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1.
Front Biosci (Landmark Ed) ; 28(8): 169, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37664941

RESUMO

BACKGROUND: Methods like the bio-synthesis of silver nanoparticles (Ag NPs) using plant extracts have become promising due to their eco-friendly approach. The study aimed to examine the utilization of Garcinia gummi-gutta fruit phytochemicals as agents in the biosynthesis of Ag NPs, evaluation of the antimicrobial, antioxidant, and anti-cancerous properties, as well as the photocatalytic ability of bio-synthesized Ag NPs against Crystal Violet (CV), a triphenylmethane dye. METHODS: The characterization of the physical properties of the Ag NPs synthesized via the green route was done using UV-Vis spectrophotometry (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared Spectrophotometry (FTIR), Scanning Electron Microscopy (SEM), Zeta potential analysis, and Transmission Electron Microscopy (TEM). The dye degradation efficiency of CV was determined using synthesized Ag NPs under UV light by analyzing the absorption maximum at 579 nm. The antimicrobial efficacy of Ag NPs against E. coli, S. aureus, Candida tropicalis, and Candida albicans was examined using the broth dilution method. The antioxidant and anti-cancer properties of the synthesized Ag NPs were assessed using the DPPH and MTT assays. RESULTS: The UV analysis revealed that the peak of synthesized Ag NPs was 442 nm. Data from FTIR, XRD, Zeta potential, SEM, and TEM analysis confirmed the formation of nanoparticles. The SEM and TEM analysis identified the presence of spherical nanoparticles with an average size of 29.12 nm and 24.18 nm, respectively. Maximum dye degradation efficiency of CV was observed at 90.08% after 320 min without any silver leaching, confirming the photocatalytic activity of Ag NPs. The bio-efficiency of the treatment was assessed using the Allium cepa root growth inhibition test, toxicity analysis on Vigna radiata, and Brine shrimp lethality assay. CONCLUSIONS: The findings revealed the environmentally friendly nature of green Ag NPs over physical/chemically synthesized Ag NPs. The synthesized Ag NPs can effectively be used in biomedical and photocatalytic applications.


Assuntos
Anti-Infecciosos , Garcinia , Nanopartículas Metálicas , Neoplasias , Antioxidantes/farmacologia , Prata/farmacologia , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Violeta Genciana
2.
Asian Pac J Cancer Prev ; 24(2): 357-361, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36853282

RESUMO

INTRODUCTION: The most significant industrial utilization of carbon disulfide (CS2) has been in the manufacture of cellulose rayon, cellophane, and rubber industry. CS2 prompts expanded recurrence of chromosomal variations in laborers occupationally exposed to CS2. MATERIALS AND METHODS: In the current study, the DNA analysis was carried out from exfoliated buccal epithelial cells from rubber industry workers exposed to CS2 and an equal number of healthy control subjects. Both the control and experimental subjects were categorized by their smoking habits such as smokers (S) and non-smokers (NS). Furthermore, experimental subjects were further separated based on their exposure period. Students t-test statistical tools were used to analyze the final results. RESULTS: The present analysis identified a high frequency of DNA damage in rubber industry workers (16.55±0.43) than control subjects (9.8±0.21). Also, maximum number of DNA damage detected in smoking experimental group (18.27±0.02) than non-smoking experimental (15.02±0.01) and smoking control groups (10.25±0.04 ). CONCLUSION: Smoking habits synergistically increased the DNA damage in the rubber industry workers exposed to CS2.


Assuntos
Dissulfeto de Carbono , Humanos , Dissulfeto de Carbono/efeitos adversos , Borracha/efeitos adversos , Dano ao DNA , Comércio , Células Epiteliais
3.
Environ Mol Mutagen ; 64(2): 123-131, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36541415

RESUMO

Recent technological advances in the medical field have increased the plausibility of exposing humans to high-intensity wavelength radiations like x-rays and gamma rays while diagnosing or treating specific medical maladies. These radiations induce nucleotide changes and chromosomal alterations in the exposed population, intentionally or accidentally. A radiological investigation is regularly used in identifying the disease, especially by the technicians working in intensive care units. The current study observes the genetic damages like chromosomal abnormalities (CA) in clinicians who are occupationally exposed to high-intensity radiations (x-rays) at their workplaces using universal cytogenetic tools like micronucleus assay (MN), sister chromatid exchange and comet assay. The study was conducted between 100 exposed practitioners from the abdominal scanning, chest scanning, cranial and orthopedic or bone scanning department and age-matched healthy controls. We observed a slightly higher rate of MN and CA (p < .05) in orthopedic and chest department practitioners than in other departments concerning increasing age and duration of exposure at work. Our results emphasize taking extra precautionary measures in clinical and hospital radiation laboratories to protect the practitioners.


