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1.
Biomed Mater ; 16(4): 042003, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33686970

RESUMO

Advanced biomaterials are increasingly used for numerous medical applications from the delivery of cancer-targeted therapeutics to the treatment of cardiovascular diseases. The issues of foreign body reactions induced by biomaterials must be controlled for preventing treatment failure. Therefore, it is important to assess the biocompatibility and cytotoxicity of biomaterials on cell culture systems before proceeding to in vivo studies in animal models and subsequent clinical trials. Direct use of biomaterials on animals create technical challenges and ethical issues and therefore, the use of non-animal models such as stem cell cultures could be useful for determination of their safety. However, failure to recapitulate the complex in vivo microenvironment have largely restricted stem cell cultures for testing the cytotoxicity of biomaterials. Nevertheless, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages make them an ideal candidate for in vitro screening studies. Furthermore, the application of stem cells in biomaterials screening studies may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, embryonic stem cells, adult stem cells, and induced pluripotent stem cells are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.

2.
PLoS One ; 16(2): e0245072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33534822

RESUMO

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (ß-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.


Assuntos
Epitopos/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Proteoma , Vacinas Virais/imunologia , Sequência de Aminoácidos , Sítios de Ligação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/prevenção & controle , Desenho de Fármacos , Epitopos/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Vacinas de Subunidades/química , Vacinas de Subunidades/imunologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/imunologia , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/imunologia , Vacinas Virais/química
3.
Crit Rev Eukaryot Gene Expr ; 31(1): 79-92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639058

RESUMO

Diabetic cardiomyopathy is characterized as abnormal function and structure of myocardium associated with diabetes irrespective of other cardiac risk factors like hypertension or coronary artery disease (CAD). The pathogenesis of DCM was not well understood in the past due to its complexity but it has been discovered recently. Various factors are found to be associated with the onset of DCM including impaired calcium handling, remodeling of extracellular matrix (ECM), increased oxidative stress, altered metabolism, mitochondrial dysfunction, and endothelial dysfunction. Micro-RNAs (miRNAs) are also found to be of great importance in the pathogenesis of DCM. Different miRNAs like miR-126, miR-24, miR-1, miR-155, miR-499, and miR-199a are found to be associated with different types of heart diseases like CAD and myocardial infarction. Studies have shown that the miRNA plays a crucial role in the development of DCM and it was found that the expression levels of different miRNAs differ in patients as compared to healthy individuals. This review focuses on the pathogenesis of DCM and various factors involved in the onset of diabetic car-diomyopathy. Moreover, the probable role of miRNA in the pathogenesis of DCM is also discussed.

4.
Biomed Mater ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33592587

RESUMO

Advanced biomaterials have produced a significant impact on healthcare by improving the quality of life of people with disabilities. Biomaterials are immensely used in tissue engineering, wound healing applications, and delivery of cancer targeted therapeutics. Biocompatibility and cytotoxicity screening of biomaterials on cell culture systems is the first step before their in vivo testing in animal models and subsequent clinical trials. Direct use of biomaterials on animals may create technical challenges as well as ethical concerns. In order to avoid the ethical concerns of animal use, many non-animal models such as stem cell cultures are being developed and utilized for testing their safety. However, due to several limitations including the inability to recapitulate the complex in vivo microenvironment, the application of stem cell cultures is limited. However, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages like hepatocytes, cardiomyocytes, and neural cells make them an ideal candidates for in vitro screening studies. Furthermore, the application of stem cells may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, Embryonic Stem Cells (ESCs), Adult Stem Cells (ASCs), and Induced Pluripotent Stem Cells (iPSCs) are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the current status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.

