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BACKGROUND: Red blood cells (RBCs) are usually considered simple cells and transporters of gases to tissues. HYPOTHESIS: However, recent research has suggested that RBCs may have diagnostic potential in major neurodegenerative disorders (NDDs). RESULTS: This review summarizes the current knowledge on changes in RBC in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other NDDs. It discusses the deposition of neuronal proteins like amyloid-ß, tau, and α-synuclein, polyamines, changes in the proteins of RBCs like band-3, membrane transporter proteins, heat shock proteins, oxidative stress biomarkers, and altered metabolic pathways in RBCs during neurodegeneration. It also highlights the comparison of RBC diagnostic markers to other in-market diagnoses and discusses the challenges in utilizing RBCs as diagnostic tools, such as the need for standardized protocols and further validation studies. SIGNIFICANCE STATEMENT: The evidence suggests that RBCs have diagnostic potential in neurodegenerative disorders, and this study can pave the foundation for further research which may lead to the development of novel diagnostic approaches and treatments.
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Biomarcadores , Eritrócitos , Doenças Neurodegenerativas , Humanos , Eritrócitos/metabolismo , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/sangue , Biomarcadores/metabolismo , Biomarcadores/sangue , Estresse Oxidativo , Animais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/sangueRESUMO
The role of messenger RNA (mRNA) in biological systems is extremely versatile. However, it's extremely short half-life poses a fundamental restriction on its application. Moreover, the translation efficiency of mRNA is also limited. On the contrary, circular RNAs, also known as circRNAs, are a common and stable form of RNA found in eukaryotic cells. These molecules are synthesized via back-splicing. Both synthetic circRNAs and certain endogenous circRNAs have the potential to encode proteins, hence suggesting the potential of circRNA as a gene expression machinery. Herein, we aim to summarize all engineering aspects that allow exogenous circular RNA (circRNA) to prolong the time that proteins are expressed from full-length RNA signals. This review presents a systematic engineering approach that have been devised to efficiently assemble circRNAs and evaluate several aspects that have an impact on protein production derived from. We have also reviewed how optimization of the key components of circRNAs, including the topology of vector, 5' and 3' untranslated sections, entrance site of the internal ribosome, and engineered aptamers could be efficiently impacting the translation machinery for molecular and metabolic reprogramming. Collectively, molecular and metabolic reprogramming present a novel way of regulating distinctive cellular features, for instance growth traits to neoplastic cells, and offer new possibilities for therapeutic inventions.
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RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Animais , Biossíntese de Proteínas , Reprogramação MetabólicaRESUMO
The mostly aggressive and extremely malignant type of central nervous system is Glioblastoma (GBM), which is characterized by an extremely short average survival time of lesser than 16 months. The primary cause of this phenomenon can be attributed to the extensively altered genome of GBM, which is characterized by the dysregulation of numerous critical signaling pathways and epigenetics regulations associated with proliferation, cellular growth, survival, and apoptosis. In light of this, different genetic alterations in critical signaling pathways and various epigenetics regulation mechanisms are associated with GBM and identified as distinguishing markers. Such GBM prognostic alterations are identified in PI3K/AKT, p53, RTK, RAS, RB, STAT3 and ZIP4 signaling pathways, metabolic pathway (IDH1/2), as well as alterations in epigenetic regulation genes (MGMT, CDKN2A-p16INK4aCDKN2B-p15INK4b). The exploration of innovative diagnostic and therapeutic approaches that specifically target these pathways is utmost importance to enhance the future medication for GBM. This study provides a comprehensive overview of dysregulated epigenetic mechanisms and signaling pathways due to mutations, methylation, and copy number alterations of in critical genes in GBM with prevalence and emphasizing their significance.