Assuntos
Dano ao DNA , Exposição Ocupacional , Humanos , Raios X , Radiografia , Raios gama , Aberrações Cromossômicas , Hospitais , Testes para Micronúcleos/métodos , Linfócitos
4.
Molecules ; 27(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36296552

RESUMO

The tracing of an alternative drug, Phytochemicals is a promising approach to the viral threats that have emerged over the past two years. Across the world, herbal medicine is a better solution against anti-viral diseases during pandemic periods. Goniothalamus wightii is an herbal plant, which has diverse bioactive compounds with anticancer, antioxidant, and anti-viral properties. The aim of the study was to isolate the compound by chromatography studies and functionalization by FT-IR, LC-MS, and NMR (C-NMR, H-NMR). As a result, the current work focuses on whether (S)-Goniathalamin and its analogue could act as natural anti-viral molecules for multiple target proteins viz., MPro, RdRp, and SPro, which are required for SARS-CoV-2 infection. Overall, 954 compounds were examined and the molecular-docking studies were performed on the maestro platform of Schrodinger software. Molecular-dynamics simulation studies were performed on two complex major compounds to confirm their affinity across 150 simulations. This research suggests that plant-based drugs have high levels of antiviral properties against coronavirus. However, more research is needed to verify its antiviral properties.


Assuntos
Tratamento Farmacológico da COVID-19 , Goniothalamus , Humanos , SARS-CoV-2 , Proteases 3C de Coronavírus , Antioxidantes , Espectroscopia de Infravermelho com Transformada de Fourier , Cisteína Endopeptidases/química , Antivirais/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , RNA Polimerase Dependente de RNA
5.
Drug Dev Ind Pharm ; 48(9): 480-490, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36165580

RESUMO

BACKGROUND: Cervical cancer continues to be the leading cause of death worldwide despite the availability of many therapeutic options. Biogenic synthesis of metal nanoparticles paves a new way for the development of targeted drug delivery modalities of cancer therapeutics. OBJECTIVE: In this study, we demonstrate the efficacy of biosynthesized silver nanoparticles from methanolic leaf extract of Citrus hystrix as an anticancer agent used against cervical cancer cell line HeLa. METHODS: The addition of 1 mM silver nitrate to methanolic leaf extract of Citrus hystrix resulted in the biosynthesis of silver nanoparticles during the reaction mixture and was incubated in the dark for 1 h at pH 9 with gentle stirring. Characterization of synthesized NPs was carried out using various analyses. MTT assay, DAPI, AO/EB double staining, and reverse transcriptase-PCR (RT-PCR) analysis were carried out to evaluate the cytotoxic activity of Citrus hystrix mediated green synthesized silver nanoparticles (ChAgNPs). RESULTS AND CONCLUSION: The absorption band at 430 nm, as shown by UV-vis spectroscopy revealed the formation of AgNPs. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis shows that most of the ChAgNPs were spherical in shape and X-ray diffraction (XRD) patterns revealed the crystalline nature of the particles. Moreover, its potent cytotoxic effect on the HeLa cell line was analyzed using MTT assay with an IC50 value of 56 µg/ml by decreasing the cell viability in a dose and time-dependent manner. The induced apoptotic activity was confirmed by DAPI and double staining methods. Autophagic and apoptotic mediated cell death in ChAgNPs treated HeLa cell line was confirmed by staining procedures and RT-PCR methods.


