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BACKGROUND: Online video hosting websites such as YouTube have been increasingly used by medical institutions to spread information about new and exciting topics. However, due to the large number of videos uploaded daily and the lack of peer review, few attempts have been made to assess the quantity and quality of information that is uploaded on YouTube. For this study, our team assessed the available content on the transoral robotic surgery (TORS) procedure. METHODS: A qualitative case study model was employed. Videos related to TORS were collected using a unified search protocol. Each video was then analyzed, and metrics of the following data points were collected: views, likes, comments, upload date, length of video, author type, author, and region of origin. Each dataset was analyzed by two distinct authors, and interrater reliability was calculated. Quantitative and qualitative statistics were curated. RESULTS: A total of 124 videos were analyzed for this review. The breakdown of videos was as follows: 15.32% (19) in the educational for patients category, 16.94% (21) in the educational for trainees category, 30.65% (38) in the procedural overview category, 8.87% (11) in the patient experience (PE) category, 10.48% (13) in the promotional category, 12.10% (15) in the other category, and 5.65% (7) in the irrelevant (IR) category. The total number of views across all videos analyzed was 2,589,561. The total number of likes was 14,827, and the total number of comments was 2,606. The average video length was 8.63 minutes. The most viewed category was the PE category at 1,014,738 and the most liked at 1,714. The least viewed category was IR at 21,082. The PE category had the most engagement based on combined comments and likes. The most watched video, with 774,916 views, was in the PE category under the "TORS for Thyroidectomy" search term and was titled "Thyroid Surgery (Thyroidectomy)." CONCLUSION: As the prevalence of online videos regarding medical devices, procedures, and treatments increases, patients and trainees alike will look toward resources such as YouTube to augment their understanding. Patients, providers, and medical education platforms should take heed of the promise and pitfalls of medical content on YouTube.
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The building sector is growing at a rapid rate, leading to an increased demand for construction materials. Concrete made with Ordinary Portland Cement (OPC) has long been the preferred choice due to its excellent bonding properties and versatility as demanded by construction process. However, the manufacturing of Ordinary Portland Cement (OPC) leads to negative impacts on the environment, with the cement sector responsible for around 5-8% of global CO2 emissions. In addition, the manufacture of OPC necessitates significant amounts of natural raw materials and energy. Contrastingly, using geopolymers promises to save substantial amounts of energy and reduce CO2 emissions. This potential has sparked growing interest in the application of geopolymers within transportation infrastructure. For pavements, the workability requirement is less, and hence, geopolymer concrete (GPC) is a viable option, but fatigue-resistance of GPC is not seen reported in literatures. This article evaluates the properties of geopolymer concrete with low-calcium fly ash partially replaced with ground granular blast furnace slag (GGBS) with 8 M NaOH alkaline solution and cured under ambient atmospheric conditions to evaluate its usage in pavements and develop an environmentally sustainable and durable GPC capable of withstanding heavy traffic. The study involves adjusting the pavement quality concrete (PQC) mix design; evaluating the mechanical characteristics, abrasion resistance, and shrinkage strain of the GPC; and analyzing its microstructure. Additionally, the study compares the fatigue life of GPC to that of PQC using various Weibull distribution approaches. The results showed that GPC4 (70% Fly ash and 30% GGBS) mix achieved best results at 28 days, with a compressive strength of 45.68 MPa, split tensile strength of 3.76 MPa, and flexural strength of 4.62 MPa. Also, shrinkage strains were nearly 31% lesser than PQC at 90 days. In addition, developing GPC needs 27% lesser embodied energy than PQC. Fatigue analysis prove that ambient cured fly ash-GGBS based geopolymer concrete with 8 M NaOH exhibits less stress development than PQC at medium loads, even though it is brittle. Thus, the study proves that it is suitable as a material for pavements to resist medium-loaded traffic-resisting pavements.
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The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-ß accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.