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CONTEXT: Every year, approximately 0.4 million women suffer from endometrial cancer (EC) worldwide and it has become the most common gynecological malignancy. Almost 66% of EC cases are diagnosed at an early stage and can be cured by performing surgery while those at an advanced stage turns out to be fatal. Biomarkers of endometrial cancer would be very valuable for screening of women who are at high risk and in detecting the chance of recurrence of disease. OBJECTIVE: The current article has reviewed studies published on expression of biomarkers and susceptibility to EC. METHODS: Google Scholar and PubMed were used as searching platforms and we have majorly considered the literature from last 10 years. RESULTS: Potential biomarkers of EC identified from various studies were summarised.
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Neoplasias do Endométrio , Feminino , Humanos , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Biomarcadores , Biomarcadores TumoraisRESUMO
Polyphenols are the known group of phytochemicals that essentially consists of phenolic rings. These are the plant product present in varied fruits and vegetables. These secondary metabolites perform a protective function in plants from environmental and biological stress. When consumed as a human diet these are also known to prevent various age-associated diseases. Polyphenols are known to possess antioxidant properties and protect against oxidative stress. The literature survey was carried out using databases such as PubMed, Science direct and Springer. The research articles from last 10-12 years were selected for this review based on its relevancy with the topic. The articles selected was mainly focused on quercetin and its health benefits. The present review highlights the main functions of a flavonoid, quercetin. Quercetin is among the widely occurring polyphenol, found abundantly in nature. It is commonly present in different plant products. Onion is known to have the highest quantity of quercetin. This plant compound is possessed antioxidant properties and is considered to have a protective function against aging. It is known to be present in both free and conjugated forms. Quercetin has anti-oxidative, anti-inflammatory, anti-proliferative, anti-carcinogenic, anti-diabetic, and anti-viral properties. The molecule is lipophilic and can easily cross the BBB (Blood-Brain Barrier) and hence protects from neurodegenerative diseases. Various in vivo and in vitro studies have demonstrated the role of quercetin and here a detailed review of quercetin as a curative agent in neurodegeneration, diabetes, cancer, and inflammation has been carried out. Studies have proved that quercetin plays a crucial role in the prevention of age-related disorders. Quercetin is a potent antioxidant which is currently being used in various pharmaceuticals. Properties of quercetin can be further explored in various other disorders. Nanoformulations and liposomal formulations of quercetin can be made to treat other age associated diseases.
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Antioxidantes , Quercetina , Envelhecimento , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Flavonoides , Humanos , Polifenóis , Quercetina/química , Quercetina/farmacologia , Quercetina/uso terapêuticoRESUMO
Increasing interest has recently focused on determining whether quercetin may exert anti-aging properties or not? The objective of this study was determination of Na+, K+ -ATPase activity in quercetin-treated red blood cells during human aging. The study was carried out on human blood samples. The subjects were divided into different age groups, young, middle, and old. The effects of quercetin were evaluated by determining Na+, K+ -ATPase activity by co-incubating the red blood cells in presence of quercetin (10-6 M to 10-3 M final concentration). Quercetin causes 15% increase in Na+, K+ -ATPase activity at 10-4 M and 17% at 10-3 M as compared to the young control age group. The effect was insignificant at 10-5 M (7%) and 10-6 M (5%) in the young age group. Quercetin showed significant increase at 10-6 M to 10-3 M in Na+, K+ -ATPase activity as compared to the middle control age group. A significant increase in Na+, K+ -ATPase activity was observed at all concentrations [10-6 M (31%), 10-5 M (39%), 10-4 M (51%), and 10-3 M (61%)] in elderly population. We believe that these findings will help in further research against oxidative stress in red blood cells.
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Envelhecimento , Membrana Eritrocítica , Adenosina Trifosfatases/metabolismo , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Humanos , Íons , Proteínas de Membrana Transportadoras , Quercetina/farmacologia , SódioRESUMO
Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).