Assuntos
Antineoplásicos , Citrus , Nanopartículas Metálicas , Neoplasias do Colo do Útero , Humanos , Feminino , Células HeLa , Nanopartículas Metálicas/química , Neoplasias do Colo do Útero/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Prata , Antineoplásicos/química , Antibacterianos/química
6.
Artigo em Inglês | MEDLINE | ID: mdl-35911161

RESUMO

Carrageenan, a sulfated polysaccharide, was produced by certain species of marine red seaweeds, which have been used as a significant source of food, feed, and antibiotic agent throughout history due to their alleged human health benefits. The present study aimed to derive the polysaccharides from Hypnea valentiae and describe the biological applications. Carrageenan was characterized by FT-IR, C-NMR, AFM, and their antimicrobial, antioxidant, and anticoagulant capabilities; furthermore, the larvicidal effect of methanol extract was generated from the seaweed against Aedes aegypti larvae at various concentrations. The molecular docking experiments were carried out computationally for finding the molecular insight of the macromolecules and small molecules' interaction using GLIDE docking by using Schrodinger software. Antibacterial zones of inhibition in different concentrations are compared with the 40 mg/mL higher activity against bacterial pathogens. Carrageenan is strong in all antioxidant activities, with the overall antioxidant (70.1 ± 0.61%) of radical at 250 µg/mL concentration being exhibited. The DPPH scavenging is effective in the inhibition of (65.74 ± 0.58%) radical at a concentration of 160 µg/mL and the hydroxyl scavenging (65.72 ± 0.60%) of activity at a concentration of 125 µg/mL being exhibited. Anticoagulant activities (APPT and PT) of carrageenan fraction were tested. H. valentiae and heparin sulphate shows higher activity of APTT (106.50 IU at 25 µg/mL) in comparison with the PT test (57.86 IU at 25 µg/mL) and the methanol extraction of higher larvicidal activity on A. aegypti (LC50 = 99.675 µg/mL). In this study, the carrageenan was exploited through in vitro and in silico molecular docking studies against antimicrobial, antioxidant, and anticoagulant properties. The results were establishing the potentiality of the carrageenan which is an alternative source to control the mosquitocidal property in the future. Moreover, molecular docking of carrageenan against multiple targets results in -7 to -6 Kcal/mol binding score. Findings of carrageen from in vitro to in silico studies are needed for further validation of clinical pieces of evidence.

7.
Toxicon ; 213: 59-75, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35452686

RESUMO

Ochratoxin A (OTA) is a toxic metabolite produced by Aspergillus and Penicillium fungi commonly found in raw plant sources and other feeds. This review comprises an extensive evaluation of the origin and proprieties of OTA, toxicokinetics, biotransformation, and toxicodynamics of ochratoxins. In in vitro and in vivo studies, the compatibility of OTA with oxidative stress is observed through the production of free radicals, resulting in genotoxicity and carcinogenicity. The OTA leads to nephrotoxicity as the chief target organ is the kidney. Other OTA excretion and absorption rates are observed, and the routes of elimination include faeces, urine, and breast milk. The alternations in the Phe moiety of OTA are the precursor for the amino acid alternation, bringing about Phe-hydroxylase and Phe-tRNA synthase, resulting in the complete dysfunction of cellular metabolism. Biodetoxification using specific microorganisms decreased the DNA damage, lipid peroxidation, and cytotoxicity. This review addressed the ability of antioxidants and the dietary components as prophylactic measures to encounter toxicity and demonstrated their capability to counteract the chronic exposure through supplementation as feed additives.


Assuntos
Ocratoxinas , Penicillium , Animais , Aspergillus/metabolismo , Humanos , Gado/metabolismo , Ocratoxinas/metabolismo , Ocratoxinas/toxicidade
8.
J Reprod Immunol ; 150: 103473, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35030354

RESUMO

Placenta is a crucial source of Tissue Factor (TF) to initiate coagulation. As far as the TF is concern, aberrant expression of TF has been reported to have a significant role in thrombosis, inflammation, cancer metastasis and atherosclerosis. It is evident that TF and TF-FVIIa complex has major roles in the disease process beyond hemostasis and thrombosis. On the other hand, TF-FVII-dependent signaling primarily activates PAR2 and inducing pro-angiogenic and immune-modulating cytokines in tumor environment. However, the role of TF has not been delineated in placental functions. Integrin typically binds to the extracellular matrix which in turn mediate cell-cell adhesion and cell behavior for migration. Dysregulation of integrin expression affects cell interaction, proliferation, and migration. Therefore, this study aims to ascertain the expression of TF in HTR-8/SVneo trophoblast cell line and its role in signal transduction of integrin (ITGα1, ITGα2, ITGß1) regulation concerning the invasion of trophoblasts. We have used RT-PCR and Western blot for the gene and protein expression analysis respectively. In addition, cell migration assays, MTT, and DAPI were performed to examine migration, cytotoxicity and apoptosis effect of FVIIa. The results suggest that the gene and protein level expressions of TF were predominant in HTR-8/SVneo cell line. Further, the cytotoxicity and apoptosis in HTR-8/SVneo cells were not observed when treated with FVIIa. The cells treated with FVIIa shown a dose-dependent up-regulation of integrin(s) (**p < 0.01, *p < 0.05) when compared to control. Migration of the HTR-8/SVneo cells was observed without any apoptosis in FVIIa-treated cells when compared to that of control. On the whole, these observations delineated the TF-FVIIa interaction in modulating the TF-dependent integrin signal transduction in HTR-8/SVneo trophoblast cell line.


