Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
Environ Pollut ; 346: 123588, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401635

RESUMO

Environmental contamination is aninsistent concern affecting human health and the ecosystem. Wastewater, containing heavy metals from industrial activities, significantly contributes to escalating water pollution. These metals can bioaccumulate in food chains, posing health risks even at low concentrations. Copper (Cu), an essential micronutrient, becomes toxic at high levels. Activities like mining and fungicide use have led to Copper contamination in soil, water, and sediment beyond safe levels. Copper widely used in industries, demands restraint of heavy metal ion release into wastewater for ecosystem ultrafiltration, membrane filtration, nanofiltration, and reverse osmosis, combat heavy metal pollution, with emphasis on copper.Physical and chemical approaches are efficient, large-scale feasibility may have drawbackssuch as they are costly, result in the production of sludge. In contrast, bioremediation, microbial intervention offers eco-friendly solutions for copper-contaminated soil. Bacteria and fungi facilitate these bioremediation avenues as cost-effective alternatives. This review article emphasizes on physical, chemical, and biological methods for removal of copper from the wastewater as well asdetailing microorganism's mechanisms to mobilize or immobilize copper in wastewater and soil.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Humanos , Cobre/análise , Ecossistema , Águas Residuárias , Poluentes do Solo/análise , Metais Pesados/toxicidade , Solo , Biodegradação Ambiental
2.
Explor Target Antitumor Ther ; 4(5): 850-895, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970206

RESUMO

Despite consistent progress in prompt diagnosis and curative therapies in the last decade, lung cancer (LC) continues to threaten mankind, accounting for nearly twice the casualties compared to prostate, breast, and other cancers. Statistics associate ~25% of 2021 cancer-related deaths with LC, more than 80% of which are explicitly caused by tobacco smoking. Prevailing as small and non-small cell pathologies, with respective occurring frequency of nearly 15% and 80-85%, non-small cell LCs (NSCLCs) are prominently distinguished into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes. Since the first use of epidermal growth factor receptor (EGFR) inhibitor gefitinib for NSCLC treatment in 2002, immense progress has been made for targeted therapies with the next generation of drugs spanning across the chronological generations of small molecule inhibitors. The last two years have overseen the clinical approval of more than 10 therapeutic agents as first-line NSCLC medications. However, uncertain mutational aberrations as well as systemic resistant responses, and abysmal overall survival curtail the combating efficacies. Of late, immune checkpoint inhibitors (ICIs) against various molecules including programmed cell death-1 (PD-1) and its ligand (PD-L1) have been demonstrated as reliable LC treatment targets. Keeping these aspects in mind, this review article discusses the success of NSCLC chemo and immunotherapies with their characteristic effectiveness and future perspectives.

3.
Pharmacol Rep ; 75(4): 817-837, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37354313

RESUMO

The earliest documented COVID-19 case caused by the SARS-CoV-2 coronavirus occurred in Wuhan, China, in December 2019. Since then, several SARS-CoV-2 mutants have rapidly disseminated as exemplified by the community spread of the recent omicron variant. The disease already attained a pandemic status with ever-dwindling mortality even after two and half years of identification and considerable vaccination. Aspergillosis, candidiasis, cryptococcosis and mucormycosis are the prominent fungal infections experienced by the majority of SARS-CoV-2 high-risk patients. In its entirety, COVID-19's nexus with these fungal infections may worsen the intricacies in the already beleaguered high-risk patients, making this a topic of substantial clinical concern. Thus, thorough knowledge of the subject is necessary. This article focuses on the concomitant fungal infection(s) in COVID-19 patients, taking into account their underlying causes, the screening methods, manifested drug resistance, and long-term effects. The information and knowledge shared herein could be crucial for the management of critically ill, aged, and immunocompromised SARS-CoV-2 patients who have had secondary fungal infections (SFIs).