5.
Biomed Mater ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075764

RESUMO

Impaired diabetic wounds are one of the major pathophysiological complications caused by persistent microbial infections, prolonged inflammation, and insufficient angiogenic responses. Here, we report the development of nitric oxide (NO) releasing S-nitroso-N-acetyl-pencillamine (SNAP) loaded chitosan/polyvinyl alcohol hydrogel and its efficacy in enhancing wound healing potential of bone marrow mesenchymal stem cells in diabetic wounds. NO-releasing hydrogels significantly increased the cell viability and cell proliferation of hydrogen peroxide (H2O2) pretreated bone marrow stem cells (BMSCs) depicting its cytoprotective activity which was further confirmed by a manifold increase in the gene expression of B-cell lymphoma 2 (Bcl-2), stromal cell-derived factor 1alpha (SDF-1α), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). Furthermore, the SNAP loaded hydrogel showed continuous cell proliferating activity for six days due to the slow release of NO from hydrogel. Wound healing studies on diabetes-induced rabbits showed that the application of SNAP preconditioned BMSCs and NO-releasing hydrogels significantly speed up the healing process compared to the control group. The wound healing potential of BMSCs plus NO-releasing hydrogel was further validated by improved collagen deposition and epithelial layer formation by histopathological examinations as well as upregulation of VEGF and SDF-1α biomarkers through gene expression analysis. These results exhibited that the application of BMSCs and NO-releasing hydrogel can help in faster regeneration of damaged tissues. Therefore, BMSCs plus NO-releasing hydrogels can be very useful for the treatment of diabetic wounds.

6.
PLoS One ; 14(8): e0221318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31465475

RESUMO

Syzygium cumini (S. cumini) is an evergreen tropical plant that is well recognized for its therapeutic potential of common diseases. In this study, the therapeutic potential and biomedical application of S. cumini are assessed in vitro and in vivo to find its effectiveness for different complications. The methanolic crude extract of S. cumini leaves were screened for total phenolic and flavonoid content. In vitro, the DPPH scavenging assay, XTT assay, prothrombin and activated partial thromboplastin time were used to assess antioxidant, cytoprotective and thrombolytic activity of the S. cumini extract, respectively. The anti-inflammatory potential and the analgesic activity of the S. cumini extract were analyzed in rabbits by the Carrageenan induced paw edema method and the writhing method, respectively. Phytochemical analysis showed the presence of considerable amounts of total phenolic (369.75 ± 17.9 mg GAE/g) and flavonoid (75.8 ± 5.3 mgRE/g) content in the S. cumini extract. The DPPH assay demonstrated a higher antioxidant potential (IC-50 value of 133 µg/ml), which was comparable to the IC-50 of ascorbic acid (122.4 µg/ml). Moreover, the S. cumini extract showed a dose dependent cytoprotective effect against H2O2 treated bone marrow mesenchymal stem cells (BM-MSCs). S. cumini also possesses significant anticoagulant activity with a prothrombin time of 28.3 ± 1.8 seconds vs 15.8 ± 0.2 seconds of control, p<0.05. The leaf extract also demonstrated an analgesic effect in rabbits as indicated by the decrease in writhing (12.2 ± 1.7 control vs. 3.7 ± 0.6 treated) and anti-inflammatory activity in rabbits paw with a protection against inflammation of 64.1 ± 2.4%. Our findings suggest that the methanolic extract of S. cumini leaves has antioxidant, cytoprotective, anticoagulant, analgesic and anti-inflammatory properties, and therefore, can be applied for treating cardiovascular diseases and cancers.


Assuntos
Analgésicos , Anti-Inflamatórios , Antioxidantes , Edema/tratamento farmacológico , Fenóis , Extratos Vegetais , Folhas de Planta/química , Syzygium/química , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Carragenina/toxicidade , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
7.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1145-1154, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303583