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AVC Isquêmico , Doenças do Sistema Nervoso , Doença de Parkinson , Acidente Vascular Cerebral , Humanos , Transplante de Microbiota Fecal , Doenças do Sistema Nervoso/terapia , Acidente Vascular Cerebral/terapiaRESUMO
The pubic symphyseal surface is one of the reliable parameters used to estimate age, as it consistently shows degenerative observational variations throughout the lifespan, particularly from the 3rd decade onwards. These changes have been extensively studied to generate population-specific models for forensic age estimation. In the past, there have been many studies used to estimate age at death from the pubis symphysis using skeletal remains. However, due to dearth of contemporary skeletal repositories, and the resource intensive maceration process required for obtaining examination quality bones, studies on cadaver are difficult to conduct. Moreover, due to recent advancements in the science of medical imaging, newer radiological modalities like computed tomography (CT) can be used to visualize previously inaccessible areas such as the pubic symphysis in cadavers and the living alike, and subsequent age estimation is feasible. Recently, Chen et al. (2008, 2011) conducted a study on the cadaveric Chinese Han population in both males and females separately by using nine morphological changes and scoring them according to the changes that occurred. The present study aimed to estimate an individual's age using CT images of the pubic symphysis, by applying the scoring method for its morphological changes given by Chen et al. The present study was conducted on 263 randomly selected participants (Males = 154, Females = 109), who came for diagnostic purposes to the hospital. The CT images of these individuals were collected after obtaining ethical approval and proper consent from the study participants. Each of the morphological indicators was assessed, and appropriate scores were given according to criteria given by Chen et al. In the present study, both linear and multiple regression models to estimate age using the pubic symphyseal morphological changes were developed. From the results of the present study, it was concluded that the Chen et al. scoring method can be used to accurately estimate age from 3DCT images of the living, and the models derived in the present study could be applicable to individuals from the Indian subcontinent.
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Determinação da Idade pelo Esqueleto , Sínfise Pubiana , Tomografia Computadorizada por Raios X , Humanos , Sínfise Pubiana/diagnóstico por imagem , Sínfise Pubiana/anatomia & histologia , Determinação da Idade pelo Esqueleto/métodos , Feminino , Masculino , Índia , Tomografia Computadorizada por Raios X/métodos , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Imageamento Tridimensional/métodos , Adolescente , Idoso de 80 Anos ou maisRESUMO
The increasing comorbidity of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) associated with traumatic brain injury (TBI) is a serious medical, economic, and social issue. However, the molecular toxicology and pathophysiological mechanisms of comorbid AUD and PTSD are not well understood and the identification of the comorbidity state markers is significantly challenging. This review summarizes the main characteristics of comorbidity between AUD and PTSD (AUD/PTSD) and highlights the significance of a comprehensive understanding of the molecular toxicology and pathophysiological mechanisms of AUD/PTSD, particularly following TBI, with a focus on the role of metabolomics, inflammation, neuroendocrine, signal transduction pathways, and genetic regulation. Instead of a separate disease state, a comprehensive examination of comorbid AUD and PTSD is emphasized by considering additive and synergistic interactions between the two diseases. Finally, we propose several hypotheses of molecular mechanisms for AUD/PTSD and discuss potential future research directions that may provide new insights and translational application opportunities.
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Alcoolismo , Lesões Encefálicas Traumáticas , Transtornos de Estresse Pós-Traumáticos , Humanos , Alcoolismo/complicações , Alcoolismo/epidemiologia , Alcoolismo/metabolismo , Comorbidade , Consumo de Bebidas Alcoólicas , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/epidemiologiaRESUMO
The microbiota-gut-brain axis (MGBA) is important in maintaining the structure and function of the central nervous system (CNS) and is regulated by the CNS environment and signals from the peripheral tissues. However, the mechanism and function of the MGBA in alcohol use disorder (AUD) are still not completely understood. In this review, we investigate the underlying mechanisms involved in the onset of AUD and/or associated neuronal deficits and create a foundation for better treatment (and prevention) strategies. We summarize recent reports focusing on the alteration of the MGBA in AUD. Importantly, we highlight the properties of small-molecule short-chain fatty acids (SCFAs), neurotransmitters, hormones, and peptides in the MGBA and discusses their usage as therapeutic agents against AUD.
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Alcoolismo , Humanos , Alcoolismo/tratamento farmacológico , Eixo Encéfalo-Intestino , Encéfalo , Sistema Nervoso CentralRESUMO
Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.
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With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its "double-edged sword", autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs.
