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1.
Crit Rev Food Sci Nutr ; : 1-45, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838143

RESUMO

Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental factors lead to BC development and on this basis, several preventive - screening and therapeutic interventions have been developed. Hormones, both in the form of endogenous hormonal signaling or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top of these, breast microbiota includes both species with an immunomodulatory activity enhancing the host's response against cancer cells and species producing proinflammatory cytokines associated with BC development. Identification of novel multitargeted therapeutic agents with poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing body of research has emphasized the potential of natural compounds derived from medicinal plants and microbial species as complementary BC treatment regimens, including dietary supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile, Origanum dayi Post, Urtica membranacea Poir. ex Savigny, Krameria lappacea (Dombey) Burdet & B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05 have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in tumors' chemosensitivity, antioxidant activity and modulation of BC - associated molecular pathways. Further, bioactive compounds like 3,3'-diindolylmethane, epigallocatechin gallate, genistein, rutin, resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest for the researchers and clinicians because these natural agents have multimodal action and act via multiple ways in managing the BC and most of these agents are regularly available in our food and fruit diets. Evidence from clinical trials suggests that such products had major potential in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects. We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings of medicinal plants and microbial metabolites in BC management. The future perspectives on the translation of these findings to the personalized treatment of BC are provided and discussed.

2.
Rural Remote Health ; 20(1): 5457, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31931588

RESUMO

INTRODUCTION: To address regional differences in the distribution of health workers between rural and urban areas, the Nepal government has adopted the policy of deploying fresh medical graduates to remote areas for 2 years under a compulsory bonding service program. However, the impact of such an approach of redistribution of human resources for health is not well understood, nor is the experience of the health workers who are deployed. This study aimed to understand the experience of the medical graduates who have served under the bonding service program and suggest ways to improve the program as well as to make health service provision easier through the young doctors. METHODS: A semi-structured questionnaire-based survey was administered online to 69 young medical doctors who had worked under the bonding service program. The responses were analysed qualitatively and the findings were presented in separate pre-established domains. RESULTS: Most young doctors felt they were not adequately prepared for the bonding service program. Adapting to the deployed place and to the local culture was a challenge to some young doctors, which hindered their potential to serve the local community. Most found the response from the rural communities to be positive even though they faced some challenges in the beginning. While the young doctors found serving the rural communities motivating, they felt that they were limited in their capacity to provide an optimal level of health service due to limitations of infrastructure and medical equipment. They also felt that the compulsory bonding program had stunted their growth potential as medical doctors without adequately compensating them for their time and service. CONCLUSION: Despite the program's noble intentions, the medical doctors who were involved with the bonding service program felt that the program had yet to address several basic needs of the doctors who were deployed for service provision. In order to motivate the doctors to work in rural areas in future after the compulsory binding has ended, the stakeholders need to address the existing gaps in policies and infrastructure.


Assuntos
Programas Governamentais/organização & administração , Mão de Obra em Saúde/organização & administração , Programas Obrigatórios/organização & administração , Médicos/psicologia , Serviços de Saúde Rural/provisão & distribuição , Adulto , Feminino , Humanos , Masculino , Nepal , Pesquisa Qualitativa , População Rural , Inquéritos e Questionários
3.
J Biosoc Sci ; 48(2): 249-66, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26008148

RESUMO

This paper assesses the factors influencing mistimed and unwanted pregnancies in Nepal separately using data from the 2011 Nepal Demographic and Health Survey. Women who had given birth within the five years before the survey were interviewed about the intendedness of their last pregnancy. The data were analysed with a chi-squared test, followed by multiple logistic regression analysis. Among the total 5391 participants, 11.29% and 13.13% reported their last pregnancy as mistimed and unwanted respectively. Logistic regression analysis showed that women from the hill region were more likely to report mistimed pregnancy, while women from the Western and Far-Western development regions were less likely to report mistimed pregnancy. Education status was positively correlated with the reporting of mistimed pregnancy. Women involved in agriculture, with full autonomy on household decision, with some exposure to mass media, belonging to higher age group and having third or higher parity were less likely to report mistimed pregnancy. Similarly, women from the Western development region had relatively higher odds of reporting unwanted pregnancy. Women with husbands involved in a paid job had lower odds of unwanted pregnancy. Women's autonomy was also positively correlated with unwanted pregnancy. Women with the intention to use contraceptive had lower odds of unwanted pregnancy. Interventions targeting the factors identified by this study could be useful in reduction of mistimed and unwanted pregnancies among Nepali women.


