Primary caregivers of the child in the randomly selected households were interviewed using a semi-structured pretested questionnaire. Data related to unintentional injuries in past 12 months and its associated factors were collected. RESULTS: Unintentional injuries were prevalent in 29.3% (95% CI: 25.8-32.9) of the 650 under-five children included. Male children had 1.4 times increased prevalence of injuries (aPR=1.4, 95% CI: 1.1-1.7). As the age increases from 2 years to 5 years the prevalence of injuries increased constantly from 29% to 50%. The prevalence of unintentional injuries was significantly higher among children of working mothers (aPR=1.7, 95% CI: 1.4-2.1), family with more than 3 children (aPR=1.6, 95% CI:1.1-2.4), household without a separate kitchen (aPR=1.6, 95% CI:1.2-2.2) and household with inadequate lighting (aPR=1.8, 95% CI:1.4-2.3). CONCLUSIONS: The factors significantly associated with unintentional injuries were male gender, higher age of the children, maternal occupation, increased number of children in the family, not having a separate kitchen and inadequate lighting.
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Composición Familiar , Heridas y Lesiones , Niño , Preescolar , Estudios Transversales , Humanos , India/epidemiología , Lactante , Masculino , Prevalencia , Factores de Riesgo , Población Rural , Heridas y Lesiones/epidemiologíaRESUMEN
Isoproterenol (ISO) induced oxidative stress and inflammation is involved in the pathogenesis of myocardial necrosis. To optimize the effect of erdosteine against myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6), that is, normal, ISO-control, erdosteine pretreatment with ISO. Rats were administered erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to ISO-C and erdosteine treatment groups on the 27th and 28th day. On the 29th day, hemodynamic parameters were recorded and the heart was excised for further parameters. In ISO-C rats, significantly increased levels of inflammatory markers, pro-oxidants, and structural damage were observed as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed an increased expression of apoptotic proteins. Erdosteine at 80 mg/kg reversed the deleterious effects of ISO and normalized myocardium. Erdosteine showed anti-inflammatory, antiapoptotic, and antioxidant activities through inhibition of MAPK and Nrf-2/HO-1 pathways. To conclude, erdosteine was found protective in ISO-induced myocardial necrosis through MAPK and Nrf-2/HO-1 pathway.
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Cardiomiopatías/prevención & control , Hemo Oxigenasa (Desciclizante)/metabolismo , Sistema de Señalización de MAP Quinasas , Factor 2 Relacionado con NF-E2/metabolismo , Tioglicolatos/farmacología , Tiofenos/farmacología , Animales , Biomarcadores/metabolismo , Cardiomiopatías/inducido químicamente , Cardiomiopatías/enzimología , Cardiomiopatías/metabolismo , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Mediadores de Inflamación/sangre , Isoproterenol/farmacología , Masculino , Necrosis/prevención & control , Ratas , Transducción de Señal/efectos de los fármacos , Tioglicolatos/administración & dosificación , Tiofenos/administración & dosificaciónRESUMEN
The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study. Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ. A murine model of cardiac ischemia-reperfusion injury was used to explore this further. Male Wistar Rats were randomly assigned to five groups. Fisetin (20 mg/kg; p. o) was administered for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Fisetin pretreatment upregulated the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters, infarct size, ELISA for oxidative stress, immunohistochemistry and TUNEL assay for apoptosis, and western blot analysis for MAPK proteins and inflammation. PPAR-γ activation by fisetin led to significantly reduced infarct size, suppression of oxidative stress, reduction of cardiac injury markers, alleviation of inflammation, and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase, ERK1/ERK2 and suppression of JNK and p38 proteins. The aforementioned beneficial findings of fisetin were reversed on the administration of a specific antagonist of PPAR-γ. In conclusion, through our experiments, we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant. In conclusion, our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin. Hence, Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions.
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Cardiotónicos/uso terapéutico , Flavonoides/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , PPAR gamma/agonistas , Animales , Cardiotónicos/metabolismo , Flavonoides/metabolismo , Flavonoles , Corazón/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Simulación del Acoplamiento Molecular , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , PPAR gamma/metabolismo , Ratas Wistar , Regulación hacia ArribaRESUMEN
[This corrects the article DOI: 10.1155/2016/7580731.].
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While coronary artery disease (CAD) has become a major threat worldwide, the timely biomarker-based early diagnosis of CAD remains a major unmet clinical challenge. We aimed towards assessing the level of circulatory microRNAs as candidates of novel biomarkers in patients with CAD. A total of 147 subjects were recruited which includes 78 subjects with angiographically proven CAD, 15 pre-atherosclerotic normal coronary artery (NCA) subjects and 54 healthy individuals. Quantitative real-time PCR assays were performed. MiR-133b was downregulated by 4.6 fold (p < 0.0001) whereas miR-21 was upregulated by ~2 fold (p < 0.0001) in plasma samples of CAD patients. Importantly, both the miRNAs showed association with disease severity as miR-133b was downregulated by 8.45 fold in acute coronary syndrome (ACS), 3.38 fold in Stable angina (SA) and 2.08 fold in NCA. MiR-21 was upregulated by 2.46 fold in ACS, 1.90 fold in SA and 1.12 fold in NCA. Moreover, miR-133b could significantly differentiate subjects with ST-elevation myocardial infarction (STEMI) from Non-STEMI. Area under the curve (AUC) for miR-133b was 0.80 with >75.6% sensitivity and specificity, AUC for miR-21 was 0.79 with >69.4% sensitivity and specificity. Our results suggest that miR-133b and miR-21 could be possible candidates of novel biomarkers in early prediction of CAD.
Asunto(s)
Biomarcadores/sangre , MicroARN Circulante/genética , Enfermedad de la Arteria Coronaria/diagnóstico , Regulación de la Expresión Génica , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Humanos , Masculino , MicroARNs/sangre , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Oxidative stress plays an important role in the pathogenesis of myocardial ischemia-reperfusion (IR) injury. Morin, a bioflavonoid, has demonstrated antioxidant, anti-inflammatory and other diverse pharmacological activities in various experimental models such as isoproterenol-induced myocardial injury, doxorubicin-induced cardiotoxicity and neurotoxicity, as well as cisplatin-induced nephrotoxicity. Thus, this study aimed to evaluate the effect of morin in myocardial IR injury model and its underlying mechanisms. METHOD: To accomplish this, male albino Wistar rats were pre-treated with morin (40 and 80 mg/kg; po) for 28 days and on 29th day, rats experienced 45-min myocardial ischemia followed by 60-min reperfusion. RESULTS: In comparison to IR-control group, morin pre-treatment significantly normalized hemodynamic parameters, restored antioxidant status, improved pathological changes, reduced the release of cardiac injury markers, inhibited inflammation (TNF-α/IL-6/NFκB/IKKß) and apoptosis (increased Bcl-2, decreased Bax/Caspase-3 and TUNEL positivity) in the myocardium. This improvement in antioxidant, inflammation and anti-apoptosis markers could be due to downregulation of SAPK (p38/JNK) pathway and upregulation of survival kinase, i.e. RISK pathway (ERK/eNOS) in the myocardium. CONCLUSION: Thus, morin attenuated myocardial IR injury in rats by regulation of RISK/SAPK pathways.
Asunto(s)
Antioxidantes/uso terapéutico , Flavonoides/uso terapéutico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Antioxidantes/farmacología , Relación Dosis-Respuesta a Droga , Flavonoides/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models. AIM: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism. METHODS: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters. RESULTS: As compared to cisplatin-control group, Ber pretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin mediated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney. CONCLUSION: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/ PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.