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Envelhecimento/genética , Doença de Alzheimer/prevenção & controle , Esclerose Lateral Amiotrófica/prevenção & controle , Doença de Huntington/prevenção & controle , Melatonina/farmacologia , Doença de Parkinson/prevenção & controle , Envelhecimento/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteínas Relacionadas à Autofagia/agonistas , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Ritmo Circadiano/fisiologia , Humanos , Doença de Huntington/genética , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Melatonina/biossíntese , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/metabolismo , Sistema Nervoso/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Glândula Pineal/fisiologiaRESUMO
Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), increase as the population ages around the world. Environmental factors also play an important role in most cases. Alcohol consumption exists extensively and it acts as one of the environmental factors that promotes these neurodegenerative diseases. The brain is a major target for the actions of alcohol, and heavy alcohol consumption has long been associated with brain damage. Chronic alcohol intake leads to elevated glutamate-induced excitotoxicity, oxidative stress and permanent neuronal damage associated with malnutrition. The relationship and contributing mechanisms of alcohol with these three diseases are different. Epidemiological studies have reported a reduction in the prevalence of Alzheimer's disease in individuals who drink low amounts of alcohol; low or moderate concentrations of ethanol protect against ß-amyloid (Aß) toxicity in hippocampal neurons; and excessive amounts of ethanol increase accumulation of Aß and Tau phosphorylation. Alcohol has been suggested to be either protective of, or not associated with, PD. However, experimental animal studies indicate that chronic heavy alcohol consumption may have dopamine neurotoxic effects through the induction of Cytochrome P450 2E1 (CYP2E1) and an increase in the amount of α-Synuclein (αSYN) relevant to PD. The findings on the association between alcohol consumption and ALS are inconsistent; a recent population-based study suggests that alcohol drinking seems to not influence the risk of developing ALS. Additional research is needed to clarify the potential etiological involvement of alcohol intake in causing or resulting in major neurodegenerative diseases, which will eventually lead to potential therapeutics against these alcoholic neurodegenerative diseases.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Doença de Alzheimer/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Doença de Parkinson/metabolismo , Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/toxicidade , Esclerose Lateral Amiotrófica/induzido quimicamente , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Progressão da Doença , Etanol/efeitos adversos , Etanol/toxicidade , Humanos , Doenças Neurodegenerativas/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fatores de Risco , alfa-SinucleínaRESUMO
Alcohol use disorder (AUD) is an enormous public health problem that poses significant social, medical, and economic burdens. Under AUD, the liver is one of the most adversely affected organs. As current therapies and protective drugs for AUD-mediated liver injury are very limited, the prevention and therapy of alcoholic liver disease are urgently needed. The present study aims to investigate the beneficial effects of tartary buckwheat extract (TBE), the important component of Maopu tartary buckwheat liquor, on both alcoholic-induced acute and chronic liver injuries. We show that the TBE administration, similar to curcumin, significantly reduces the elevated serum aspartate aminotransferase and alanine aminotransferase levels, improves liver index, alleviates the elevated contents of hepatic malondialdehye, and restores the decreased contents of hepatic glutathione both in acute and chronic liver injuries in alcohol-exposed rats. Furthermore, histopathological analyses show that a medium dose of TBE (16.70 ml/kg body weight) alleviates hepatocyte morphology changes in both acute and chronic alcohol exposure models. We also show the protective effects of TBE on the cell death rates of alcohol-exposed primary cultured hepatocytes, HepG2 hepatoma, and Huh 7 hepatoma cells. Furthermore, we demonstrate that TBE exerts hepatoprotection partly through inhibiting the mitochondrial cell death pathway by reducing cytochrome c release, caspase-9 and -3 activities, and the number of TUNEL-positive cells. These effects of TBE were accompanied by enhanced levels of Bcl-2 and Bcl-xL and autophagic cell death pathway by reducing Beclin-1 expression, as well as through promoting its anti-oxidant capacity by suppressing reactive oxygen species production. This study demonstrates, for the first time, the protective effect of TBE against alcohol-induced acute and chronic liver injury in vivo and in vitro. Given the dietary nature of tartary buckwheat, pueraria, lycium barbarum, and hawthorn, the oral intake of TBE or liquor contained TBE, e.g., Maopu Tartary buckwheat liquor, compared with pure liquor consumption alone, may have the potential to alleviate alcoholic-induced liver injuries.
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The purpose of this review is to briefly summarize the roles of alcohol (ethanol) and related compounds in promoting cancer and inflammatory injury in many tissues. Long-term chronic heavy alcohol exposure is known to increase the chances of inflammation, oxidative DNA damage, and cancer development in many organs. The rates of alcohol-mediated organ damage and cancer risks are significantly elevated in the presence of co-morbidity factors such as poor nutrition, unhealthy diets, smoking, infection with bacteria or viruses, and exposure to pro-carcinogens. Chronic ingestion of alcohol and its metabolite acetaldehyde may initiate and/or promote the development of cancer in the liver, oral cavity, esophagus, stomach, gastrointestinal tract, pancreas, prostate, and female breast. In this chapter, we summarize the important roles of ethanol/acetaldehyde in promoting inflammatory injury and carcinogenesis in several tissues. We also review the updated roles of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) and other cytochrome P450 isozymes in the metabolism of various potentially toxic substrates, and consequent toxicities, including carcinogenesis in different tissues. We also briefly describe the potential implications of endogenous ethanol produced by gut bacteria, as frequently observed in the experimental models and patients of nonalcoholic fatty liver disease, in promoting DNA mutation and cancer development in the liver and other tissues, including the gastrointestinal tract.