Assuntos
Gravidez não Planejada/etnologia , Gravidez não Desejada/etnologia , Adolescente , Adulto , Demografia/estatística & dados numéricos , Características da Família/etnologia , Serviços de Planejamento Familiar/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Nepal , Razão de Chances , Paridade , Gravidez , Fatores Socioeconômicos , Adulto Jovem
4.
Pathol Res Pract ; 254: 155131, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309018

RESUMO

Diabetes has been a significant healthcare problem worldwide for a considerable period. The primary objective of diabetic treatment plans is to control the symptoms associated with the pathology. To effectively combat diabetes, it is crucial to comprehend the disease's etiology, essential factors, and the relevant processes involving ß-cells. The development of the pancreas, maturation, and maintenance of ß-cells, and their role in regular insulin function are all regulated by PDX1. Therefore, understanding the regulation of PDX1 and its interactions with signaling pathways involved in ß-cell differentiation and proliferation are crucial elements of alternative diabetes treatment strategies. The present review aims to explore the protective role of PDX1 in ß-cell proliferation through signaling pathways. The main keywords chosen for this review include "PDX1 for ß-cell mass," "ß-cell proliferation," "ß-cell restoration via PDX1," and "mechanism of PDX1 in ß-cells." A comprehensive literature search was conducted using various internet search engines, such as PubMed, Science Direct, and other publication databases. We summarize several approaches to generating ß-cells from alternative cell sources, employing PDX1 under various modified growth conditions and different transcriptional factors. Our analysis highlights the unique potential of PDX1 as a promising target in molecular and cell-based therapies for diabetes.


Assuntos
Diabetes Mellitus , Proteínas de Homeodomínio , Células Secretoras de Insulina , Transativadores , Humanos , Diabetes Mellitus/terapia , Diabetes Mellitus/metabolismo , Proteínas de Homeodomínio/metabolismo , Células Secretoras de Insulina/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo
5.
Curr Protein Pept Sci ; 25(1): 4-11, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37183462

RESUMO

The human genetic structure undergoes continuous wear and tear process due to the mere presence of extrinsic as well as intrinsic factors. In normal physiological cells, DNA damage initiates various checkpoints that may activate the repair system or induce apoptosis that helps maintain cellular integrity. While in cancerous cells, due to alterations in signaling pathways and defective checkpoints, there exists a marked deviation of error-free DNA repairing/synthesis. Currently, cancer therapy targeting the DNA damage response shows significant therapeutic potential by tailoring the therapy from non-specific to tumor-specific activity. Recently, numerous drugs that target the DNA replicating enzymes have been approved or some are under clinical trial. Drugs like PARP and PARG inhibitors showed sweeping effects against cancer cells. This review highlights the mechanistic study of different drug categories that target DNA replication and thus depicts the futuristic approach of targeted therapy.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Dano ao DNA , Reparo do DNA , Replicação do DNA , DNA
6.
Curr Med Chem ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38445701

RESUMO

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

7.
Front Public Health ; 12: 1385125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689763

RESUMO

The stillbirth rate among Aboriginal and Torres Strait Islander women and communities in Australia is around double that of non-Indigenous women. While the development of effective prevention strategies during pregnancy and improving care following stillbirth for women and families in communities has become a national priority, there has been limited progress in stillbirth disparities. With community permission, this study aimed to gain a better understanding of community experiences, perceptions, and priorities around stillbirth. We undertook an Indigenous researcher-led, qualitative study, with community consultations guided by a cultural protection protocol and within an unstructured research framework. A total of 18 communities were consulted face-to-face through yarning interviews, focus groups and workshops. This included 54 community member and 159 health professional participants across remote, regional, and urban areas of Queensland, Western Australia, Victoria, South Australia, and Northern Territory. Thematic analysis of consultation data identified common themes across five focus/priority areas to address stillbirth: Stillbirth or Sorry Business Baby care needs to be family-centered; using Indigenous "ways of knowing, being, and doing" to ensure cultural safety; application of Birthing on Country principles to maternal and perinatal care; and yarning approaches to improve communication and learning or education. The results underscore the critical need to co-design evidence-based, culturally appropriate, and community-acceptable resources to help reduce existing disparities in stillbirth rates.


Assuntos
Grupos Focais , Pesquisa Qualitativa , Natimorto , Adulto , Feminino , Humanos , Masculino , Gravidez , Austrália , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Entrevistas como Assunto , Natimorto/psicologia
8.
Nutr Metab (Lond) ; 21(1): 26, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755627

RESUMO

Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

9.
Curr Pharm Biotechnol ; 24(1): 164-187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35410596

RESUMO

Skin is the largest non-parenchymal organ of the human body. It constitutes a natural barrier against pathogens and harmful environmental exposures and contributes to the human body's homeostasis. Conditions affecting the skin range from infections and injury to autoimmune diseases and cancer. Herbs have been used to treat dermatological conditions for a long time. Traditional approaches to delivering herbs to the skin include ointments, gels, creams, and lotions. However, poor lipophilicity or hydrophilicity in most herbal preparations results in limited bioavailability and poor penetration, restricting their effectiveness. Nanotechnology-based approaches have major potential, showing more promising results in enhancing transdermal penetration than traditional approaches. This review article summarizes such advances and sheds light on future directions in using nanotechnology-based strategies.


Assuntos
Absorção Cutânea , Pele , Humanos , Pele/metabolismo , Administração Cutânea , Higiene da Pele/métodos , Nanotecnologia
10.
Curr Neuropharmacol ; 21(4): 777-786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825704

RESUMO

Phytochemicals or natural products have been studied extensively for their potential in the treatment of neurodegenerative diseases (NDs) like Parkinson's disease, Alzheimer's disease, etc. The neuronal structure loss and progressive dysfunction are the main characteristics of these diseases. In spite of impressive and thorough knowledge of neurodegenerative molecular pathways, little advancement has been found in the treatment of the same. Moreover, it was proved that natural products can be used efficiently in the treatment of NDs while certain issues regarding the patient's safety and clinical data are still existing. As ND is a bunch of diseases and it will start the myriad of pathological processes, active targeting of the molecular pathway behind ND will be the most efficient strategy to treat all ND-related diseases. The targeting pathway must prevent cell death and should restore the damaged neurons. In the treatment of ND and related diseases, natural products are playing the role of neuroprotective agents. This review will target the therapeutic potential of various phytochemicals which shows neuroprotective action.


Assuntos
Doença de Alzheimer , Produtos Biológicos , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico
11.
Curr Pharm Biotechnol ; 24(11): 1420-1429, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36578251

RESUMO

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.


Assuntos
Diabetes Mellitus , Nanopartículas , Humanos , Sistemas de Liberação de Medicamentos , Lipossomos , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Polímeros/uso terapêutico , Portadores de Fármacos
12.
Pathophysiology ; 30(1): 37-47, 2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36810424

RESUMO

This study aims to investigate the effect of resveratrol on systemic inflammatory response and metabolic disorder in rats fed a high-fructose high-lipid diet (HFHLD) and exposed to round-the-clock lighting (RCL). 21 adult male Wistar rats were randomly divided into 3 groups: control (group 1, n = 7); HFHLD for 8 weeks + round-the-clock lighting (RCL) (group 2, n = 7); HFHLD + RCL + Resveratrol (in a daily dose of 5 mg/kg intragastrically (group 3, n = 7). Results show that the combined effect of HFHLD and RCL reduces the serum melatonin (p < 0.001) and accelerates pro-inflammatory activities, oxidative stress, and metabolic disorder. There is a significant increase in the serum tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) (both p < 0.001), blood malondialdehyde-thiobarbituric acid adducts (MDA-TBA2) (p < 0.001), serum glucose (p < 0.01), insulin concentration, and the homeostatic model assessment insulin resistance (HOMA-IR) index (both p < 0.001), serum with very low-density lipoprotein (VLDL), and triacylglycerol (TAG) (both p < 0.001). At the same time, the decrease in the serum high-density lipoprotein (HDL) level (p < 0.001) is observed in the HFHLD + RCL group compared to the control. In the HFHLD + RCL + Resveratrol group, hypomelatonaemia (p < 0.001), pro-inflammatory actions, oxidative stress, and metabolic disorder were mitigated. Resveratrol can cause a significant rise in the serum melatonin and reduce serum TNF-α and CRP levels (both p < 0.001), blood MDA-TBA2 (p < 0.001), serum glucose (both p < 0.01), insulin concentration, and HOMA-IR (both p < 0.001), serum VLDL and TAG (both p < 0.001) compared to the group 2, while serum HDL level increases (p < 0.01). Resveratrol attenuates pro-inflammatory responses and prevents considerable metabolic disorder in rats fed HFHLD under RCL.

13.
Curr Pharm Biotechnol ; 24(14): 1727-1739, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36861800

RESUMO

COVID-19, an extremely transmissible and pathogenic viral disease, triggered a global pandemic that claimed lives worldwide. To date, there is no clear and fully effective treatment for COVID-19 disease. Nevertheless, the urgency to discover treatments that can turn the tide has led to the development of a variety of preclinical drugs that are potential candidates for probative results. Although most of these supplementary drugs are constantly being tested in clinical trials against COVID-19, recognized organizations have aimed to outline the prospects in which their use could be considered. A narrative assessment of current articles on COVID-19 disease and its therapeutic regulation was performed. This review outlines the use of various potential treatments against SARS-CoV-2, categorized as fusion inhibitors, protease inhibitors, and RNA-dependent RNA polymerase inhibitors, which include antiviral drugs such as Umifenovir, Baricitinib, Camostatmesylate, Nafamostatmesylate, Kaletra, Paxlovide, Darunavir, Atazanavir, Remdesivir, Molnupiravir, Favipiravir, and Ribavirin. To understand the virology of SARS-CoV-2, potential therapeutic approaches for the treatment of COVID-19 disease, synthetic methods of potent drug candidates, and their mechanisms of action have been addressed in this review. It intends to help readers approach the accessible statistics on the helpful treatment strategies for COVID-19 disease and to serve as a valuable resource for future research in this area.


Assuntos
Antivirais , COVID-19 , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , SARS-CoV-2 , Darunavir/farmacologia , Inibidores de Proteases/farmacologia
14.
Curr Med Chem ; 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37828674

RESUMO

Nanomedicine's application of nanotechnology in medicine holds tremendous potential for diagnosing and treating life-threatening diseases such as cancer. Unlike conventional therapies, nanomedicine offers a promising strategy to enhance clinical outcomes while minimizing severe side effects. The principle of drug targeting enables specific delivery of therapeutic agents to their intended sites, making it a more precise and effective therapy. Combination strategies, such as the co-delivery of chemotherapeutic drugs with nucleic acids or receptor-specific molecules, are being employed to enhance therapeutic outcomes. Nanocarriers and drug delivery systems designed using these approaches offer resourceful co-delivery of therapeutic agents for anticancer therapy. Targeted drug delivery via nanotechnology-based techniques has become an urgent need and has shown significant improvements in therapeutic implications, pharmacokinetics, specificity, reduced toxicity, and biocompatibility. This review discusses the extrapolation of nanomaterials for developing innovative and novel drug delivery systems for effective anticancer therapy. Additionally, we explore the role of nanotechnology-based concepts in drug delivery research.

15.
Narra J ; 3(2): e147, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38454981

RESUMO

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

16.
Narra J ; 3(3): e152, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38455614

RESUMO

Rubus ellipticus is a native plant to India's tropical and subtropical regions and has been used as a traditional medicinal. The aim of study was to identify and evaluate the antimicrobial and anti-arthritis activities of hydroethanolic extract of R. ellipticus leaves (HEERE). The leaves were collected from the Narkanda Valley, India and were shade-dried and finely ground to produce the powder. The hydroethanolic extract was utilized for phytochemical analysis to determine the existence of carbohydrate, phenolic, terpenoid, flavonoid, saponin, glycoside, tannin, protein, and alkaloid. The HEERE was futher analyzed by gas chromatography-mass spectrometry (GC-MS) for the characterization of the phytoconstituents. The antimicrobial activity was tested against Escherichia coli, Staphylococcus aureus as well as Aspergillus niger. To assess its anti-arthritic activities, different doses of HEERE were given orally to complete Freund's adjuvant (CFA)-induced albino Wistar rats for twenty-one days. The GC-MS analysis of hydroethanolic extracts from leaves detected and identified the presence of 33 phytochemical compounds. HEERE showed significant effects against E. coli, S. aureus, and A. niger strains at 600 ppm. Our data indicated that HEERE 200 mg/kg was more effective than 50 mg/kg as anti-arthritis. Paw volume, ankle-joint diameter, the number leucocytes, and erythrocyte sedimentation rate (ESR) were all significantly reduced in experimental rats. Furthermore, when compared to respective standard drugs, the body weight, erythrocyte, hemoglobin, and synobium healing effect have all improved. These data demonstrated the potential of R. ellipticus for the long-term investigation of antimicrobial and anti-arthritic properties.

17.
Chem Biol Interact ; 382: 110631, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37451664

RESUMO

Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.


Assuntos
Neoplasias , Telomerase , Humanos , Telomerase/genética , Telomerase/metabolismo , Envelhecimento , Neoplasias/tratamento farmacológico , Neoplasias/genética , Telômero/metabolismo , Células-Tronco/metabolismo , Senescência Celular
18.
Curr Med Chem ; 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37497712

RESUMO

Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aß (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.

19.
Curr Pharm Biotechnol ; 23(13): 1581-1595, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34967294

RESUMO

BACKGROUND: The development of advanced treatment of triple-negative breast cancer (TNBC) is the utmost need of an era. TNBC is recognized as the most aggressive, metastatic cancer and the leading cause of mortality in females worldwide. The lack of expression of triple receptors namely, estrogen, progesterone, and human epidermal receptor 2 defined TNBC. OBJECTIVE: The current review introduced the novel biomarkers such as miRNA and family, PD1, EGFR, VEGF, TILs, P53, AR and PI3K, etc. contributed significantly to the prognosis and diagnosis of TNBC. Once diagnosed, the advanced utilization approaches are available for TNBC because of the limitations of chemotherapy. Novel approaches include lipid-based (liposomes, SLN, NLC, and SNEDDS), polymer-based (micelle, nanoparticles, dendrimers, and quantum dots), advanced nanocarriers such as (exosomes, antibody and peptide-drug conjugates), and carbonbased nanocarriers (Carbon nanotubes, and graphene oxide). Lipid-based delivery is used for excellent carriers for hydrophobic drugs, biocompatibility, and lesser systemic toxicities than chemotherapeutic agents. Polymer-based approaches are preferred over lipids for providing longer circulation time, nanosize, high loading efficiency, high linking, avoiding the expulsion of drugs, targeted action, diagnostic and biosensing abilities. Advanced approaches like exosomes, conjugated moieties are preferred over polymeric for possessing potency, high penetrability, biomarkers, and avoiding the toxicity of tissues. Carbon-based gained wide applicability for their unique properties like a versatile carrier, prognostic, diagnostic, sensing, photodynamic, and photothermal characteristics. CONCLUSION: The survival rate can be increased by utilizing several kinds of biomarkers. The advanced approaches can also be significantly useful in the prognosis and theranostic of triplenegative breast cancer. One of the biggest successes in treating with nanotechnology-based approaches is the marked reduction of systemic toxicity with high therapeutic effectiveness compared with chemotherapy, surgery, etc. The requirements such as prompt diagnosis, longer circulation time, high efficiency, and high potency can be fulfilled with these nanocarriers.


Assuntos
Dendrímeros , MicroRNAs , Nanotubos de Carbono , Neoplasias de Mama Triplo Negativas , Receptores ErbB/metabolismo , Receptores ErbB/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Humanos , Lipídeos , Lipossomos , Micelas , MicroRNAs/uso terapêutico , Nanotecnologia , Fosfatidilinositol 3-Quinases/metabolismo , Polímeros , Progesterona/uso terapêutico , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteína Supressora de Tumor p53/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Curr Pharm Des ; 28(33): 2690-2703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35676841

RESUMO

Due to the heap of data sets available for drug discovery, modern drug discovery has taken the shape of big data. Usage of Artificial intelligence (AI) can help to modify drug discovery based on big data to precised, knowledgeable data. The pharmaceutical companies have already geared their departments for this and started a race to search for new novel drugs. The AI helps to predict the molecular structure of the compound and its in-vivo vs. in-vitro characteristics without hampering life, thus saving time and economic loss. Clinical studies, electronic records, and images act as a helping hand for the development. The data mining and curation techniques help explore the data with a single click. AI in big data analysis has paved the red carpet for future rational drug development and optimization. This review's objective is to familiarise readers with various advances in the AI field concerning software, firms, and other tools working in easing out the labor of the drug discovery journey.


Assuntos
Inteligência Artificial , Descoberta de Drogas , Humanos , Descoberta de Drogas/métodos , Big Data , Mineração de Dados , Desenvolvimento de Medicamentos
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