Assuntos
COVID-19 , Micoses , Humanos , Idoso , SARS-CoV-2 , COVID-19/complicações , Micoses/diagnóstico , Micoses/terapia , Pandemias
4.
Curr Top Med Chem ; 23(15): 1395-1413, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36597609

RESUMO

Prevalent as a major phenolic ingredient of soy and soy products, genistein is recognized as an eminent phytoestrogen owing to its interacting ability with estrogen receptors (ERs). The metabolic conversion of plant-derived genistin to genistein by gut microbes and intestinal enzymes enhances its absorption at intestinal pH of ~7.5-7.8. Genistein interferes in breast cancer (BC) development via pleiotropic actions on cell proliferation, survival, angiogenesis, and apoptosis. Though multiple investigations have demonstrated genistein intake-driven reduced BC risk, similar efficacy has not been replicated in clinical trials. Furthermore, multiple studies have structurally and functionally equated genistein extents with 17-ß-estradiol (E2), the most available physiological estrogen in females, culminating in aggravated BC growth. Of note, both genistein and E2 function via interacting with ERs (ERα and ERß). However, although E2 shows almost equal affinity towards both ERα and ERß, genistein shows more affinity towards ERß than ERα. Our cautious literature survey revealed typical intake mode, ER expression pattern and the ratio of ERα and ERß, transactivators/ regulators of ERα and ERß expression and activities, patient age, and menopausal status as decisive factors affecting genistein BC activities. Of further interest are the mechanisms by which genistein inhibits triple-negative breast cancers (TNBCs), which lack ERs, progesterone receptors (PRs), and human epidermal growth factor receptors (HER2). Herein, we attempt to understand the dosage-specific genistein actions in BC cells and patients with an insight into its better response via derivative development, nanocarrier-assisted, and combinatorial delivery with chemotherapeutic drugs.


Assuntos
Neoplasias da Mama , Genisteína , Feminino , Humanos , Genisteína/farmacologia , Fitoestrógenos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Disponibilidade Biológica
5.
Pharmaceutics ; 15(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36678856

RESUMO

Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with consequent invasion and metastasis. Treatment with CDs is indeed well-versed but it is badly curtailed with accompanying side effects and inadequacies of site-specific drug delivery. As a result, drug carriers ensuring stealth delivery and sustained drug release with improved pharmacokinetics and biodistribution are urgently needed. Core-shell mesoporous silica nanoparticles (MSNPs) have recently been a cornerstone in this context, attributed to their high surface area, low density, robust functionalization, high drug loading capacity, size-shape-controlled functioning, and homogeneous shell architecture, enabling stealth drug delivery. Recent interest in using MSNPs as drug delivery vehicles has been due to their functionalization and size-shape-driven versatilities. With such insights, this article focuses on the preparation methods and drug delivery mechanisms of MSNPs, before discussing their emerging utility in BC treatment. The information compiled herein could consolidate the database for using inorganic nanoparticles (NPs) as BC drug delivery vehicles in terms of design, application and resolving post-therapy complications.

6.
Curr Pharm Des ; 29(37): 2954-2976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38173051

RESUMO

BACKGROUND: In the plant kingdom, flavonoids are widely distributed with multifunctional immunomodulatory actions. Hesperetin (HST) remains one of the well-studied compounds in this domain, initially perceived in citrus plants as an aglycone derivative of hesperidin (HDN). OBSERVATIONS: Natural origin, low in vivo toxicity, and pleiotropic functional essence are the foremost fascinations for HST use as an anticancer drug. However, low aqueous solubility accompanied with a prompt degradation by intestinal and hepatocellular enzymes impairs HST physiological absorption. MOTIVATION: Remedies attempted herein comprise the synthesis of derivatives and nanocarrier (NC)-mediated delivery. As the derivative synthesis aggravates the structural complexity, NC-driven HST delivery has emerged as a sustainable approach for its sustained release. Recent interest in HST has been due to its significant anticancer potential, characterized via inhibited cell division (proliferation), new blood vessel formation (angiogenesis), forceful occupation of neighboring cell's space (invasion), migration to erstwhile physiological locations (metastasis) and apoptotic induction. The sensitization of chemotherapeutic drugs (CDs) by HST is driven via stoichiometrically regulated synergistic actions. Purpose and Conclusion: This article sheds light on HST structure-function correlation and pleiotropic anticancer mechanisms, in unaided and NC-administered delivery in singular and with CDs synergy. The discussion could streamline the HST usefulness and long-term anticancer efficacy.


Assuntos
Hesperidina , Humanos , Hesperidina/farmacologia , Hesperidina/química , Flavonoides , Antioxidantes/farmacologia
7.
Toxicol Rep ; 9: 1614-1623, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561961

RESUMO

Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical.