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Transtornos Relacionados ao Uso de Álcool , Carcinogênese , Citocromo P-450 CYP2E1 , Sistema Enzimático do Citocromo P-450 , Etanol , Acetaldeído/toxicidade , Transtornos Relacionados ao Uso de Álcool/fisiopatologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Citocromo P-450 CYP2E1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Etanol/toxicidade , Humanos , Isoformas de ProteínasRESUMO
Huntington's disease (HD) is a hereditary neurodegenerative disease of the central nervous system (CNS). Onset of HD occurs between the ages of 30 and 50 years, although few cases are reported among children and elderly. HD appears to be less common in some populations such as those of Japanese, Chinese, and African descent. Clinical features of HD include motor dysfunction (involuntary movements of the face and body, abnormalities in gait, posture and balance), cognitive impairment (obsessive-compulsive disorder), and psychiatric disorders (dementia). Mutation in either of the two copies of a gene called huntingtin (HTT), which codes genetic information for a protein called "huntingtin (Htt)", precipitates the disease in an individual. Expansion of cytosine-adenine-guanine (CAG) triplet repeats in the HTT gene results in an abnormal Htt protein. Intracellular neuronal accumulation of the mutated Htt protein (mHtt) causes distinctive erratic movements associated with HD. Further, excessive accumulation of the HTT gene repeats causes abnormal production of reactive oxygen species (ROS) and the ensuing mitochondrial (MT) oxidative stress in neurons. Since there is neither a cure nor a promising strategy to delay onset or progression of HD currently available, therapeutics are mainly focusing only on symptomatic management. Several studies have shown that MT dysfunction-mediated oxidative stress is a key factor for the neurodegeneration observed in HD. Supplementation of antioxidants and nutraceuticals has been widely studied in the management of oxidative damage, an associated complication in HD. Therefore, various antioxidants are used as therapeutics for managing and/or treating HD. The present review aimed at delving into the abnormal cellular changes and energy kinetics of the neurons expressing the mHtt gene and the therapeutic roles of antioxidants in HD.
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Antioxidantes/uso terapêutico , Doença de Huntington/terapia , Fármacos Neuroprotetores/uso terapêutico , Animais , Humanos , Doença de Huntington/metabolismoRESUMO
Alzheimer's disease (AD ) is mounting as social and economic encumbrance which are accompanied by deficits in cognition and memory. Over the past decades, Alzheimer's disease (AD) holds the frontline as one of the biggest healthcare issues in the world. AD is an age related neurodegenerative disorder marked by a decline in memory and an impairment of cognition. Inspite of tedious scientific effort, AD is still devoid of pharmacotherapeutic strategies for treatment as well as prevention. Current treatment strategies using drugs are symbolic in nature as they treat disease manifestation though are found effective in treating cognition. Inclination of science towards naturopathic treatments aiming at preventing the disease is highly vocal. Application of marine-derived bioactive compounds, has been gaining attention as mode of therapies against AD. Inspired by the vastness and biodiversity richness of the marine environment, role of marine metabolites in developing new therapies targeting brain with special emphasis to neurodegeneration is heading as an arable field. This review summarizes select-few examples highlighted as therapeutical applications for neurodegenerative disorders with special emphasis on AD.
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Doença de Alzheimer/tratamento farmacológico , Organismos Aquáticos/química , Fatores Biológicos/uso terapêutico , Doença de Alzheimer/etiologia , HumanosRESUMO
Extracellular vesicles (EVs) are small membranous vesicles originating from various cells and tissues, including the liver parenchymal hepatocytes and nonparenchymal cells such as Kupffer and stellate cells. Recently, the pathophysiological role of EVs, such as exosomes and microvesicles, has been increasingly recognized based on their properties of intercellular communications. These EVs travel through the circulating blood and interact with specific cells and then deliver their cargos such as nucleic acids and proteins into recipient cells. In addition, based on their stabilities, circulating EVs from body fluids such as blood, cerebrospinal fluid, urine, saliva, semen, breast milk and amniotic fluids are being studied as a valuable source of potential biomarkers for providing information about the physiological status of original cells or tissues. In addition, EVs are considered potential therapeutic agents due to their ability for intercellular communications between different cell types within the liver and between various organs through transfer of their cargos. In this review, we have briefly described recent advances in the characteristics and pathophysiological roles of EVs in alcoholic liver disease (ALD) or drug-induced liver injury (DILI) and discuss their advantages in the discovery of potential biomarkers and therapeutic agents.
