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Diabetes is known to increase susceptibility to hypertension due to increase in inflammation, oxidative stress, and endothelial dysfunction, leading to vascular stiffness. The polytherapy might lead to several drug-drug interactions (DDIs), which cause certain life-threatening complications such as diabetic nephropathy and hypoglycaemia. So, in this review we focused on drug-drug interactions and impact of genetic factors on drug responses for better disease management. Drug-drug interactions (DDIs) may act either synergistically or antagonistically. For instance, a combination of metformin with angiotensin II receptor antagonist or angiotensin-converting enzyme inhibitors (ACEIs) synergistically improves glucose absorption, whereas the same hypertensive drug combination with sulphonylurea might cause severe hypoglycaemia sometimes. Thiazolidinediones (TDZs) can cause fluid retention and heart failure when taken alone, but a combination of angiotensin II receptor antagonist with TZDs prevents these side effects. Interindividual genetic variation affects the DDI response. We found two prominent genes, GLUT4 and PPAR-γ, which are common targets for most of the drug. So, all of these findings established a connection between drug-drug interaction and genetics, which might be used for effective disease management.
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Diabetes Mellitus , Hipertensão , Hipoglicemia , Humanos , Farmacogenética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Antagonistas de Receptores de Angiotensina/efeitos adversosRESUMO
Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.
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COVID-19 , Interleucina-6 , Humanos , Interleucina-6/genética , Predisposição Genética para Doença , COVID-19/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Frequência do GeneRESUMO
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1-/- , GSTT1-/- and GSTM1-/- /GSTT1-/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1-/- genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1-/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1-/- genotype showed higher mortality.
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COVID-19/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético , SARS-CoV-2/patogenicidade , Adulto , Idoso , Alelos , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Feminino , Seguimentos , Expressão Gênica , Frequência do Gene , Glutationa/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Modelos de Riscos Proporcionais , Índice de Gravidade de DoençaRESUMO
Osteoarthritis (OA) is a chronic degenerative and musculoskeletal disorder. The toxicity associated with nonsteroidal antiinflammatory drugs (NSAIDs) limits its use in the management of OA. To ameliorate these toxicities, natural antioxidants can be used as substitutes for the management of OA. Therefore, this study is aimed to investigate the prophylactic mechanisms of Punica granatum L. peel (PGP) in collagenase-induced OA rat compared with indomethacin. OA was induced in female Sprague Dawley rats by intraarticular injection of collagenase type-II and treated with PGP (250 and 500 mg/kg body wt) and a positive control (PC) indomethacin (3 mg/kg body wt). The results demonstrated that PGP reduced the collagenase induced OA as compared with indomethacin treated group through reducing blood ALP (P < .001) and significantly (P < .001) inhibited cartilage erosion as indicated in histological slides with retention of collagen and proteoglycan content. Quantitative real-time PCR analysis revealed the considerable (P < .05) upregulation in the expression of COL-2 gene and downregulation of MMP-3 and COX-2 genes in the PGP treated group. The high phenolic content (633 ± 1.16 mg/GAE) and flavonoid content (420.3 ± 2.14 mg/RE) contribute to the strong antioxidant activity with IC50 value (320 ± 2.2 µg/mL) of DPPH free radical scavenging activity. These results need further validation in clinical studies and thus, PGP could be developed as a preventive drug treatment for OA.
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PURPOSE: To evaluate visual field (VF) progression and rate of glaucomatous VF loss in patients with primary angle-closure glaucoma (PACG) using pointwise linear regression (PLR) trend analysis. DESIGN: Clinic-based retrospective study. PARTICIPANTS: Primary angle-closure glaucoma patients with 5 or more reliable VF tests and with 5 years or more of follow-up. METHODS: Visual field progression was assessed by PROGRESSOR software version 3.7 (Medisoft, Leeds, United Kingdom) and was defined by the presence of at least 2 adjacent testing points located within the same hemifield that showed progression with a change of -1 dB/year or more (P < 0.01) for inner points or -2 dB/year or more (P < 0.01) for edge points. We also performed a logistic regression analysis to determine the variables associated with rapid progression (defined as mean slope of progressing points ≥-1.5 dB/year). MAIN OUTCOME MEASURES: Visual field progression and rate of VF loss. RESULTS: Of the 1296 patients who were assessed, 398 (30.7%) fulfilled the inclusion criteria of 5 or more VFs and 5 years or more of follow-up. Visual field progression was observed in 63 of 398 eyes (15.8%) according to the PLR criteria. The overall mean rate of VF change for these patients was -0.12±0.51 dB/year over a mean follow-up period of 10.4±3.7 years. There were no significant differences in the age, gender distribution, follow-up duration, or number of VFs between those who showed progression and those who did not (all P > 0.05). The most common sector of VF progression was the superior arcuate area (65%). Rapid progression was found in 36 patients (57%). Multiple logistic regression analysis revealed older age and higher vertical cup-to-disc ratio (VCDR) at presentation as predictors of rapid progression (all P < 0.005) in the progressing group (n = 63). CONCLUSIONS: In patients with PACG being managed in a hospital setting, VF progression was noted in 15.8%, and the overall rate of VF loss was -0.12±0.51 dB/year. The superior arcuate was the most common sector of progression. Older age and higher VCDR at presentation were associated with rapid progression.
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Glaucoma de Ângulo Aberto/fisiopatologia , Escotoma/diagnóstico , Campos Visuais/fisiologia , Progressão da Doença , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escotoma/etiologia , Escotoma/fisiopatologia , Fatores de Tempo , Testes de Campo Visual/métodosRESUMO
IMPORTANCE: The evaluation of anterior chamber scan of Cirrus optical coherence tomography for routine clinical use. BACKGROUND: To assess the variability of anterior chamber angle measurements. DESIGN: This was a cross-sectional study. PARTICIPANTS: Forty subjects aged 40-80 years were included. METHODS: One randomly selected eye from 40 subjects was imaged with Cirrus optical coherence tomography (Carl Zeiss Meditec, Dublin, CA) by two different operators (expert vs. non-expert) with a 15-min interval for inter-observer and intra-observer variability of image acquisition. For image grading, the angle opening distance (AOD750) and the trabecular iris space area (TISA750) of nasal and temporal quadrants were measured with a customized algorithm (ImageJ, NIH, Bethesda, MD) by two different graders in a masked and random fashion. Bland Altman analysis and intraclass correlation coefficient (ICC) were calculated. MAIN OUTCOME MEASURES: ICC and limit of agreements (LOA). RESULTS: There were 15 (37.5%) eyes with closed angles. For inter-observer variability, the mean difference (95% LOA) of AOD750 for image acquisition and grading were -0.0039 mm (-0.0486, 0.0408) and 0.0011 mm (-0.0228, 0.025), respectively. The mean difference (95% LOA) of AOD750 for intra-observer variability for image acquisition and grading were 0.0013 mm (-0.0362, 0.0389) and -0.0013 mm (-0.0482, 0.0457), respectively. The ICCs were all ≥0.9. There was no significant difference in measurement variability between open and closed angles (P > 0.05). CONCLUSIONS AND RELEVANCE: Anterior chamber scan had low inter-observer and intra-observer variability in quantitative evaluation that was not affected by the angle status or the experience of an operator.
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Algoritmos , Câmara Anterior/diagnóstico por imagem , Glaucoma/diagnóstico , Processamento de Imagem Assistida por Computador , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos TestesRESUMO
Curcuma longa L., commonly known as turmeric, is one of the economically and medicinally important plant species. It is predominantly cultivated in the tropical and sub tropical countries. India is the largest producer, and exporter of turmeric in the world, followed by China, Indonesia, Bangladesh and Thailand. In the present study, Directed Amplification of Minisatellite DNA (DAMD) and Inter Simple Sequence Repeats (ISSR), methods were used to estimate the genetic variability in indigenous turmeric germplasm. Cumulative data analysis for DAMD (15) and ISSR (13) markers resulted into 478 fragments, out of which 392 fragments were polymorphic, revealing 82 % polymorphism across the turmeric genotypes. Wide range of pairwise genetic distances (0.03-0.59) across the genotypes revealed that these genotypes are genetically quite diverse. The UPGMA dendrogram generated using cumulative data showed significant relationships amongst the genotypes. All 29 genotypes studied grouped into two clusters irrespective of their geographical affiliations with 100 % bootstrap value except few genotypes, suggesting considerable diversity amongst the genotypes. These results suggested that the current collection of turmeric genotypes preserve the vast majority of natural variations. The results further demonstrate the efficiency and reliability of DAMD and ISSR markers in determining the genetic diversity and relationships among the indigenous turmeric germplasm. DAMD and ISSR profiling have identified diverse turmeric genotypes, which could be further utilized in various genetic improvement programmes including conventional as well as marker assisted breeding towards development of new and desirable turmeric genotypes.
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Niosomes are newly developed, self-assembling sac-like transporters that deliver medication at a specific site in a focused manner, increasing availability in the body and prolonging healing effects. Niosome discovery has increased drugs' therapeutic effectiveness while also reducing adverse effects. This article aims to concentrate on the increase in the worldwide utilization of niosomal formulation. This overview presents a thorough perspective of niosomal investigation up until now, encompassing categories and production techniques, their significance in pharmaceutical transportation, and cosmetic use. The thorough literature review revealed that extensive attention has been given to developing nanocarriers for drug delivery as they hold immense endeavor to attain targeted delivery to the affected area simultaneously shielding the adjacent healthy tissue. Many reviews and research papers have been published that demonstrate the interest of scientists in niosomes. Phytoconstituents, which possess antioxidant, antibiotic, anti-inflammatory, wound healing, anti-acne, and skin whitening properties, are also encapsulated into niosome. Their flexibility allows for the incorporation of various therapeutic agents, including small molecules, proteins, and peptides making them adaptable for different types of drugs. Niosomes can be modified with ligands, enhancing their targeting capabilities. A flexible drug delivery mechanism provided by non-ionic vesicles, which are self-assembling vesicular nano-carriers created from hydrating non-ionic surfactant, cholesterol, or amphiphilic compounds along comprehensive applications such as transdermal and brain-targeted delivery.
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This paper provides an outline of the Human immunodeficiency virus (HIV), its mechanism of action, and types of HIV/AIDS. Additionally, it offers recent advances and patent data on HIV medications and formulations for the last ten years. The HIV/AIDS patents describes how compounds can stop viruses from spreading and stop HIV from multiplying. It also gives information about monolithic tablets, fixed oral doses of triple HIV formulations, and drug delivery systems that use electrospun fibers. The patents also reveals the treatment for patients having liver disease by using herbal ingredients. The effects of various herbal ingredients and preparations on HIV replication, immunological function, and symptom management have been researched. Despite the encouraging randomized trial data available, it is crucial to proceed cautiously when using herbal treatments for HIV/AIDS treatment. Recent years clinical trials of HIV/AIDS were also reviewed. Herbal remedies are preferred more than other drugs because they have fewer side effects and have long-lasting effects for the treatment of HIV/AIDS. The regulation, quality assurance, and standardization of herbal products are the challenges for the industry.
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Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Humanos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Sistemas de Liberação de MedicamentosRESUMO
Using skin patches to deliver drugs is dependable and doesn't have the same issues as permeation enhancers, which help drugs get through the skin but struggle because of the skin's natural barrier. Strategies are required to increase topical bioavailability to enhance drug absorption. Natural compounds offer a promising solution by temporarily reducing skin barrier resistance and improving drug absorption. Natural substances allow a wider variety of medications to be distributed through the stratum corneum, offering a dependable approach to enhancing transdermal drug delivery. Natural substances have distinct advantages as permeability enhancers. They are pharmacologically effective and safe, inactive, non-allergenic, and non-irritating. These characteristics ensure their suitability for use without causing adverse effects. Natural compounds are readily available and well tolerated by the body. Studies investigating the structure-activity relationship of natural chemicals have demonstrated significant enhancer effects. By understanding the connection between chemical composition and enhancer activity, researchers can identify effective natural compounds for improving drug penetration. In conclusion, current research focuses on utilizing natural compounds as permeability enhancers in transdermal therapy systems. These substances offer safety, non-toxicity, pharmacological inactivity, and non-irritation. Through structure-activity relationship investigations, promising advancements have been made in enhancing drug delivery. Using natural compounds holds enormous potential for improving the penetration of trans-dermally delivered medications.
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Administração Cutânea , Sistemas de Liberação de Medicamentos , Permeabilidade , Absorção Cutânea , Humanos , Absorção Cutânea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Permeabilidade/efeitos dos fármacos , Animais , Pele/metabolismo , Pele/efeitos dos fármacos , Preparações de Plantas/administração & dosagem , Preparações de Plantas/farmacologia , Preparações de Plantas/química , Relação Estrutura-Atividade , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Produtos Biológicos/farmacologiaRESUMO
The intricate ecosystem of microorganisms residing within and on the human body, collectively known as the microbiome, significantly influences human health. Imbalances in this microbiome, referred to as dysbiosis, have been associated with various diseases, prompting the exploration of novel therapeutic approaches. Personalized medicine, Tailors treatments to individual patient characteristics, offers a promising avenue for addressing microbiome-related health issues. This review highlights recent developments in utilizing personalized medicine to target the microbiome, aiming to enhance health outcomes. Noteworthy strategies include fecal microbiota transplantation (FMT), where healthy donor microbes are transferred to patients, showing promise in treating conditions such as recurrent Clostridium difficile infection. Additionally, probiotics, which are live microorganisms similar to beneficial gut inhabitants, and prebiotics, non-digestible compounds promoting microbial growth, are emerging as tools to restore microbiome balance. The integration of these approaches, known as synbiotics, enhances microbial colonization and therapeutic effects. Advances in metagenomics and sequencing technologies provide the means to understand individual microbiome profiles, enabling tailored interventions. This paper aims to present the latest insights in leveraging personalized medicine to address microbiome-related health concerns, envisioning a future where microbiome-based therapies reshape disease management and promote human health.
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Diabetes has become a pandemic as the number of diabetic people continues to rise globally. Being a heterogeneous disease, it has different manifestations and associated complications in different individuals like diabetic nephropathy, neuropathy, retinopathy, and others. With the advent of science and technology, this era desperately requires increasing the pace of embracing precision medicine and tailoring of drug treatment based on the genetic composition of individuals. It has been previously established that response to antidiabetic drugs, like biguanides, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and others, depending on variations in their transporter genes, metabolizing genes, genes involved in their action, etc . Responsiveness of these drugs also relies on epigenetic factors, including histone modifications, miRNAs, and DNA methylation, as well as environmental factors and the lifestyle of an individual. For precision medicine to make its way into clinical procedures and come into execution, all these factors must be reckoned with. This review provides an insight into several factors oscillating around the idea of precision medicine in type-2 diabetes mellitus.
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Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.
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BACKGROUND: Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents. OBJECTIVE: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. METHODS: Cell viability was analyzed in HeLa cells at different concentrations (25-300 µg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK. RESULTS: Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski's Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. CONCLUSION: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.
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Antineoplásicos Fitogênicos/farmacologia , Cissus/química , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologiaRESUMO
Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.
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Substituição de Aminoácidos , COVID-19/epidemiologia , COVID-19/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Polimorfismo Genético , SARS-CoV-2/patogenicidade , Adulto , Fatores Etários , Idoso , Alelos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Doenças Assintomáticas , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Diabetes Mellitus , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Interações Hospedeiro-Patógeno/genética , Humanos , Hipertensão , Índia/epidemiologia , Isoleucina/genética , Isoleucina/metabolismo , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
Human papillomaviruses (HPV) infection is a major causative agent and strongly associated with the development of cervical cancer. Understanding the mechanisms of HPV-induced cervical cancer is extremely useful in therapeutic strategies for primary prevention (HPV vaccines) and secondary prevention (screening and diagnosis of precancerous lesions). However, due to the lack of proper implementation of screening programs in developing countries, cervical cancer is usually diagnosed at advanced stages that result in poor treatment responses. Nearly half of the patients will experience disease recurrence within two years post treatment. Therefore, it is vital to identify new tools for early diagnosis, prognosis, and treatment prediction. MicroRNAs (miRNAs) are small non-coding RNAs, implicated in posttranscriptional regulation of gene expression. Growing evidence has shown that abnormal miRNA expression is associated with cervical cancer progression, metastasis, and influences treatment outcomes. In this review, we provide comprehensive information about miRNA and their potential utility in cervical cancer diagnosis, prognosis, and clinical management to improve patient outcomes.
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MicroRNAs/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/etiologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , MicroRNAs/administração & dosagem , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , PrognósticoRESUMO
PURPOSE: To compare the distribution of plateau iris in eyes across varying severity of primary angle closure glaucoma (PACG) using standardized ultrasound biomicroscopy (UBM) criteria. DESIGN: Cross-sectional study. METHODS: UBM was performed on 210 patients with PACG who had previously undergone laser peripheral iridotomy. Plateau iris was defined as the presence of all the following UBM criteria in ≥2 quadrants of the angle: anteriorly directed ciliary body, absent ciliary sulcus, iris angulation, flat iris plane, and iridotrabecular contact. Disease severity was based on the visual field mean deviation (MD) and classified as early-to-moderate (MD ≥ -12 dB), advanced (-12.01 dB to -20 dB), and severe (MD < -20 dB). RESULTS: Of 210 subjects recruited, 23 were excluded because of poor quality UBM images. The remaining 187 patients were categorized as having early-to-moderate (n = 103), advanced (n = 38), and severe PACG (n = 46). Of these subjects, 48.1% were male, and 90.9% were of Chinese ethnicity. The overall proportion of plateau iris was 36.9%, with 32.0% (33/103) in early-to-moderate, 34.2% (13/38) in advanced, and 50% (23/46) in severe PACG (P = .03, comparing severe PACG with early-to-moderate groups). Among the severe PACG group, those with plateau iris configuration had significantly smaller anterior chamber area (P = .03) and volume (P = .01) compared with those without plateau iris. CONCLUSION: The higher proportion of plateau iris configuration in eyes with severe PACG compared with early-to-moderate PACG suggest that this may be a contributory factor for disease severity.
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Glaucoma de Ângulo Fechado/complicações , Pressão Intraocular/fisiologia , Iridectomia/métodos , Doenças da Íris/etiologia , Iris/diagnóstico por imagem , Terapia a Laser/métodos , Campos Visuais/fisiologia , Idoso , Estudos Transversais , Feminino , Seguimentos , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/cirurgia , Gonioscopia , Humanos , Iris/cirurgia , Doenças da Íris/diagnóstico , Doenças da Íris/cirurgia , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: The collective impact of climate change and soil salinity is continuously increasing the degraded lands across the globe, bringing agricultural productivity and food security under stress. The high concentration of salts in saline soils impose osmotic, ionic, oxidative and water stress in plants. Biological solutions can be the most reliable and sustainable approach to ensure food security and limit the use of agro-chemicals. AIM OF REVIEW: Halo-tolerant plant growth promoting rhizobacteria (HT-PGPR) are emerging as efficient biological tools to mitigate the toxic effects of high salt concentrations and improve the growth of plants, simultaneously remediating the degraded saline soils. The review explains the role of HT-PGPR in mitigating the salinity stress in plants through diverse mechanisms and concurrently leading to improvement of soil quality. KEY SCIENTIFIC CONCEPTS OF REVIEW: HT-PGPR are involved in alleviating the salinity stress in plants through a number of mechanisms evoking multipronged physiological, biochemical and molecular responses. These include changes in expression of defense-related proteins, exopolysaccharides synthesis, activation of antioxidant machinery, accumulation of osmolytes, maintaining the Na+ kinetics and improving the levels of phytohormones and nutrient uptake in plants. The modification of signaling by HT-PGPR inoculation under stress conditions elicits induced systemic resistance in plants which further prepares them against salinity stress. The role of microbial-mechanisms in remediating the saline soil through structural and compositional improvements is also important. Development of novel bioinoculants for saline soils based on the concepts presented in the review can be a sustainable approach in improving productivity of affected agro-ecosystems and simultaneously remediating them.
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There are two long-standing theories about the pathogenesis of glaucoma - barotrauma and the effect of vascular hypoxia. Currently, it is still unknown whether diminished blood flow is the cause or result of glaucomatous atrophy of ganglion cells and the optic nerve. Though many other imaging techniques used to directly assess ocular blood flow have been well studied, they are limited by their inability to directly assess metabolism in the ocular tissues or measure the oxygen carrying capacity in the vessels. Retinal oximetry is a relatively novel, noninvasive imaging technique that reliably measures oxygen saturation levels in the retinal vessels, offering surrogate markers for the metabolic demands of the eye. The clinical significance of these measurements has not been well established. Thus, this review gives an overview of ocular imaging and current retinal oximetry techniques, while contextualizing the important oximetry studies that have investigated the vascular theory behind glaucoma.
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OBJECTIVE: To identify the mechanisms of angle closure in the fellow eyes of Vietnamese subjects with unilateral primary angle-closure glaucoma (PACG) using ultrasound biomicroscopy (UBM) before and after prophylactic laser peripheral iridotomy (LPI). DESIGN: This is a prospective observational study. PARTICIPANTS: Patients diagnosed with PACG in one eye and primary angle-closure suspect (PACS) in the other eye were included in this study, conducted from January 2014 to October 2014 at Vietnam National Institute of Ophthalmology. MATERIALS AND METHODS: A total of 112 PACS fellow eyes of 112 patients presenting with unilateral PACG were evaluated. All subjects underwent standard ophthalmic clinical examination and UBM imaging a week before and after LPI. On the basis of UBM images, the angle-closure mechanism was defined according to the classification of Svend Vedel Kessing and John Thygesen as pupillary block (PB), plateau iris (PI), and mixed pattern. RESULTS: The proportion of PACS subjects who showed PB was 86.6%, while 13.4% showed a PI configuration before LPI. After LPI the pre-LPI PB group was reclassified, with 55.4% showing pure PB, and 31.3% showing mixed mechanisms (PB and PI). The proportion of patients with PI remained unchanged (13.4%) even after LPI. After the LPI, the angle opening significantly increased in the PB subgroup (14.01±2.43 degrees, P<0.01) and reclassified mixed group (6.34±1.71 degrees, P<0.01) but remained almost unchanged in the PI group (1.81±0.98 degrees, P>0.05). CONCLUSION: On the basis of the UBM criteria, PI was found in 13.4% of PACS fellow eyes of Vietnamese subjects with PACG. The clinical and UBM features of patients showing PI before LPI remained almost unchanged after the procedure. The proportion of patients showing PB pre-LPI reduced from 86.6% to 55.4% showing the important role of mixed mechanisms in PACG.