8.
Mol Biol Rep ; 49(12): 11491-11502, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36097111

RESUMO

Out of all the cancer types, the most prevalent one is lung cancer. Multiple genes and signaling pathways play role in the progression of lung cancer. Considering the wider prevalence and fatality of lung cancer it has become the focus of current cancer research. Though currently used approaches have shown positive results against lung cancer but success against non-small cell lung cancer (NSCLC) still looms as an enigma for the entire research fraternity. The development of resistance against inhibitors within a short span is one of the reasons responsible for the failure and relapse of lung cancer. Under these prevailing conditions genome/gene-editing technology using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR associated proteins (Cas), popularly known as CRISPR/Cas technology offers a convenient and flexible method for inducing precise changes within the lung cancer cell. Additionally, CRISPR-barcoding and CRISPR knockout screens at the genome-wide level can help in the functional investigation of specific mutations and identification of novel cancer drivers respectively. Several variants of the CRISPR/Cas system are being developed to limit off-targeting with enhanced precision. The present review article updates the usefulness of CRISPR/Cas technology against various types of lung cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Sistemas CRISPR-Cas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Tecnologia
9.
Mol Biol Rep ; 49(7): 7101-7110, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35568789

RESUMO

BACKGROUND: The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system was initially identified in bacteria and archaea as a defense mechanism to confer immunity against phages. Later on, it was developed as a gene editing tool for both prokaryotic and eukaryotic cells including plant cells. METHODS AND RESULTS: CRISPR/Cas9 approach has wider applications in reverse genetics as well as in crop improvement. Various characters involved in enhancing economic value and crop sustainability against biotic/abiotic stresses can be targeted through this tool. Currently, CRISPR/Cas9 gene editing mechanism has been applied on around 20 crop species for improvement in several traits including yield enhancement and resistance against biotic and abiotic stresses. In the last five years, maximum genome editing research has been validated in rice, wheat, maize and soybean. Genes targeted in these plants has been involved in causing male sterility, conferring resistance against pathogens or having certain nutritional value. CONCLUSIONS: Current review summarizes various applications of CRISPR/Cas system and its future prospects in plant biotechnology targeting crop improvement with higher yield, disease tolerance and enhanced nutritional value.


Assuntos
Sistemas CRISPR-Cas , Produtos Agrícolas , Biotecnologia , Sistemas CRISPR-Cas/genética , Produtos Agrícolas/genética , Genoma de Planta , Valor Nutritivo , Plantas Geneticamente Modificadas/genética
10.
COPD ; 18(6): 737-748, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34615424

RESUMO

Chronic obstructive pulmonary disease (COPD) is a slowly progressive and poorly reversible airway obstruction disease. It is caused either alone or in combination of emphysema, chronic bronchitis (CB), and small airways disease. COPD is thought to be a multi-factorial disorder in which genetic susceptibility, environmental factors and tobacco exposure could be doubly or simultaneously implicated. Available medicines against COPD include anti-inflammatory drugs, such as ß2-agonists and anticholinergics, which efficiently reduce airflow limitation but are unable to avert disease progression and mortality. Advanced glycation end products (AGE) and their receptors i.e. receptor for advanced glycation end products (RAGE) are some molecules that have been implicated in the complication of COPD. Several RAGE single nucleotide polymorphic (SNP) variants are produced by the mammalian cells. Based on the ethnicity some SNPs aggravate the COPD severity. Mammalian cells produce several alternative RAGE splice variants including a soluble RAGE (sRAGE) and an endogenous soluble RAGE (esRAGE). Both of these act as decoy receptor and thus may help to arrest the COPD complications. Several lines of evidences indicate a decreased level of sRAGE in the COPD subjects. One of the new strategies to reduce COPD complication may be sRAGE therapeutic administration to the COPD subjects. This comprehensive discussion sheds light on the role of RAGE and its polymorphic variants in the COPD complication along with sRAGE therapeutic significance in the COPD prevention.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Receptor para Produtos Finais de Glicação Avançada , Animais , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Pulmão , Mamíferos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/uso terapêutico
11.
Cancers (Basel) ; 14(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35008242