RESUMO

Survivin (IAP proteins) is considered as a significant target for anticancer drug research owing to its upregulation in tumor cells to mediate resistance to apoptotic stimulus. The current study aimed to investigate phytochemicals as inhibitors of survivin with caspases to reactivate the functioning of caspases through molecular docking. The compounds namely 2(R), 4(R)-dihydroxypyrrolidine, 4-hydroxy-2-(4-methoxyphenyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide, 2,3-Diketo-L-gulonic acid, (3-hydroxy-2-octadeca-9,12-dienoyloxypropyl) octadecanoate, 2-[[4-[[4-[(4-formamido-1-methylimidazole-2-carbonyl)amino]-1-methylimidazole-2-carbonyl]amino]-1-methylimidazole-2-carbonyl]amino]ethyl-dimethylazanium, Picolinic acid and (2-Hydroxy-5-nitrophenyl) dihydrogen phosphate successfully bind inside the pocket of survivin. ADMETsar was used to evaluate the anticancer potential of selected compounds. These compounds can be proposed as effective inhibitors, disrupting the survivin-caspases interaction and reactivating the caspases function of apoptosis. The study might facilitate the development of cost-effective and natural drugs against cancer. However, further validation is essential for confirmation of its drug efficacy and bio-compatibility.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Compostos Fitoquímicos/farmacologia , Survivina/antagonistas & inibidores , Survivina/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/toxicidade , Caspases/metabolismo , Simulação por Computador , Humanos , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Compostos Fitoquímicos/farmacocinética , Compostos Fitoquímicos/toxicidade , Conformação Proteica , Survivina/metabolismo , Distribuição Tecidual
8.
Microb Pathog ; 132: 243-253, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075428

RESUMO

Ebola virus (EBOV), a non-segmented single-stranded RNA virus, is often-most transmitted through body fluids like sweat, tears, saliva, and nasal secretions. Till date, there is no licensed vaccine of EBOV is available in the market; however, the world is increasingly vulnerable to this emerging threat. Hence, it is the need of time to develop a vaccine for EBOV to hinder its dissemination. The current study has been designed for identification and characterization of the potential B and T-cell epitopes using the Immuno-informatics tools, and it helped in finding the potent vaccine candidates against EBOV. Prediction, antigenicity and allergenicity testing of predicted B and T cells' epitopes was done as well to identify their potential as a vaccine candidate and to measure their safety level respectively. Among B-cell epitopes "WIPAGIGVTGVIIA" showed a high antigenicity score and it would play an important role in evoking the immune response. In T-cell epitopes, peptides "AIGLAWIPY" and "IRGFPRCRY" presented high antigenicity score, which binds to MHC class-I and MHC class-II alleles respectively. All predicted epitopes were analyzed and compared with already reported peptides carefully. Comparatively, Peptides predicted in the present study showed more immunogenicity score than already reported peptides, used as positive control, and are more immunogenic as compared to them. Peptides reported in the present study do not target only Zaire EBOV (ZEBOV), as in previous studies, but also other species, i.e. Tai Forest EBOV (TAFV), Sudan EBOV (SUDV), Bundibugyo EBOV (BDBV), and Reston EBOV (RESTV) and would bring the promising results as potent vaccine candidates.


Assuntos
Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Glicoproteínas/imunologia , Alelos , Sequência de Aminoácidos , Vacinas contra Ebola/genética , Ebolavirus/genética , Genes MHC Classe I , Genes MHC da Classe II , Glicoproteínas/química , Glicoproteínas/genética , Antígeno HLA-B7 , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína
9.
Pak J Pharm Sci ; 32(1(Supplementary)): 345-351, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30829214

RESUMO

Chronic pain has been defined as the persistence that remained for more than three months. The extent of previous time duration with the normal time of natural healing phase becomes poor and results in reduced life quality and morbidity. Opioids are well recognized therapy for pain management and the clinical prescriptions based on opioids have been defined with increasing implicating behavior among patients suffering with chronic pain. The association between the pain and immunity has long been established since the involvement of interleukin-1ß (IL-1ß) in sickness that is considered with the induced hyperalgesia. In the context of pharmacodynamics Toll like receptors (TLRs) are involved in the negative effects of opioids as analgesics. The soluble factors released by immune cells as well as from the disruptive cells bind to TLRs. This binding leads the pre and post-synaptic ends on endothelial and microglial cells that exhibit the activation of complex inhibitory and excitatory process at the synapses site. In TLRs, TLR4 is mostly reported that is strongly associated in specifically in areas of T cells and macrophages. The current study is designed to investigate the structural insights of the opioids and TLR4 interactions by using computational approach in the aspect of recognizing the chemical combinatorial factors that are involved in the pain management. This study targets that how opioids interact with TLR4 and the process of chemical interaction that leads to negative effects of opioids at neuroimmune interface as well as to investigate the extent of particular naltrexone that mediates with the negative effects of opioids.