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Terapia Genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/terapia , Biomarcadores , Edição de Genes , HumanosRESUMO
Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
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Portadores de Fármacos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Doenças Respiratórias/tratamento farmacológico , Animais , HumanosRESUMO
This study aimed to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the expression of neuritin 1 (NRN1) in women with ovarian endometriosis. We collected tissues and serum from women with endometriosis treated with (n = 45) or without (n = 37) GnRHa. NRN1 mRNA and protein levels were measured using qPCR and Western blot. Immunolocalization of NRN1 in endometriotic tissues was examined using immunohistochemistry. In addition, a follow-up study was carried out to monitor the serum level of NRN1 in patients before and after GnRHa treatment. Both mRNA (p = 0.046) and protein (p = 0.0155) levels of NRN1 were significantly lower in endometriotic tissues from patients receiving GnRHa treatment compared to the untreated group. Both epithelial and stromal cells of endometriotic tissues from untreated women with endometriosis exhibited stronger staining of NRN1 but not in those who were treated with GnRHa. The follow-up study showed that the serum level of the NRN1 concentration decreased significantly from 1149 ± 192.3 to 379.2 ± 80.16 pg/mL after GnRHa treatment (p = 0.0098). The expression of NRN1 was significantly lower in women with ovarian endometriosis treated with GnRHa. These results suggest that NRN1 may be a biomarker response to the effect of GnRHa treatment for patients with ovarian endometriosis.
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Endometriose/etiologia , Endometriose/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Neuropeptídeos/genética , Ovário/patologia , Adulto , Biomarcadores , Biópsia , Endometriose/tratamento farmacológico , Endometriose/patologia , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Neuropeptídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
Red blood cells (RBCs) have emerged as biomarkers of the aging process as they undergo several changes in human aging and age-related diseases. The objectives of our study are to explore the effect of human aging on RBC indices, the strengths, therapeutic interventions, challenges, and future directions for using RBCs as a biomarker. Two online databases, PubMed and ScienceDirect, were used to search relevant studies using "RBCs as biomarkers of human aging," "red blood cells [MeSH Terms] AND biomarkers [MeSH Terms] AND human aging [MeSH Terms]," and "erythrocytes and human aging" as keywords. A total of 474 studies were identified, and after the removal of duplicates, excluding studies based on title, abstract, or full text, 74 studies and 48 additional studies found through cross-referencing were included in this systematic review. Based on the evidence, we concluded that RBC indices such as hemoglobin concentration, mean corpuscular volume, RBC distribution width, RBC membrane, oxidative stress, and metabolism change with human aging. Several studies have applied therapeutic interventions to RBCs, including dietary supplementation, phytochemicals, nanoparticles, and physical activity, to mitigate aging and related outcomes. Hence, the quality of life for older people and healthy aging can be improved by further investigating the RBC parameters, molecular mechanisms, and their implications for age-related health consequences.
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Envelhecimento , Biomarcadores , Índices de Eritrócitos , Eritrócitos , Humanos , Envelhecimento/sangue , Envelhecimento/fisiologia , Biomarcadores/sangue , Eritrócitos/metabolismo , Estresse Oxidativo/fisiologiaRESUMO
Erythrocytes undergo several changes during human aging and age-related diseases and, thus, have been studied as biomarkers of the aging process. The present study aimed to explore the antioxidant ability of metal and metal oxide nanoparticles (NPs) such as iron oxide (Fe3O4), gold (Au), and silver (Ag) to mitigate age-related oxidative stress in human erythrocytes. Metal and metal oxide NPs behave like antioxidative enzymes, directly influencing redox pathways and thus have better efficiency. Additionally, biopolymer coatings such as dextran enhance the biocompatibility of these NPs. Therefore, dextran-coated Fe3O4, Au, and Ag NPs were synthesized using wet chemical methods and were characterized. Their hemocompatibility and ability to protect erythrocytes from age-induced oxidative stress were investigated. The Fe3O4 and Au NPs were observed to protect erythrocytes from hydrogen peroxide and age-induced oxidative damage, including decreased antioxidant levels, reduced activity of antioxidative enzymes, and increased amounts of oxidative species. Pre-treatment with NPs preserved the morphology and membrane integrity of the erythrocyte. However, Ag NPs induced oxidative stress in erythrocytes similar to hydrogen peroxide. Therefore, dextran-coated Fe3O4 and Au nanoparticles have the potential to be employed as antioxidant therapies against age-related oxidative stress.
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INTRODUCTION: Human epidemiological studies have shown that diets rich in plant polyphenols have beneficial effects on various diseases including cancer. Epigallocatechin Gallate, a flavonoid polyphenol molecule, has been shown to be both chemotherapeutic and chemo-preventive in the treatment of several forms of cancer, including lung cancer. 80% of cancers of the lungs are non-small cell lung cancers. OBJECTIVE: The study was carried out to see the effects of Epigallocatechin Gallate in non-small cell lung cancer cells (A549) using in-vitro studies. MATERIALS AND METHODS: Cell Viability Assay was performed using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Wound Healing assay was also performed at different concentrations of the compound. Dexamethasone and Doxorubicin, the drugs with anti-cancer properties served as control. A549 cell lines were used. RESULTS: In the current study, it was demonstrated using Cell viability assay and Wound Healing assay that Epigallocatechin gallate exhibits anti-proliferative activity on A549 lung cancer cells and inhibits cancer cell proliferation in a concentration and time-dependent manner. It was observed that Epigallocatechin gallate (P = 0.0016, P = 0.0018) could significantly inhibit the growth of lung cancer cells with IC50 values 60.55 ± 1.0 µM. The result of wound Healing assay suggests that Epigallocatechin gallate can inhibit the proliferation and migration of A549 cells with concentrations near or higher to 50 µM. CONCLUSION: Epigallocatechin gallate's protective effect has been shown in A549 lung adenocarcinoma cells in a time and dose-dependent manner. This suggests the implication of Epigallocatechin gallate for the prevention and therapy for lung cancer.
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Endometriosis is an estrogen-dependent chronic inflammatory disorder involving the placement and growth of endometrial tissue outside the uterine cavity. It is the most common multifactorial disease that affects the life quality of women in reproductive age. Due to its multicomponent nature, early diagnosis of the disease is challenging. Since many genetic, epigenetic alterations and non-genetic factors contribute to the pathology of endometriosis, devising a drug therapy that directly acts on the ectopic tissue is extremely difficult. Endometriosis is a hormone-driven disease with estrogen considered as a primary driver for the development of endometriotic lesions. This study aims to identify biosignatures involved in endometriosis with and without gonadotropin releasing hormone agonists (GnRHa). GnRHa is a short peptide analog of GnRH that causes inhibition of estrogen and androgen synthesis. Microarray based-gene expression profiling was performed on total RNA extracted from endometriotic tissue samples with and without GnRHa-treated patients already published in our previous paper. The untreated group were considered as the control. Genes were then selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR analysis confirmed significant downregulation in(p < 0.05) expression of DARC (p = 0.0042), CDH1 (p = 0.0027), CDH5 (p = 0.0283), ATP2A3 (p < 0.001), RGS5 (p = 0.0032), and CD36 (p = 0.0162) in endometriosis patients treated with GnRHa analogs. Although, CTNNAL1 (p = 0.0136) also showed significant results but there was upregulation in their expression levels after GnRHa treatment. Thus, an altered expression of these genes makes them a possible candidate determinant of endometriosis treated with GnRHa.
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Endometriose , Humanos , Feminino , Endometriose/genética , Endometriose/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/uso terapêutico , Útero/patologia , Perfilação da Expressão Gênica , EstrogêniosRESUMO
The therapeutic application of flavonoids in the management of infectious diseases, cancers, chronic wounds, aging, and neurodegenerative disorders has been well documented in scientific literature. The citric flavonoid naringenin comes under the category of flavanone and exhibits a plethora of health benefits. Very few flavonoids such as curcumin, resveratrol, catechin, quercetin, and kaempferol have been studied to exert their anti-aging properties in humans. The effect of naringenin in the context of age-associated disorders in detail has not been elucidated yet. The databases used for the literature search were Science Direct, Google Scholar, and PubMed. More emphasis has been put on the recent literature on "naringenin" and its effect on "age-associated disorders." Almost all chronic degenerative disorders are characterized by oxidative stress and inflammatory response. The study aims at highlighting the reactive oxygen species-mediated activity of naringenin and the underlying molecular mechanism leading to the prevention of various age-associated disorders. Altogether, the review presents a systematic comprehension of the pharmaceutical and clinicopathological benefits of naringenin in age-associated disorders.
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Flavanonas , Humanos , Espécies Reativas de Oxigênio , Flavanonas/farmacologia , Flavonoides , EnvelhecimentoRESUMO
Nutraceuticals are products that provide both nutritional and therapeutic benefits. These compounds can slow the aging process and provide physiological effects shielding individuals from acute and chronic diseases. People's interests have shifted from allopathic to Ayurvedic to nutraceuticals in recent years. These are often common dietary supplements that have drawn customers worldwide because of their high nutritional safety and lack of adverse effects when used for a long time. Although conventional dosage forms, including pills, tablets, and semi-solids, are still available, they nevertheless have poorer bioavailability, less stability, and less effectiveness for targeted delivery of bioactives. The use of effective nanocomplex systems as nano-antioxidants using nanotechnology has become a promising field. Among its many uses, nanotechnology is mostly used to create foods and nutraceuticals that are more bioavailable, less toxic, and more sustainable. Additionally, it has been emphasized how precisely nano-pharmaceuticals for oxidative stress produce the desired effects. These improvements show improved antioxidant delivery to the target region, reduced leakage, and increased targeting precision. The outcomes demonstrated that oxidative stress-related illnesses can be effectively treated by lowering ROS levels with the use of nanonutraceuticals. The major ideas and uses of nano-nutraceuticals for health are outlined in this review, with an emphasis on reducing oxidative stress.
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Antioxidantes , Suplementos Nutricionais , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas/química , Nanotecnologia , AnimaisRESUMO
Cancer, being the most formidable ailment, has had a profound impact on the human health. The disease is primarily associated with genetic mutations that impact oncogenes and tumor suppressor genes (TSGs). Recently, growing evidence have shown that X-linked TSGs have specific role in cancer progression and metastasis as well. Interestingly, our genome harbors around substantial portion of genes that function as tumor suppressors, and the X chromosome alone harbors a considerable number of TSGs. The scenario becomes even more compelling as X-linked TSGs are adaptive to key epigenetic processes such as X chromosome inactivation. Therefore, delineating the new paradigm related to X-linked TSGs, for instance, their crosstalk with autosome and involvement in cancer initiation, progression, and metastasis becomes utmost importance. Considering this, herein, we present a comprehensive discussion of X-linked TSG dysregulation in various cancers as a consequence of genetic variations and epigenetic alterations. In addition, the dynamic role of X-linked TSGs in sex chromosome-autosome crosstalk in cancer genome remodeling is being explored thoroughly. Besides, the functional roles of ncRNAs, role of X-linked TSG in immunomodulation and in gender-based cancer disparities has also been highlighted. Overall, the focal idea of the present article is to recapitulate the findings on X-linked TSG regulation in the cancer landscape and to redefine their role toward improving cancer treatment strategies.
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We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed through the set parameters of pharmacokinetics (most important nonblood-brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) which most other phytoconstituents failed to pass combined with docking with EGFR protein which is highly upregulated in the colorectal carcinoma cell. The structure of 7-acetylhorminone was confirmed by single crystal X-ray diffraction studies and 1H NMR, 13C NMR, and COSY studies. To validate the theoretical studies, first, in vitro experiments were carried out against human colorectal carcinoma cell lines (HCT116) which revealed the potent cytotoxic efficacy of 7-acetylhorminone and verified preliminary investigation. Second, the drugability of 7-acetylhorminone interaction with serum albumin proteins (HSA and BSA) is evaluated both theoretically and experimentally via steady-state fluorescence spectroscopic studies, circular dichroism, isothermal titration calorimetry, and molecular docking. In summary, this study reveals the applicability of 7-acetylhorminone as a potent drug candidate or as a combinatorial drug against colorectal cancer.
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Neoplasias Colorretais , Soroalbumina Bovina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Soroalbumina Bovina/metabolismo , Soroalbumina Bovina/química , Ensaios de Seleção de Medicamentos Antitumorais , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Estrutura Molecular , Teste de Materiais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Células HCT116 , Proliferação de Células/efeitos dos fármacos , Simulação de Acoplamento Molecular , Sobrevivência Celular/efeitos dos fármacos , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismoRESUMO
OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).
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Antipsicóticos , Esquizofrenia , Adulto , Humanos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Análise Custo-Benefício , Índia , Farmacogenética , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genéticaRESUMO
This Scientometric study aimed to provide state-of-the-art information on research growth and trends, areas of potential growth and development in genomics in India, and identify the key players (organizations or institutions, and funding agencies). It was found that the number of publications and citations related to genomics research has been steadily increasing over the years, indicating a growing interest and investment in the field as the Indian Council of Agricultural Research was the leading contributor to the field. Among the 159 contributing countries from 2012 to 2021, India contributed 4.46% of publications. The Department of Biotechnology (Ministry of Science and Technology, India) provided the most funds for genomics research. In the last decade, research was primarily focused on "Genetic Diversity," "Polymorphism," "Comparative Genomics," "Phylogeny," " Random amplification of polymorphic DNA (RAPD)," "Single nucleotide polymorphism (SNP)," "Polymerase chain reaction (PCR)," "Gene Expression," etc. The study's findings may shed light on the strengths and weaknesses of the country's research infrastructure, as well as the effectiveness of government policies and funding mechanisms.
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Biotecnologia , Técnica de Amplificação ao Acaso de DNA Polimórfico , Índia , FilogeniaRESUMO
In recent years, exploring the potential of miRNAs as novel diagnostic, prognostic and diagnostic markers have gained much attention. In current study, we conducted an in-depth circRNA-miRNA-mRNA interactome to reveal significant molecular processes and biological pathways putatively associated with endometrial cancer (EC). Firstly, we retrieved two circRNAs from circad, hsa_circ_0002577 & hsa_circ_0109046, based on their association with the EC. Subsequently, we predicted miRNAs sponging sites in the two circRNAs and the potential target mRNAs of the predicted miRNAs. Sequestered miRNAs target a number of oncogenes (CBL, MET, KRAS), tumor suppressor (CFT R), receptor protein kinases & GT Pase (MET, KRAS, RAB1B), methyltransferases (SET D8), receptors associated factors (T RAF2, GRB2), growth factors (FGF20), autophagy (BECN1, AT G14), apoptotic regulators (BCL2), transcription factors (T Fs) (CREB1, RUNX1, RUNX2) and gene regulators (CCND1, HIF1A); and others, including some novel gene candidates (CREB1, FGF20, IFI27), that have never been implicated in EC earlier. The expression of hsa-miR-433-3p showed significant predictive relevance (Fold Change = 1.8, AUC = 0.736, Mann-Whitney test p-value = 6.1 e- 14) suggesting its predictive relevance in assessing patients' response to chemotherapy. The hsamiR- 188-3p targets autophagic and apoptotic regulators and its upregulation in endometriosis may be used as for the early stage diagnostic purpose. The hsa-miR-502-5p targets SET D8, T RAF2 and others and suggests additional genomic/epigenomic molecular targets for promising therapeutic interventions in EC. Predicted miRNAs target a number of mRNAs having varied functional impacts and offer an in-depth mechanistic insights for expatiating the biological and regulatory role in EC.Communicated by Ramaswamy H. Sarma.