Assuntos
Tromboplastina , Trofoblastos , Movimento Celular , Feminino , Humanos , Integrinas/metabolismo , Placenta/metabolismo , Gravidez , Tromboplastina/genética , Tromboplastina/metabolismo , Trofoblastos/metabolismo
9.
Biol Trace Elem Res ; 200(6): 2684-2697, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34448982

RESUMO

Effective cancer therapy can be achieved by using nano-drug delivery systems which provide a targeted drug delivery strategy by overcoming the drawbacks of conventional treatments like chemotherapy and radiation. ZnO nanoparticles are a potent anticancer agent that causes tumor cell destruction with the targeted drug delivery. In this present study, green synthesis of ZnO nanoparticles has been done using the plant Solanum nigrum. The synthesized ZnO nanoparticles were studied by the characterization techniques like UV-visible spectroscopy, SEM, TEM, DLS, zeta potential, FTIR, and XRD. The synthesized ZnO nanoparticles of Solanum nigrum exhibited a significant anticancer activity against HeLa cell lines through the apoptotic pathway. The cytotoxicity of ZnO nanoparticles was assessed using MTT assay, wound healing assay, DAPI staining, and acridine orange and ethidium bromide double staining. The expression patterns of ß-catenin, p53, caspase-3, and caspase-9 were analyzed using reverse transcriptase-PCR. The results obtained from the study indicate that the ZnO nanoparticles of Solanum nigrum possess a dose-dependent cytotoxic effect against HeLa cell lines through the inhibition of ß-catenin and increasing the levels of p53, caspase-3, and caspase-9.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Nanopartículas , Solanum nigrum , Neoplasias do Colo do Útero , Óxido de Zinco , Antibacterianos/farmacologia , Antineoplásicos/química , Apoptose , Caspase 3 , Caspase 9 , Feminino , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteína Supressora de Tumor p53 , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , beta Catenina
10.
Artigo em Inglês | MEDLINE | ID: mdl-34956401

RESUMO

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects (n = 65) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking (P < 0.05) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Fatores de Risco
11.
Asian Pac J Cancer Prev ; 22(11): 3507-3511, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837906

RESUMO

OBJECTIVE: Local chickens were spontaneously sampled and slaughtered in the central markets of Coimbatore, Erode, and Namakkal districts, South India. MATERIALS AND METHODS: Wet digestion was used to extract lead (Pb), cadmium (Cd), and zinc (Zn) in their blood and selected different organs (intestine, breast, liver, and gizzard), and their concentrations were measured using an atomic absorption spectrophotometer. RESULTS: Apart from the blood of chickens from Coimbatore and Namakkal, where Pb was not found, the concentrations of Pb in the blood and organs of chickens from the three towns ranged from 1.8 to 8.33 mg/kg, exceeding the maximum tolerance thresholds (0.1 mg/kg) in internal organs of poultry birds. Except for the intestine of chickens from the three areas, Cd was only found in the heart, blood, and gizzard of Erode chickens, as well as the liver and gizzard of Namakkal chickens, in concentrations ranging from 0.13 to 0.58. According to threshold level, the upper limit met the maximum limits (0.5 mg/kg). Zn was found in all sections of chickens from the three selected districts, with concentrations ranging from 4.96 to 174.17 mg/kg. CONCLUSION: Its concentrations were within the permissible limits (10-50 mg/kg) in some areas of certain chickens, but it surpassed the permissible limit in the liver of chicken from Coimbatore. Any organs and blood from local chickens sold in Coimbatore, Erode, and Namakkal areas can be hazardous to one's health.