Assuntos
Mutação , Naltrexona/química , Naltrexona/farmacologia , Receptor 4 Toll-Like/química , Receptor 4 Toll-Like/genética , Analgésicos Opioides/química , Humanos , Morfina/química , Naltrexona/metabolismo , Antagonistas de Entorpecentes/química , Antagonistas de Entorpecentes/metabolismo , Antagonistas de Entorpecentes/farmacologia , Receptor 4 Toll-Like/metabolismo
10.
Int J Pharm ; 559: 23-36, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30668991

RESUMO

Non-healing wounds are among the serious complications of type-2-diabetes around the globe, associated with high incidence of bacterial infection, chronic nerve and blood vessel damage, and eventually repeated amputation of limbs and organs. Silver nanoparticles offer strong wound healing potential due to their well-known antibacterial activities. The present study reports the development of silver nanoparticle impregnated chitosan-poly ethylene glycol (PEG) hydrogel to accelerate wound healing in diabetic patients. The aim of the study was to formulate a sustained and slow release of silver nanoparticle using chitosan-PEG-Silver Nitrate based hydrogel for the treatment of chronic diabetic wounds. The silver nanoparticle containing chitosan-PEG pre-polymer solution was synthesized by reducing silver nitrate with PEG and chitosan solution, thereby, transforming the silver ions into silver nanoparticles. The resulted pre-polymer solution was then crosslinked using glutaraldehyde to form the desired hydrogel. The developed silver nanoparticle impregnated chitosan hydrogel was characterized using ultra-violet (UV) visible spectrophotometry, Fourier Transform-infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) followed by the determination of porosity, and swelling properties. The release of AgNPs from hydrogel was determined by UV-vis spectroscopy followed by antimicrobial and antioxidant assays. The wound healing efficacy of the synthesized hydrogel was evaluated in diabetic rabbits. The results demonstrated a higher porosity, higher degree of swelling and higher water vapor transition rate (WVTR) for silver nanoparticle impregnated hydrogel compared to bare chitosan-PEG hydrogel as well as improved antimicrobial and antioxidant properties in-vitro and enhanced wound healing capability in-vivo in diabetic rabbits. The hydrogel showed a slow and sustained release of AgNPs over a period of at least seven days manifesting the slow biodegradation of developed hydrogels. The improved antimicrobial, antioxidant and wound healing results indicate that the silver nanoparticle impregnated chitosan-PEG hydrogel can be a promising material for wound healing dressing for chronic diabetic wounds.


Assuntos
Quitosana/química , Complicações do Diabetes/tratamento farmacológico , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Materiais Biocompatíveis/química , Diabetes Mellitus , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos
11.
Crit Rev Eukaryot Gene Expr ; 28(4): 373-384, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30311586

RESUMO

The rapid development of direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) therapy dramatically altered the treatment landscape of this disease. The DAA regimen is associated with various advantages including high sustained virological response (SVR) with minimum side effects and low pill load and specific inhibition of viral replication, which lowers dependence on the host cell. This regimen has substantially replaced conventional (interferon) therapy with high cure rates (> 90%) in most HCV populations. This review provides insight into clinical studies of NS3/4A protease inhibitors, NS5B viral polymerase inhibitor (nucleotide and non-nucleotide), and NS5A inhibitors, alone and in combination.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/fisiologia , Hepatite C/tratamento farmacológico , Antivirais/farmacologia , Ensaios Clínicos como Assunto , Farmacorresistência Viral/efeitos dos fármacos , Quimioterapia Combinada , Hepacivirus/patogenicidade , Humanos , Interferons/uso terapêutico , Inibidores de Proteases/farmacologia , Ribavirina/uso terapêutico , Serina Proteases , Proteínas não Estruturais Virais/antagonistas & inibidores
12.
Crit Rev Eukaryot Gene Expr ; 27(4): 331-340, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29283327

RESUMO

Dengue is an acute infectious disease of viral etiology characterized by lymphadenopathy, leucopenia, headache, biphasic fever, pain in various parts of the body, rashes, and extreme physical weakness. It is a vector-borne disease caused by a positive-stranded RNA virus of the family Flaviviridae, genus Flavivirus. Dengue inflicts a significant health, economic, and social burden on populations of endemic areas. Dengue virus is transmitted to humans by the mosquito vector Aedes aegypti. Vaccines against dengue viruses have been claimed to be developed, but as yet no effective treatment is available. Alternative therapeutic strategies to overcome this disease and its spread are direly needed. A traditional sterile insect technique (SIT) harms the health of male insects, leading to their reduced ability to compete for wild-type female insects for breeding. Oxitec (Abingdon, UK) has developed genetically modified (GM) strains of A. aegypti via the release of insects carrying a dominant lethal (RIDL) strategy. RIDL male mosquitoes offer a resolution to many of the limitations of traditional SIT, which has resulted in reduced application of SIT in mosquitoes. The technique using RIDL mosquitoes is considered to be ecologically friendly and specific. Homing endonuclease genes, also called selfish genes, can also be used in genetic modification methods in such a way that the vector population and its competency can be reduced. GM mosquitoes carrying a gene that transcribes RNA interference can also be crucial to control expression of RNA viruses. The RNA virus interference pathway is one of the most critical components of the innate immune system of insects that can frustrate a variety of RNA viruses such as Flaviviruses. Here, we summarize and focus on alternative techniques used to control dengue spread.


Assuntos
Aedes/genética , Animais Geneticamente Modificados/genética , Dengue/genética , Animais , Dengue/virologia , Humanos , Mosquitos Vetores/genética , Interferência de RNA/fisiologia , Vírus de RNA/genética
13.
Pak J Pharm Sci ; 30(5(Supplementary)): 1965-1969, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29105629

RESUMO

Hepatitis C Virus (HCV) infection is a worldwide serious health issue which contributes towards most of the hepatic morbidities. So far no prophylaxis is available to prevent this virus; therefore, development of antiviral compounds to fight HCV infection is the need of time. Chemically synthesized peptides that are potent immunogenic antigens are being pursued as candidate vaccines against HCV. The present study was planned to identify peptide inhibitors having potential to block the activity of NS3 protein of HCV that will ultimately arrest HCV multiplication. Docking of NS3 with peptides revealed that the majority of the peptides have strong binding affinity for active sites of NS3. Peptide 1, 2, 3 and 6 were found interactive with NS3 active residues while the active sites of NS3 had hydrophobic contact with the rest of peptides. Thus, these peptides bear therapeutic potential of a candidate drug for the prevention of HCV replication. Post docking analysis revealed important binding abilities of peptides with the active sites of NS3 protein, showing the efficiency of peptides as potential peptide inhibitors against HCV. The study revealed that HCV replication can be inhibited by these peptides. HCV replication inhibition potential of these peptides can contribute in reducing the burden of HCV infection and its associated complications worldwide.