RESUMO

Non-small cell lung cancers (NSCLCs) account for ~85% of lung cancer cases worldwide. Mammalian lungs are exposed to both endogenous and exogenous estrogens. The expression of estrogen receptors (ERs) in lung cancer cells has evoked the necessity to evaluate the role of estrogens in the disease progression. Estrogens, specifically 17ß-estradiol, promote maturation of several tissue types including lungs. Recent epidemiologic data indicate that women have a higher risk of lung adenocarcinoma, a type of NSCLC, when compared to men, independent of smoking status. Besides ERs, pulmonary tissues both in healthy physiology and in NSCLCs also express G-protein-coupled ERs (GPERs), epidermal growth factor receptor (EGFRs), estrogen-related receptors (ERRs) and orphan nuclear receptors. Premenopausal females between the ages of 15 and 50 years synthesize a large contingent of estrogens and are at a greater risk of developing NSCLCs. Estrogen-ER/GPER/EGFR/ERR-mediated activation of various cell signaling molecules regulates NSCLC cell proliferation, survival and apoptosis. This article sheds light on the most recent achievements in the elucidation of sequential biochemical events in estrogen-activated cell signaling pathways involved in NSCLC severity with insight into the mechanism of regulation by ERs/GPERs/EGFRs/ERRs. It further discusses the success of anti-estrogen therapies against NSCLCs.

12.
Curr Med Res Opin ; 37(2): 207-217, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33306409

RESUMO

INTRODUCTION: In December 2019, the first COVID-19 case, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported in Wuhan, China. The SARS-CoV-2 rapidly disseminated throughout the world via community spread, acquiring pandemic status with significant fatality. OBSERVATIONS: Rapid SARS-CoV-2 diagnosis was soon perceived critical for arresting community spread and effective therapy development. Human SARS-CoV-2 infection can be diagnosed either by nucleic acid identification or specific antibody detection. Contrary to nucleic acid identification confirmed active SARS-CoV-2 infection; antibody detection confirms a past infection, even in asymptomatic subjects. SARS-CoV-2 specific antibodies augment the ability to effectively counter the virus. A crucial hurdle limiting the steadfast implementation of antibody detection is the time required for threshold B lymphocyte population generation. This process is dependent on precise antigen recognition and MHC class I molecules presentation. CONCLUSIONS: Thus, nucleic acid and antibody dependent tests complement each other in identifying human SARS-CoV-2 infection and shaping up subsequent immunological responses. This article discusses the complimentary association of nucleic acid identification (corresponding to an active infection) and antibody testing (the yester CoV-2 infection vulnerability) as the diagnostic and screening measures of SARS-CoV-2 infection. Highlights Nucleic acid (RNA) identification and specific antibody detection against SARS-CoV-2 are the noted diagnostic mechanisms for screening human SARS-CoV-2 infection. While nucleic acid identification screens prevailing SARS-CoV-2 infection, detection of SARS-CoV-2 specific antibodies signifies a past infection, even in asymptomatic subjects. Antibodies against SARS-CoV-2 provide a potential therapeutic option via transfer from antibody rich plasma of a recovered subject to an infected individual. Nucleic acid identification may not absolutely confirm the infection because of frequent SARS-CoV-2 genome mutations and possible technical errors, while specific antibody detection also needs at least (8-14) days for detectable screening of B-cell generated antibodies. Nucleic acid and antibody tests are complementary to each other as an early stage diagnostic assay for SARS-CoV-2 infection and possible therapy (antibodies). Sufferers with a high clinical suspicion but negative RT-PCR screening could be examined via combined imaging and repeated swab test.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/imunologia , Teste para COVID-19 , Aprovação de Teste para Diagnóstico , Ensaio de Imunoadsorção Enzimática , Humanos , Medições Luminescentes , Programas de Rastreamento , Testes de Neutralização , Pandemias , RNA Viral/isolamento & purificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia
13.
Eur Heart J Suppl ; 21(Suppl D): D59-D62, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31043880

RESUMO

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. A recently conducted study on 1.3 million adults in India showed the prevalence of hypertension to be 25.3%. Raised BP is responsible for 8.5% of the total Disability Adjusted Life Years and is also an important contributor to cardiovascular disease which is the leading cause of deaths in the country. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. The study was conducted in over 500 screening sites across the country and involved over 5000 volunteers. Screening sites included health facilities such as hospitals and clinics, as well as a variety of public spaces. A total of 240 376 individuals were screened during MMM17. Out of the 122 685 screenees for whom all three BP readings were available, 38 974 (31.8%) had hypertension based on the mean of second and third reading. Of individuals not receiving antihypertensive medication, 21 679 (17.7%) were hypertensive. Of individuals receiving antihypertensive medication, 14 203 (82.6%) had uncontrolled BP. MMM17 was the largest collaborative BP screening campaign undertaken in India with involvement of the public as well as the private sector. Over two-thirds of the individuals on antihypertensive treatment had uncontrolled BP. Approximately one-fifth of the participants had raised BP and were not on antihypertensive treatment prior to the study. These results suggest that opportunistic screening can identify significant numbers with raised BP.

14.
Curr Drug Targets ; 20(6): 679-689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30457049

RESUMO

The receptor for advanced glycation end products (RAGE) is a multi-ligand pattern recognition receptor that is highly expressed in lung epithelial cells. It helps alveolar epithelial cells to maintain their morphology and specific architecture. However, in various pathophysiological conditions, pulmonary tissues express a supraphysiological level of RAGE and its ligands including advanced glycation end products, high mobility group box 1 proteins, and S100 proteins. On interaction with RAGE, these ligands stimulate downstream signaling that generates inflammation and oxidative stress leading to asthma, chronic obstructive pulmonary disease, lung cancers, idiopathic pulmonary fibrosis, acute lung injury, pneumonia, bronchopulmonary dysplasia, cystic fibrosis, and sepsis. Thus, pharmacological agents that can either suppress the production of RAGE or block its biological activity would offer promising therapeutic value against pathogenesis of the aforementioned lungassociated diseases. This review presents a comprehensive overview of the recent progress made in defining the functions of RAGE in lung-associated diseases.


Assuntos
Antígenos de Neoplasias/metabolismo , Pneumopatias/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Proteína HMGB1/metabolismo , Humanos , Ligantes , Pneumopatias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Terapia de Alvo Molecular , Ligação Proteica/efeitos dos fármacos , Proteínas S100/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
15.
Mol Biol Rep ; 45(6): 1647-1652, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30121821

RESUMO

Human serum albumin (HSA) is a major plasma protein and binding of drugs with this plasma protein has a great importance. It possess esterase activity which can cleave the drugs containing ester bond and thus, can regulate the effect of drugs. Till date no systematic study has been done to analyse binding of such drugs and to compare the results with the drugs which do not have ester bond. Therefore, in the present study two different categories-ester and non-ester drugs have been considered to analyse their interaction with HSA at two principle drug binding sites using molecular modelling tools. It is observed that the drugs irrespective of ester or non-ester nature prefer either Sudlow site I or II by hydrogen bond and hydrophobic interactions. The information obtained from the study can assist to study pharmacokinetics of the drugs and that in turn will help in noval drug discoveries.


Assuntos
Simulação de Acoplamento Molecular/métodos , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Sítios de Ligação/efeitos dos fármacos , Esterases/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Ligação Proteica/efeitos dos fármacos , Termodinâmica
16.
Cell Oncol (Dordr) ; 40(3): 199-208, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28534212

RESUMO

BACKGROUND: Breast cancer is a notable cause of cancer-related death in women worldwide. Metastasis to distant organs is responsible for ~90% of this death. Breast cells convert to malignant cancer cells after acquiring the capacity of invasion/intravasation into surrounding tissues and, finally, extravasation/metastasis to distant organs (i.e., lymph nodes, lungs, bone, brain). Metastasis to distant organs depends on interactions between disseminated tumor cells (DTCs) and the endothelium of blood vessels present in the tumor microenvironment. Among several known endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) has been found to be involved in this process. It has been shown that VCAM-1 is aberrantly expressed in breast cancer cells and that it can bind to its natural ligand α4ß1integrin, also denoted as very late antigen 4 (VLA-4). This binding appears to be responsible for the metastasis of breast cancer cells to lung, bone and brain. The α4ß1 integrin - VCAM-1 interaction thus represents a potential therapeutic target for metastatic breast cancer cells. The development of inhibitors of this interaction may be instrumental for the clinical management of breast cancer patients. CONCLUSIONS: This study focuses on recent progress on the role of VCAM-1, an important glycoprotein belonging to the immunoglobulin (Ig) superfamily of cell surface adhesion molecules in breast cancer angiogenesis, survival and metastasis. Targeting VCAM-1, expressed on the surface of breast cancer cells, and/or its specific ligand VLA-4/α4ß1 integrin, expressed on cells at the site of metastasis, may be a useful strategy to reduce breast cancer cell invasion and metastasis. Various approaches to therapeutically target VCAM-1 and VLA-4 are also discussed.