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Doença Hepática Induzida por Substâncias e Drogas , Vesículas Extracelulares , Hepatopatias Alcoólicas , Animais , Biomarcadores , HumanosRESUMO
Patients who suffer from alcohol use disorders (AUDs) usually go through various socio-behavioral and pathophysiological changes that take place in the brain and other organs. Recently, consumption of unhealthy food and excess alcohol along with a sedentary lifestyle has become a norm in both developed and developing countries. Despite the beneficial effects of moderate alcohol consumption, chronic and/or excessive alcohol intake is reported to negatively affect the brain, liver and other organs, resulting in cell death, organ damage/failure and death. The most effective therapy for alcoholism and alcohol related comorbidities is alcohol abstinence, however, chronic alcoholic patients cannot stop drinking alcohol. Therefore, targeted therapies are urgently needed to treat such populations. Patients who suffer from alcoholism and/or alcohol abuse experience harmful effects and changes that occur in the brain and other organs. Upon stopping alcohol consumption, alcoholic patients experience acute withdrawal symptoms followed by a protracted abstinence syndrome resulting in the risk of relapse to heavy drinking. For the past few decades, several drugs have been available for the treatment of AUDs. These drugs include medications to reduce or stop severe alcohol withdrawal symptoms during alcohol detoxification as well as recovery medications to reduce alcohol craving and support abstinence. However, there is no drug that completely antagonizes the adverse effects of excessive amounts of alcohol. This review summarizes the drugs which are available and approved by the FDA and their mechanisms of action as well as the medications that are under various phases of preclinical and clinical trials. In addition, the repurposing of the FDA approved drugs, such as anticonvulsants, antipsychotics, antidepressants and other medications, to prevent alcoholism and treat AUDs and their potential target mechanisms are summarized.
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Alcoolismo/tratamento farmacológico , Animais , Aprovação de Drogas , Reposicionamento de Medicamentos , Humanos , Transdução de Sinais , Estados Unidos , United States Food and Drug AdministrationRESUMO
The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. Moreover, ILF attenuated rotenone induced toxicity by down-regulating Bax, caspases-3, 6, 8 and 9 expression and up-regulating of Bcl-2 expression. Furthermore regulation of p-P13K, p-AKT and p-GSK-3 beta expression by ILF, clearly confirmed its protective effects. Taken together, our results suggested that ILF attenuated rotenone-induced oxidative stress, mitochondrial dysfunction and apoptosis through the regulation of P13K/AKT/GSK-3 beta signaling pathways. However further pre-clinical studies are warranted in rodents to use ILF as a promising therapeutic agent for PD in future.
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Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Rotenona/farmacologia , Sesquiterpenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Neuroblastoma , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field.
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Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Citocromo P-450 CYP2E1/metabolismo , Mitocôndrias/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Peroxidação de Lipídeos , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo , Processamento de Proteína Pós-Traducional , Transdução de SinaisRESUMO
Alzheimer's disease (AD) is the most common form of dementia that mainly affects the cognitive functions of the aged populations. Trigonella foenum-graecum (L.) (fenugreek), a traditionally well utilized medicinal plant ubiquitously used as one of the main food additive worldwide, is known to have numerous beneficial health effects. Fenugreek seed extract could be able to inhibit the activity of acetylcholinesterase (AChE), a key enzyme involved in the pathogenesis of AD, and further shown to have anti-parkinsonic effect. The present study was aimed to explore the neuroprotective effect of fenugreek seed powder (FSP) against aluminium chloride (AlCl3) induced experimental AD model. Administration of germinated FSP (2.5, 5 and 10% mixed with ground standard rat feed) protected AlCl3 induced memory and learning impairments, Al overload, AChE hyperactivity, amyloid ß (Aß) burden and apoptosis via activating Akt/GSK3ß pathway. Our present data could confirm the neuroprotective effect of fenugreek seeds. Further these results could lead a possible therapeutics for the management of neurodegenerative diseases including AD in future.
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Compostos de Alumínio/toxicidade , Apoptose/efeitos dos fármacos , Cloretos/toxicidade , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Cloreto de Alumínio , Peptídeos beta-Amiloides/metabolismo , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Plantas Medicinais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Trigonella , Redução de Peso/efeitos dos fármacosRESUMO
The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene's sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities.