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1.
Fish Physiol Biochem ; 44(1): 95-108, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28822029

RESUMEN

In the present study, full-length CYP1A cDNA from Catla catla (Catla) has been identified, and its real-time quantitative reverse transcription PCR (qRT-PCR) expression has been evaluated in different tissues, developmental stages (0, 3, 6, 12 and 24 h and 5, 7 and 9 days post-fertilization) and copper sulphate and benzo(a)pyrene (BaP)-treated 5-day post-fertilization (dpf) larvae (6 to 6.5 mm). Various structural, comparative and phylogenetic analyses of the deduced amino acid sequence revealed that the identified gene of Catla belongs to the CYP1A1 subfamily. Among different tissues of Catla, the highest CYP1A expression was observed in the kidney followed by the liver, muscle, gill, intestine and brain. CYP1A mRNA expression was detected during all the larval developmental stages, including the unfertilized egg with the highest expression on 9 dpf. BaP (3.5 ppb) and copper sulphate (sublethal dose 0.516 ppm) challenge test for 96 h to Catla larvae revealed the highest CYP1A1 expression at 48 h post-challenge. CYP1A1 transcript also showed a concentration-dependent increase in expression following exposure at 1.75 and 3.5 ppb of BaP for 48 h. Its expression profiling indicates that it is functional at early developmental stages. It can also be used to develop a specific biomarker tool for monitoring environmental pollution.


Asunto(s)
Benzo(a)pireno/farmacología , Sulfato de Cobre/farmacología , Cipriniformes/genética , Citocromo P-450 CYP1A1/genética , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Cipriniformes/crecimiento & desarrollo , Citocromo P-450 CYP1A1/metabolismo , ADN Complementario/genética , ADN Complementario/metabolismo , Larva/genética , Larva/metabolismo , Modelos Moleculares , Filogenia , Conformación Proteica
2.
Fish Shellfish Immunol ; 47(2): 868-77, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26475365

RESUMEN

The present study was conducted to investigate the strategy to mitigate the immunosuppressive and oxidative stress effect of gelatinized starch in fingerling of Labeo rohita. Fingerlings were either maintained at ambient water temperature (26 °C) or exposed to 32 °C for one week and then subjected to 26 °C for four weeks. Both groups were fed with isoproteinous (30% crude protein) diets containing gelatinized (G) or non-gelatinized (NG) starch. After 5 weeks of feeding trial, fingerlings were challenged by Aeromonas hydrophila and survival rate was recorded for the next 7 days. Serum cortisol and glucose content was significantly (p < 0.05) higher in G starch fed group and decreased with the increase in temperature from 26 to 32 °C, which was consistent for next four week after decrease in temperature from 32 to 26 °C. Lower respiratory burst activity and serum total protein and globulin content in G starch fed group at 26 °C significantly (p < 0.05) increased after elevation of temperature from 26 to 32 °C and levelled off to NG starch fed group. Liver superoxide dismutase (SOD) and catalase (CAT) activity of G starch fed group was significantly higher in group reared at 32 °C compared to 26 °C. After challenge, fish fed G starch showed lower survival rate than that of fish fed NG starch. Subsequently, exposure of elevated temperature (32 °C) for one week significantly increased the survival rate of G starch fed group and levelled off to NG starch fed group. The results of this study indicated that dietary G starch may cause metabolic stress of fingerling L. rohita, as might consequently lead to the decrease antioxidant abilities, depressed immunity and reduced resistance to A. hydrophila infection. Subsequently, exposure of elevated temperature (32 °C) for one week mitigate immunosuppressive and oxidative stress effect of dietary G starch.


Asunto(s)
Cyprinidae , Carbohidratos de la Dieta/metabolismo , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Tolerancia Inmunológica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Aeromonas hydrophila/fisiología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Enfermedades de los Peces/microbiología , Gelatina/química , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/microbiología , Almidón/metabolismo , Temperatura
3.
Curr Rheumatol Rev ; 20(1): 27-38, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37694798

RESUMEN

Osteoarthritis is a degenerative joint disease that causes the cartilage and bone underneath the joint to break down. This causes pain and stiffness. Resveratrol, a polyphenolic compound found in various vegetables, fruits, and red wine, has been studied for its beneficial effects on osteoarthritis. Resveratrol has been shown to target a variety of pathways, including the NF-κB, PI3K/Akt, MAPK/ERK, and AMPK pathways. In particular, resveratrol has been studied for its potential use in treating osteoarthritis, and it has been shown to reduce inflammation, reduce cartilage degradation, and improve joint function. In this review, we discuss the evidence for the pharmacological use of resveratrol in minimizing soft tissue damage associated with osteoarthritis. We summarize the studies on how resveratrol has anti-inflammatory, anti-oxidant, and anti-apoptotic effects, as well as effects on cartilage degradation, osteoblast and synoviocyte proliferation, and cytokine production. We also discuss the possible mechanisms of action of resveratrol in osteoarthritis and its potential as a therapeutic agent. Finally, we discuss the potential risks and adverse effects of long-term resveratrol supplementation. Overall, resveratrol has been found to be a possible treatment for osteoarthritis because of its anti-inflammatory, anti-oxidant, and anti-apoptotic properties, and its ability to control the production of enzymes that break down cartilage, osteoblasts, and synoviocytes. Although numerous clinical studies have demonstrated resveratrol's efficacy as an osteoarthritis management agent, further long-term studies are needed to better understand the safety and potential benefits of using resveratrol for osteoarthritis management.


Asunto(s)
Antioxidantes , Osteoartritis , Humanos , Resveratrol/uso terapéutico , Antioxidantes/farmacología , Fosfatidilinositol 3-Quinasas/uso terapéutico , Antiinflamatorios/uso terapéutico , Osteoartritis/tratamiento farmacológico
4.
Curr Gene Ther ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38738727

RESUMEN

: Neurodegenerative disorders pose significant challenges in the realm of healthcare, as these conditions manifest in complex, multifaceted ways, often attributed to genetic anomalies. With the emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, a new frontier has been unveiled in the quest for targeted, precise genetic manipulation. This abstract explores the recent advancements and potential applications of CRISPR-based therapies in addressing genetic components contributing to various neurodegenerative disorders. The review delves into the foundational principles of CRISPR technology, highlighting its unparalleled ability to edit genetic sequences with unprecedented precision. In addition, it talks about the latest progress in using CRISPR to target specific genetic mutations linked to neurodegenerative diseases like Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. It talks about the most important studies and trials that show how well and safely CRISPR-based therapies work. This shows how this technology can change genetic variants that cause diseases. Notably, the discussion emphasizes the challenges and ethical considerations associated with the implementation of CRISPR in clinical settings, including off-target effects, delivery methods, and long-term implications. Furthermore, the article explores the prospects and potential hurdles in the widespread application of CRISPR technology for treating neurodegenerative disorders. It touches upon the need for continued research, improved delivery mechanisms, and ethical frameworks to ensure responsible and equitable access to these groundbreaking therapies.

5.
Curr Protein Pept Sci ; 25(7): 507-526, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38561605

RESUMEN

Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.


Asunto(s)
Enfermedades Neurodegenerativas , Péptidos , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Péptidos/uso terapéutico , Péptidos/química , Péptidos/farmacología , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Inhibidores de la Colinesterasa/uso terapéutico , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química
6.
Artículo en Inglés | MEDLINE | ID: mdl-38486388

RESUMEN

Joints and arthritic conditions are among the most dangerous illnesses that humans have ever encountered and it is even more worrying that there is no recognized treatment for arthritis. The researchers looked for safer alternatives, such as herbal medicines, because the traditional treatments used to treat severe joint inflammatory issues have several negative side effects. A ligand-coated nanomedicine can bind to receptors that are overexpressed by cells in chronically inflammatory tissues, increasing its efficacy and reducing its systemic side effects. This is because the pathophysiology of rheumatoid arthritis suggests that macrophages and overexpressed molecules exist within inflamed tissues, which increases permeability and allows nanomedicines to accumulate in inflamed tissue and cause retention phenomena. The anti-arthritic properties of a variety of plants, their components, extracts, and phyto-isolates have been studied to date. These plant compounds can pose stability and delivery problems, which restricts their efficacy as a treatment for inflammatory diseases. The multifunctional and adaptable features of different nanoparticles can help herbal remedies based on nanotechnology get beyond the delivery constraints of different natural ingredients. The application of nanoformulations in tissue engineering is an additional strategy for delivering drugs directly to bone and cartilage in RA patients. The medication is more therapeutically effective due to nanoformulation's improved synovium and cartilage absorption, accumulation, and penetration at inflammatory joints. Herbal medications with a nanotechnology foundation exhibit superior pharmacokinetic and drug delivery qualities, aid in better oral absorption, regulate drug release, boost in vivo retention capacity, target delivery, and have synergistic effects. This review provides an update on the use of herbal medicines based on nanotechnology, which show promise in treating arthritis and other ailments.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39005132

RESUMEN

Alzheimer's Disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive function, including memory loss, reasoning difficulties, and disorientation. Its hallmark features include the formation of neurofibrillary tangles and neuritic plaques in the brain, disrupting normal neuronal function. Neurofibrillary tangles, composed of phosphorylated tau protein and neuritic plaques, containing amyloid-ß protein (Aß) aggregates, contribute to the degenerative process. The discovery of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in 1999 revolutionized our understanding of AD pathogenesis. BACE1 plays a crucial role in the production of Aß, the toxic protein implicated in AD progression. Elevated levels of BACE1 have been observed in AD brains and bodily fluids, underscoring its significance in disease onset and progression. Despite setbacks in clinical trials of BACE1 inhibitors due to efficacy and safety concerns, targeting BACE1 remains a promising therapeutic strategy for early-stage AD. Natural flavonoids have emerged as potential BACE1 inhibitors, demonstrating the ability to reduce Aß production in neuronal cells and inhibit BACE1 activity. In our review, we delve into the pathophysiology of AD, highlighting the central role of BACE1 in Aß production and disease progression. We explore the therapeutic potential of BACE1 inhibitors, including natural flavonoids, in controlling AD symptoms. Additionally, we provide insights into ongoing clinical trials and available patents in this field, shedding light on future directions for AD treatment research.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38766821

RESUMEN

Neurological disorders present a formidable challenge in healthcare, necessitating the continuous exploration of innovative therapeutic avenues. This review delves into the burgeoning field of natural diterpenoid derivatives and their promising role in addressing neurological disorders. Derived from natural sources, these compounds exhibit a diverse range of pharmacological properties, positioning them as potential agents for treating conditions such as Alzheimer's and Parkinson's disease. The review highlights recent advancements, shedding light on the multifaceted mechanisms through which diterpenoid derivatives exert their effects, from antiinflammatory to neuroprotective actions. As the scientific community navigates the translational journey from bench to bedside, integrating these natural compounds into neurotherapeutics emerges as a compelling prospect. This exploration of the therapeutic frontiers of natural diterpenoid derivatives signifies a significant step towards innovative and effective strategies in the management of neurological disorders. It highlights the potential of natural compounds to revolutionize neurotherapeutics.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38716551

RESUMEN

Cancer remains a significant global health challenge, necessitating innovative approaches to enhance the efficacy and specificity of therapeutic interventions while minimizing adverse effects on healthy tissues. Nanotechnology has emerged as a promising avenue in cancer treatment, offering novel strategies for targeted drug delivery. Nanoparticles, liposomes, and polymer-based systems have played pivotal roles in revolutionizing cancer therapy. Nanotechnology possesses unique physicochemical properties, enabling efficient encapsulation of therapeutic agents and controlled and prolonged release at tumour sites. Advancement in formulations using nanotechnology has made it possible to make multifunctional systems that respond to the microenvironment of a tumour by releasing payloads in response to changes in pH, temperature, or enzymes. Stimuli-responsive polymers can release drugs in response to external cues, enabling site-specific drug release and minimizing systemic exposure. This review explores recent studies and preclinical trials that show how nanoparticles, liposomes, and polymerbased systems could be used to treat cancer, discussing challenges such as scalability, regulatory approval, and potential toxicity concerns along with patents published recently.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38441025

RESUMEN

Hyperlipidemia, characterized by elevated levels of lipids in the blood, represents a major risk factor for cardiovascular diseases, a leading cause of morbidity and mortality worldwide. Conventional pharmacological interventions have been effective in managing hyperlipidemia, but concerns about side effects and long-term use have prompted interest in alternative approaches, particularly the use of nutraceuticals. This comprehensive review aims to summarize and critically evaluate the current body of knowledge surrounding the role of nutraceuticals in the management of hyperlipidemia. We provide an overview of the different classes of nutraceuticals, including plant sterols, omega-3 fatty acids, soluble fiber, antioxidants, and various herbal extracts, which have been investigated for their lipid-lowering properties. The mechanisms of action of these nutraceuticals are discussed, highlighting their ability to modulate lipid metabolism, reduce oxidative stress, and promote cardiovascular health. Furthermore, we review the results of clinical trials and epidemiological studies that have assessed the efficacy of nutraceutical interventions in lowering cholesterol levels, improving lipid profiles, and reducing the risk of cardiovascular events. In addition to their lipid-lowering effects, we examine the safety profile, dosage recommendations, and potential interactions of nutraceuticals with conventional lipid-lowering medications. We also address the importance of patient adherence to dietary and lifestyle modifications in conjunction with nutraceutical supplementation. While nutraceuticals offer a promising avenue for managing hyperlipidemia, we emphasize the need for further research to establish evidence-based guidelines for their use in clinical practice. Challenges related to standardization, quality control, and regulatory considerations are also discussed. In conclusion, this comprehensive review provides valuable insights into the potential of nutraceuticals as adjunctive or alternative therapies for managing hyperlipidemia. While further research is needed, the accumulating evidence suggests that nutraceuticals can play a valuable role in promoting cardiovascular health and reducing the burden of hyperlipidemia- related diseases.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38288793

RESUMEN

Pharmaceutical design has made significant advancements in recent years, leading to the development of novel therapeutics with unprecedented efficacy and safety profiles. This review highlights the potential of these innovations to revolutionize healthcare and improve patient outcomes. The application of cutting-edge technologies like artificial intelligence, machine learning, and data mining in drug discovery and design has made it easier to find potential drug candidates. Combining big data and omics has led to the discovery of new therapeutic targets and personalized medicine strategies. Nanoparticles, liposomes, and microneedles are examples of advanced drug delivery systems that allow precise control over drug release, better bioavailability, and targeted delivery to specific tissues or cells. This improves the effectiveness of the treatment while reducing side effects. Stimuli-responsive materials and smart drug delivery systems enable drugs to be released on demand when specific internal or external signals are sent. Biologics and gene therapies are promising approaches in pharmaceutical design, offering high specificity and potency for treating various diseases like cancer, autoimmune disorders, and infectious diseases. Gene therapies hold tremendous potential for correcting genetic abnormalities, with recent breakthroughs demonstrating successful outcomes in inherited disorders and certain types of cancer. Advancements in nanotechnology and nanomedicine have paved the way for innovative diagnostic tools and therapeutics, such as nanoparticle-based imaging agents, targeted drug delivery systems, gene editing technologies, and regenerative medicine strategies. Finally, the review emphasizes the importance of regulatory considerations, ethical challenges, and future directions in pharmaceutical design. Regulatory agencies are adapting to the rapid advancements in the field, ensuring the safety and efficacy of novel therapeutics while fostering innovation. Ethical considerations regarding the use of emerging technologies, patient privacy, and access to advanced therapies also require careful attention.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38778607

RESUMEN

OBJECTIVE: The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus. MATERIALS AND METHODS: Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue. RESULTS: The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions. CONCLUSION: These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

13.
Curr Top Med Chem ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39108007

RESUMEN

Neurological disorders, characterized by oxidative stress (OS) and inflammation, have become a major global health concern. Redox reactions play a vital role in regulating the balance of the neuronal microenvironment. Specifically, the imbalance leads to a significant weakening of the organism's natural defensive mechanisms. This, in turn, causes the development of harmful oxidative stress, which plays a crucial role in the onset and progression of neurodegenerative dis-eases. The quest for effective therapeutic agents has led to significant advancements in the syn-thesis of antioxidant derivatives. This review provides a comprehensive overview of the recent developments in the use of novel antioxidant compounds with potential pharmacological applica-tions in the management of neurological disorders. The discussed compounds encompass a di-verse range of chemical structures, including polyphenols, vitamins, flavonoids, and hybrid mole-cules, highlighting their varied mechanisms of action. This review also focuses on the mechanism of oxidative stress in developing neurodegenerative disease. The neuroprotective effects of these antioxidant derivatives are explored in the context of specific neurological disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The ultimate goal is to pro-vide effective treatments for these debilitating conditions and improve the quality of life for pa-tients.

14.
Artículo en Inglés | MEDLINE | ID: mdl-39129294

RESUMEN

A family of peptides known as bioactive peptides has unique physiological properties and may be used to improve human health and prevent illness. Because bioactive peptides impact the immunological, endocrine, neurological, and cardiovascular systems, they have drawn a lot of interest from researchers. According to recent studies, bioactive peptides have a lot to offer in the treatment of inflammation, neuronal regeneration, localized ischemia, and the blood-brain barrier. It investigates various peptide moieties, including antioxidative properties, immune response modulation, and increased blood-brain barrier permeability. It also looks at how well they work as therapeutic candidates and finds promising peptide-based strategies for better outcomes. Furthermore, it underscores the need for further studies to support their clinical utility and suggests that results from such investigations will enhance our understanding of the pathophysiology of these conditions. In order to understand recent advances in BPs and to plan future research, academic researchers and industrial partners will find this review article to be a helpful resource.

15.
Eur J Pharmacol ; 980: 176873, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39117264

RESUMEN

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by cognitive, motor, and psychiatric symptoms. Despite significant advances in understanding the underlying molecular mechanisms of HD, there is currently no cure or disease-modifying treatment available. Emerging pharmacological approaches offer promising strategies to alleviate symptoms and slow down disease progression. This comprehensive review aims to provide a critical appraisal of the latest developments in pharmacological interventions for HD. The review begins by discussing the pathogenesis of HD, focusing on the role of mutant huntingtin protein, mitochondrial dysfunction, excitotoxicity, and neuro-inflammation. It then explores emerging therapeutic targets, including the modulation of protein homeostasis, mitochondrial function, neuro-inflammation, and neurotransmitter systems. Pharmacological agents targeting these pathways are discussed, including small molecules, gene-based therapies, and neuroprotective agents. In recent years, several clinical trials have been conducted to evaluate the safety and efficiency of novel compounds for HD. This review presents an update on the outcomes of these trials, highlighting promising results and challenges encountered. Additionally, it discusses the potential of repurposing existing drugs approved for other indications as a cost-effective approach for HD treatment. The review concludes by summarizing the current state of pharmacological approaches for HD and outlining future directions in drug development. The integration of multiple therapeutic strategies, personalized medicine approaches, and combination therapies are highlighted as potential avenues to maximize treatment effectiveness.


Asunto(s)
Enfermedad de Huntington , Fármacos Neuroprotectores , Enfermedad de Huntington/tratamiento farmacológico , Humanos , Animales , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Proteína Huntingtina/genética , Proteína Huntingtina/antagonistas & inhibidores , Proteína Huntingtina/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Terapia Genética/métodos
16.
Anim Reprod Sci ; 268: 107577, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39142255

RESUMEN

The development of new strategies for breeding indigenous fish species is of utmost importance in the wake of unfavorable weather events, as a result of climate change. Therefore, an attempt has been made to achieve artificial breeding of an indigenous barb, Puntius sophore. Two groups of juvenile fish, collected from the wild, were reared till sexual maturation. One group was reared under a natural photothermal regime and the other was reared under strictly controlled conditions with photothermal stimulation till sexual maturation and subsequently, hormonal stimulation with OVAFISH was also done for inducement of spawning. The spawning efficiencies were analyzed and the results in terms of latency period (6.74 Hrs), ovulation rate (92.2 %), fertilization rate (90.6 %), hatching rate (89.9 %), and spawning efficiency coefficient (Se) (0.828) were found better in Puntius sophore reared under the indoor controlled condition with photothermal manipulation and hormone administration compared to the group of fish which was reared under a natural photothermal with a hormonal stimulation. The results of this study demonstrate the captive artificial breeding of Puntius sophore spawners reared under a natural photothermal regime and controlled photothermal regime in indoor conditions. The outcome of the present study can be used for developing key strategies for a climate smart aquaculture for fish farmers.


Asunto(s)
Cruzamiento , Animales , Femenino , Cruzamiento/métodos , Masculino , Cyprinidae/fisiología , Reproducción/fisiología , Acuicultura/métodos
17.
Curr Gene Ther ; 24(5): 377-394, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38258771

RESUMEN

Precision genome editing is a rapidly evolving field in gene therapy, allowing for the precise modification of genetic material. The CRISPR and Cas systems, particularly the CRISPRCas9 system, have revolutionized genetic research and therapeutic development by enabling precise changes like single-nucleotide substitutions, insertions, and deletions. This technology has the potential to correct disease-causing mutations at their source, allowing for the treatment of various genetic diseases. Programmable nucleases like CRISPR-Cas9, transcription activator-like effector nucleases (TALENs), and zinc finger nucleases (ZFNs) can be used to restore normal gene function, paving the way for novel therapeutic interventions. However, challenges, such as off-target effects, unintended modifications, and ethical concerns surrounding germline editing, require careful consideration and mitigation strategies. Researchers are exploring innovative solutions, such as enhanced nucleases, refined delivery methods, and improved bioinformatics tools for predicting and minimizing off-target effects. The prospects of precision genome editing in gene therapy are promising, with continued research and innovation expected to refine existing techniques and uncover new therapeutic applications.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Terapia Genética , Humanos , Terapia Genética/métodos , Terapia Genética/tendencias , Edición Génica/métodos , Edición Génica/tendencias , Nucleasas con Dedos de Zinc/genética , Nucleasas de los Efectores Tipo Activadores de la Transcripción/genética , Medicina de Precisión/métodos
18.
Ageing Res Rev ; 98: 102321, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723752