Assuntos
Neoplasias da Mama/patologia , Invasividade Neoplásica/patologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Feminino , Humanos , Metástase Neoplásica
17.
J Mol Model ; 22(11): 267, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27761743

RESUMO

Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells. Immunogenicity of the oligopeptide can be further intensified by its simultaneous binding to the programmed death receptor of the T lymphocytes. We have used the molecular dynamics (MD) simulation approach to reveal the dynamics of the decapeptide and its consequences to immunogenic effects. The dynamics have ensembled various conformations of the peptide which have been clustered in their representative conformers. During the dynamics, the peptide was found to fold to its conformation with a minimum free energy. Moreover, multiple analysis of the MD trajectory has provided many physiochemical features involved in the biological activity to improve the immunogenicity of this antigenic peptide. The manuscript concludes by proposing this decapeptide as a potential vaccine for the melanoma cancer.


Assuntos
Imunoterapia , Melanoma , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Oligopeptídeos/química , Oligopeptídeos/uso terapêutico , Estrutura Secundária de Proteína
18.
Indian Heart J ; 68(3): 286-94, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27316479

RESUMO

BACKGROUND: Slum dwellers have poor socio-environmental conditions and less access to medical care, which make them susceptible to illnesses. Studies on urban slums have primarily focused on communicable diseases and less on lifestyle diseases, such as hypertension. Consequently, there is a paucity of prevalence studies of hypertension in slums in different parts of the country. The aim of the study was to provide estimates of the prevalence, awareness, and control of hypertension in an adult population sample of the slums of Kolkata. METHODS: A population-based cross-sectional study was conducted in the slums of Kolkata in collaboration with Kolkata Municipality Corporation. Door-to-door survey was conducted by trained healthcare workers using a structured questionnaire. Age, sex, religion, housing conditions (house/hut), average monthly household income, education status, current use of tobacco, history of hypertension, and whether on antihypertensive treatment were recorded. Blood pressure (BP) was recorded as per standard guidelines. Hypertension was diagnosed by JNC-VII criteria. A total of 10,175 adults aged ≥20 years were enrolled in the study. RESULTS: Overall prevalence of hypertension was 42%. Hypertension was newly detected in 19% of the population. Fifty-four percent of the hypertensive subjects were aware of their hypertension status, 38% were on antihypertensive treatment, and 12% had their BP controlled to target level. Subgroup analysis showed that the prevalence of hypertension was higher in men, above 60 years age, in the minority community, in those with a higher household income, and among the tobacco users. CONCLUSION: There is a high prevalence of hypertension in the slums of Kolkata. Although the awareness of the condition is high, the control of hypertension is poor.


Assuntos
Anti-Hipertensivos/uso terapêutico , Conscientização , Pressão Sanguínea/fisiologia , Hipertensão/epidemiologia , Vigilância da População/métodos , Áreas de Pobreza , População Urbana , Adulto , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
19.
J Nanobiotechnology ; 14: 26, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-27044333

RESUMO

BACKGROUND: Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine-α,ß-dehydrophenylalanine (FΔF), arginine-α,ß-dehydrophenylalanine (RΔF), valine-α,ß-dehydrophenylalanine (VΔF) and methonine-α,ß-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. RESULTS: FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC50, 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC50, 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nanoparticles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells. CONCLUSION: This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an enhancement in its efficacy as an antimalarial agent.


Assuntos
Antimaláricos/farmacologia , Curcumina/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Malária/tratamento farmacológico , Nanopartículas/administração & dosagem , Animais , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Nanotubos de Peptídeos , Plasmodium falciparum/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...