Assuntos
Antivirais/farmacologia , Desenho Assistido por Computador , Desenho de Fármacos , Hepacivirus/efeitos dos fármacos , Simulação de Acoplamento Molecular , Peptídeos Cíclicos/farmacologia , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/química , Sítios de Ligação , Domínio Catalítico , Hepacivirus/enzimologia , Hepacivirus/crescimento & desenvolvimento , Peptídeos Cíclicos/química , Inibidores de Proteases/química , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos
14.
Curr Stem Cell Res Ther ; 12(8): 611-623, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28831915

RESUMO

BACKGROUND: Diabetes mellitus, the widely prevalent disease of pancreas, is a metabolic disorder caused by autoimmune destruction of ß cells or insulin insufficiency or insulin resistance. Replacement of damaged ß cells by cell therapy can mitigate the condition and re-establish normal metabolic control. This has opened up new horizons for research, such as stem cells, cellular reprogramming and ß cell regeneration. OBJECTIVE: The goal of the study was to summarize the available literature on the use of stem cells for the regeneration of pancreatic ß cells and treatment of diabetes mellitus. RESULTS AND CONCLUSION: Stem cells are exceptional having the potential to self renew and differentiate in many lineages. Stem cells hold tremendous potential to regenerate ß cells and treat diabetes mellitus but many milestones on the way are yet to be achieved. But researchers do believe that stem cells and regenerative medicines will be widely used in clinical practices and possibly new effective methodology would be designed for even cure, mitigate and reduce the social burden of diabetes mellitus.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Diabetes Mellitus/terapia , Transplante de Células-Tronco/métodos , Animais , Reprogramação Celular , Humanos , Células Secretoras de Insulina , Medicina Regenerativa/métodos
15.
Crit Rev Eukaryot Gene Expr ; 27(1): 1-17, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28436328

RESUMO

Regenerative medicine is an emerging field to find solutions to some of the most challenging medical problems of humans. Regenerative medicine has the potential to revolutionize the whole health care system, in dealing with conditions such as heart disease, emphysema, liver fibrosis, kidney disease, diabetes, and neurological disorders. Among the many challenges to bringing regenerative medicine to the clinic is the selection of the best cell types and reliable ways to expand the number of cells. Stem cells emerged as the best cell type for regeneration of different organs. This review covers the application of stem cells in different degenerative diseases.


Assuntos
Medicina Regenerativa , Células-Tronco , Humanos
16.
Pak J Pharm Sci ; 29(6 Suppl): 2297-2302, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28167469

RESUMO

Amounts of DNA damage and homocysteine (Hcy) in heart patients blood may have strong function in the causation of cardiovascular disease (CVD). The main objective of this work was to know experimentally the role of total oxidants (produced by Reactive Oxygen species (ROS), clinical biochemical indices, their oxidized products and total antioxidant status (TAS) among such patients to find the association of homocysteine, total oxidation status (TOS) and oxidative DNA damage with other clinical parameters in sixty positive CVD patients compared with those of 60 normal subjects. As compared to healthy individuals, CVD patients had significantly higher concentrations of homocysteine (p<0.0001), total oxidants stress (TOS) (p<0.0001), serum total lipids (p<0.04), malondialdehyde (MDA) (p<0.001), high density lipoprotein-cholesterol (HDL-C) (p<0.0001), and low density lipoprotein cholesterol (LDL-C) (p<0.01), than those of healthy individuals. Plasma Hcy content, TOS and amount of DNA were positively and significantly associated with cholesterol, triglycerides, systolic blood pressure, urea, and albumin (p values<0.01). TOS, Hcy and oxidative DNA damage were negatively correlated with HDL-c, TAS and proteins. It is suggested that these parameters have pivotal role in diagnostic process of determining severity in CAD patients. Oxidized products of macromolecules in blood of CVD patients impart major functions in causing CVD disease.


Assuntos
Doenças Cardiovasculares/sangue , Dano ao DNA , Homocisteína/sangue , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Humanos , Lipídeos/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Regulação para Cima
17.
Bioinformation ; 10(7): 454-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25187687

RESUMO

Computational tools occupy the prime position in the analysis of large volume of post-genomic data. These tools have advantage over the wet lab experiments in terms of high coverage, cost and time. Breast cancer is the most common cancer in females worldwide. It is a genetically heterogeneous disorder and many genes are involved in the pathway of the disease. Mutations in metastasis suppressor gene are the major cause of the disease. In this study, the effects of mutations in breast cancer metastasis suppressor 1gene upon protein structure and function were examined by means of computational tools and information from databases.This study can be useful to predict the potential effect of every allelic variant, devise new biological experiments and to interpret and predict the patho-physiological impact of new mutations or non-synonymous polymorphisms.