RESUMEN

Over the last three decades, neurodegenerative diseases (NDs) have increased in frequency. About 15% of the world's population suffers from NDs in some capacity, which causes cognitive and physical impairment. Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Parkinson's disease, Alzheimer's disease, and others represent a significant and growing global health challenge. Neuroinflammation is recognized to be related to all NDs, even though NDs are caused by a complex mix of genetic, environmental, and lifestyle factors. Numerous genes and pathways such as NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. In AD, the binding of Aß with CD36, TLR4, and TLR6 receptors results in activation of microglia which start to produce proinflammatory cytokines and chemokines. Consequently, the pro-inflammatory cytokines worsen and spread neuroinflammation, causing the deterioration of healthy neurons and the impairment of brain functions. Gene therapy has emerged as a promising therapeutic approach to modulate the inflammatory response in NDs, offering potential neuroprotective effects and disease-modifying benefits. This review article focuses on recent advances in gene therapy strategies targeting neuroinflammation pathways in NDs. We discussed the molecular pathways involved in neuroinflammation, highlighted key genes and proteins implicated in these processes, and reviewed the latest preclinical and clinical studies utilizing gene therapy to modulate neuroinflammatory responses. Additionally, this review addressed the prospects and challenges in translating gene therapy approaches into effective treatments for NDs.


Asunto(s)
Terapia Genética , Enfermedades Neurodegenerativas , Enfermedades Neuroinflamatorias , Humanos , Terapia Genética/métodos , Terapia Genética/tendencias , Enfermedades Neurodegenerativas/terapia , Enfermedades Neurodegenerativas/genética , Enfermedades Neuroinflamatorias/terapia , Animales
19.
Anim Reprod Sci ; 264: 107473, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626644

RESUMEN

Mola carplet (Amblypharyngodon mola) is one of the most popular small fish species of the Indian subcontinent. There are limited studies on captive breeding of this species, which is important for aquaculture and the conservation prospects of this species. The conventional induced breeding method using an inducing agent (GnRHa and dopamine antagonist) is one of the most effective and prevalent methods of breeding fish. It is a laborious and time-consuming process, particularly in mass fish breeding and in lieu of that, a less time-consuming method - sympathetic induction of the broodstock, is used in some regions of India, particularly in big carp fish. However, this method has not been reported in commercial-scale breeding of small indigenous fish species. Therefore, an experiment was conducted to compare the spawning efficiency of Amblypharyngodon mola bred by sympathetic induction with the conventional complete induced breeding method. The spawning performance in terms of latency period, relative fecundity, fertilization rate, incubation period, and hatching rates of sympathetically induced Amblypharyngodon mola were compared to completely induced Amblypharyngodon mola brooders. Although the latency period (7.8 hrs), relative fecundity (39 nos./g), fertilization rates (81.61%) and spawning efficiency coefficient (0.681) were better in conventionally induced fish, but lower post-spawning mortality (1.29%) and better hatching rates (86.21%) were observed in sympathetically induced fish. The results indicate that quality offspring of Amblypharyngodon mola could be obtained in terms of survivability through sympathetic breeding. Sympathetic induction breeding could be a cost-effective, convenient, time-saving method of mass-scale breeding and aquaculture of Amblypharyngodon mola.


Asunto(s)
Cruzamiento , Animales , Cruzamiento/métodos , Femenino , Masculino , Reproducción/fisiología
20.
Indian J Exp Biol ; 51(3): 187-200, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23678539

RESUMEN

Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases.


Asunto(s)
Encéfalo/efectos de la radiación , Teléfono Celular , Animales , Apoptosis , Biofisica/métodos , Neoplasias Encefálicas/etiología , Ciclo Celular , Línea Celular Tumoral , Sistema Nervioso Central/efectos de la radiación , Daño del ADN/efectos de la radiación , Campos Electromagnéticos , Exposición a Riesgos Ambientales , Radicales Libres , Humanos , Ratones , Modelos Biológicos , Mutágenos , Neoplasias Inducidas por Radiación/diagnóstico , Radiometría , Ratas , Especies Reactivas de Oxígeno
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