Assuntos
Cádmio/análise , Contaminação de Alimentos/análise , Chumbo/análise , Produtos Avícolas/análise , Animais , Carcinógenos , Galinhas , Humanos , Índia , Concentração Máxima Permitida , Espectrofotometria Atômica
12.
Asian Pac J Cancer Prev ; 22(11): 3591-3599, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837917

RESUMO

BACKGROUND: Cooking oil fumes (COFs) with smoking habits is a substantial risk that aggravates genetic modifications. The current study was to estimate the biological markers of genetic toxicity counting Micronucleus changes (MN), Chromosome Aberrations (CA) and DNA modifications among COFs exposures and control subjects inherent from South India. MATERIALS AND METHODS: Present analysis comprised 212 COFs with tobacco users and equivalent number of control subjects. RESULTS: High frequency of CA (Chromatid type: and chromosome type) were identified in group II experimental subjects also high amount of MN and DNA damage frequency were significantly (p < 0.05) in both subjects (experimental smokers and non-smokers). Present analysis was observed absence of consciousness among the COFs exposures about the destructive level of health effects of tobacco habits in working environment. CONCLUSION: COFs exposed workers with tobacco induce the significant alteration in chromosomal level. Furthermore, a high level of rate of genetic diseases (spontaneous abortion) were identified in the experimental subjects. This finding will be helpful for preventive measures of COFs exposed workers and supportive for further molecular analysis.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Culinária , Dano ao DNA/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Óleos/toxicidade , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Estudos de Casos e Controles , Análise Citogenética , Feminino , Humanos , Índia , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Uso de Tabaco/genética
13.
Pharmacol Res ; 170: 105709, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34089868

RESUMO

Electrons exchange amongst the chemical species in an organism is a pivotal concomitant activity carried out by individual cells for basic cellular processes and continuously contribute towards the maintenance of bioenergetic networks plus physiological attributes like cell growth, phenotypic differences and nutritional adaptations. Humans exchange matter and energy via complex connections of metabolic pathways (redox reactions) amongst cells being a thermodynamically open system. Usually, these reactions are the real lifeline and driving forces of health and disease in the living entity. Many shreds of evidence support the secondary role of reactive species in the cellular process of control apoptosis and proliferation. Disrupted redox mechanisms are seen in malaises, like degenerative and metabolic disorders, cancerous cells. This review targets the importance of redox reactions in the body's normal functioning and the effects of its alterations in cells to obtain a better understanding. Understanding the redox dynamics in a pathological state can provide an opportunity for cure or diagnosis at the earlier stage and serve as an essential biomarker to predict in advance to give personalized therapy. Understanding redox metabolism can also highlight the use of naturally available antioxidant in the form of diet.


Assuntos
Antioxidantes/administração & dosagem , Dieta , Metabolismo Energético/efeitos dos fármacos , Micronutrientes/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Micronutrientes/efeitos adversos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
14.
J Gastrointest Cancer ; 52(3): 1022-1028, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33047269

RESUMO

PURPOSE: Colorectal cancer (CRC) is one of the recurring and lethal gastrointestinal tract disease rankings as the primary cause of worldwide morbidity and mortality. In general, the tumour node metastasis (TNM) and Dukes classification assist in diagnosis, prognosis and treatments of CRC along with haematological examinations and tumour demographic characterisations in patients. METHODS: The present investigation is carried out on clinically acknowledged sixty-five CRC patients based on haematological findings and are sorted into stages using TNM and Dukes. The present study is to find the association between haematological findings, demographic characters, differentiation position, lymph node invasion and tumour node metastasis in CRC patients in accordance with their age. RESULTS: We observed significant (p < 0.05) nexus between lymph node metastasis and tumour node metastasis on the basis of tumour's differentiation demographic positioning and age of the individuals. CONCLUSION: Earlier location tracing and medicinal treatment or surgery lessen the chance of CRC morbidity and mortality along with prolonging survival rate via prognostic factors and disease position determination.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Gradação de Tumores/estatística & dados numéricos , Estadiamento de Neoplasias/estatística & dados numéricos , Adulto , Idoso , Neoplasias Colorretais/sangue , Feminino , Humanos , Índia/epidemiologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
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