18.
Viral Immunol ; 27(5): 250-4, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24811215

RESUMO

Hepatitis C virus (HCV) is a dreadful viral disease, responsible for 170 million cases worldwide, of which most are from Asia and Africa and approximately 10 million people are from Pakistan. Currently, the pegylated interferon alpha (PEG-INF-α) has been approved as the standard of care in combination with ribavirin and Boceprevir/Telaprevir. Many studies regarding gene expression analysis of liver biopsy samples of patients with chronic HCV infection have been carried out previously. However, there are very few reports of expression analysis carried out using blood samples of HCV patients. Therefore, in this study, gene expression of human immune responsive genes (MMP-9, OAS1) and fibrogenic responsive gene (KRT19) was done in the peripheral blood mononuclear cells (PBMCs) of chronic HCV infected patients having differences in viral titers. Blood samples were collected from different hospitals in Pakistan. RNA was extracted and cDNA was synthesized according to the protocol prescribed by the Enzynomics™ M-MLV Reverse Transcriptase(®) Kit. The synthesized cDNA was amplified through polymerase chain reaction (PCR) using specific primers of immune responsive genes. The results were further evaluated using real-time PCR. There was a significant increase in the expression of the immune responsive genes (MMP-9, OAS1, CXCL6, CXCR3, ApoA1, and MYC) of HCV genotype 3a patients compared to controls. Similarly, the expression of the fibrosis genes was upregulated in HCV genotype 3a patients compared to controls. The information gained through this study is helpful to identify a noninvasive marker to determine liver fibrosis, and may also give useful information to understand HCV pathogenesis and develop better therapeutic regimens.


Assuntos
Perfilação da Expressão Gênica , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Cirrose Hepática/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Hepacivirus/isolamento & purificação , Hospitais , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Paquistão , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Adulto Jovem
19.
Bioinformation ; 9(19): 978-82, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24391361

RESUMO

Hepatitis C is serious health concern worldwide caused by HCV. It causes liver cirrhosis and hepato-cellular carcinoma. Development of prevention solutions is under progress. Meanwhile, the treatment of the viral disease using compounds isolated from natural medicinal plants is promising. The traditional use of photo-chemicals from medicinal plants like Amelanchier alnifolia for viral treatment is hopeful. Therefore, it is of interest to screen for flavonoids from Amelanchier alnifolia against protein targets of HCV. Hence, we assessed the binding of flavonoids to HCV NS3/4A protease and helicase proteins. Results show that Quercitin 3- galactoside and 3-glucosideshowed good binding score with protease and helicase respectively. Their interaction/binding sites are documented in this report. This data provide insights for the consideration of flavonoids as potential inhibitors of HCV/NS3/4A protease and helicase.

20.
Bioinformation ; 9(20): 1031-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24497731

RESUMO

Diabetes Mellitus is affecting people of all age groups worldwide. Many synthetic medicines available for type 2 diabetes mellitus in the market. However, there is a strong requirement for the development of better anti-diabetes compounds sourced especially from natural sources like medicinal plants. The extracts from the leaves of neem (Azadirachta indica) is traditionally known to have anti-diabetes properties. Therefore, there is an increased interest to identify potential compounds identified from neem leaf extracts showing predicted binding property with the known diabetes mellitus type 2 protein enzyme target phosphoenol-pyruvate carboxykinase(PEPCK). The structure data for compounds found in the leaf extract of neem was screened against PEPCK using molecular docking simulation and screening techniques. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses best binding properties with PEPCK. This observation finds application for further consideration in in vitro and in vivo validation.

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