Multimodal action of phosphodiesterase 5 inhibitors against neurodegenerative disorders: An update review.

Phosphodiesterase type 5 (PDE5) is an enzyme primarily found in the smooth muscle of the corpus cavernosum and also highly expressed in the substantia nigra, cerebellum, caudate, hippocampal regions and cerebellar purkinje cells, responsible for selectively breaking down cyclic guanosine monophosphate (cGMP) into 5'-GMP and regulate intracellular cGMP levels. As a second messenger, cyclic GMP enhances signals at postsynaptic receptors and triggers downstream effector molecules, leading to changes in gene expression and neuronal responses. Additionally, cGMP signaling transduction cascade, present in the brain, is also essential for learning and memory processes. Mechanistically, PDE5 inhibitors share structural similarities with cGMP, competitively binding to PDE5 and inhibiting cGMP hydrolysis. This action enhances the effects of nitric oxide, resulting in anti-inflammatory and neuroprotective effects. Neurodegenerative disorders entail the progressive loss of neuron structure, culminating in neuronal cell death, with currently available drugs providing only limited symptomatic relief, rendering neurodegeneration considered incurable. PDE5 inhibitors have recently emerged as a potential therapeutic approach for neurodegeneration, neuroinflammation, and diseases involving cognitive impairment. This review elucidates the principal roles of 3',5'-cyclic adenosine monophosphate (cAMP) and cGMP signaling pathways in neuronal functions, believed to play pivotal roles in the pathogenesis of various neurodegenerative disorders. It provides an updated assessment of PDE5 inhibitors as disease-modifying agents for conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral ischemia, Huntington's disease, and neuroinflammation. The paper aims to review the current understanding of PDE5 inhibitors, which concurrently regulate both cAMP and cGMP signaling pathways, positing that they may exert complementary and synergistic effects in modifying neurodegeneration, thus presenting a novel direction in therapeutic discovery. Moreover, the review provides critical about biological functions, therapeutic potentials, limitations, challenges, and emerging applications of selective PDE5 inhibitors. This comprehensive overview aims to guide future academic and industrial endeavors in this field.

Nerolidol- Potential Therapeutic Agent for Various Neurological Disorders via its Antioxidative Property.

Neurological disorders are devastating conditions affecting both cognitive and motorrelated functions in aged people. Yet there is no proper medication to treat these illnesses, and the currently available medications can only provide symptomatic relief to the patients. All neurological disorders share the same etiology, such as oxidative stress, mitochondrial dysfunction, neurochemical deficiency, neuronal loss, apoptosis, endoplasmic reticulum stress, neuroinflammation, and disease-related protein aggregation. Nowadays, researchers use antioxidant-based strategies to prevent or halt the disease progression. Nerolidol, a strong antioxidant, possesses various biological activities and properties that treat cardiotoxicity, nephrotoxicity, neurotoxicity, and many other diseases. Many recent publications and research studies highlight the beneficial effect of nerolidol on brain disorders. In Alzheimer's disease, nerolidol shows neuroprotection by decreasing amyloid plaque formation, lipid peroxidation, cholinergic neuronal loss, locomotor dysfunction, neuroinflammation, and hippocampal damage via enhancing antioxidant expression. Also, it shows neuroprotection against rotenone-induced neurotoxicity by inhibiting microglial activation. Another study reported that nerolidol shows antiepileptic effects in animal models by suppressing kindling-induced memory impairment by decreasing oxidative stress. It has been found that NRL administration increases the antioxidant levels, decreasing the proinflammatory cytokine release as well as decreasing the apoptotic protein and cerebral infarct size. In conclusion, nerolidol tends to reverse the harmful effects of disease-related factors, including OS, neuroinflammation, protein aggregation, and apoptosis, making nerolidol a choiceable drug for the management of neurological disorders. The purpose of this review is to discuss the mechanism of nerolidol in treating various neurological disorders.

Cracking the Code of Lumpy Skin Disease: Identifying Causes, Symptoms and Treatment Options for Livestock Farmers.

The novel bovine viral infection known as lumpy skin disease is common in most African and Middle Eastern countries, with a significant likelihood of disease transfer to Asia and Europe. Recent rapid disease spread in formerly disease-free zones highlights the need of understanding disease limits and distribution mechanisms. Capripox virus, the causal agent, may also cause sheeppox and Goatpox. Even though the virus is expelled through several bodily fluids and excretions, the most common causes of infection include sperm and skin sores. Thus, vulnerable hosts are mostly infected mechanically by hematophagous arthropods such as biting flies, mosquitoes, and ticks. As a result, milk production lowers, abortions, permanent or temporary sterility, hide damage, and mortality occur, contributing to a massive financial loss for countries that raise cattle. These illnesses are economically significant because they affect international trade. The spread of Capripox viruses appears to be spreading because to a lack of effectual vaccinations and poverty in rural areas. Lumpy skin disease has reached historic levels; as a consequence, vaccination remains the only viable option to keep the illness from spreading in endemic as well as newly impacted areas. This study is intended to offer a full update on existing knowledge of the disease's pathological characteristics, mechanisms of spread, transmission, control measures, and available vaccinations.

The Impacts and Changes Related to the Cancer Drug Resistance Mechanism.

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Aminophenyl-substituted cobalt(iii) corrole: a bifunctional electrocatalyst for the oxygen and hydrogen evolution reactions.

Catalytic water splitting is a highly promising area of research for the development of a hydrogen-based society. Herein, the synthesis of the bifunctional A2B-type cobalt(iii) corrole Co(BAPC)Py2 having the electron-withdrawing meso-pentafluorophenyl and the basic meso-p-aminophenyl substituents is reported. Cyclic voltammetric studies reveal that Co(BAPC)Py2 has two oxidation waves at 0.97 V and 1.42 V associated with the Co(iii) → Co(iv) and Co(iv) → Co(v) redox couples, respectively, and two reduction waves at 0.45 and -0.21 V corresponding to the Co(iii) → Co(ii) and Co(ii) → Co(i) redox couples. The as-synthesized Co(BAPC)Py2 corrole has been demonstrated to be an efficient catalyst for the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) in homogeneous (acetonitrile) as well as heterogeneous media. In a homogeneous solution, Co(BAPC)Py2 showed excellent activity towards both the HER, with the first-order rate constant (kcat) of 952.0 s-1, and the OER with the first-order rate constant of 0.2 s-1. The strong electron -withdrawing pentafluorophenyl group present on the corrole ring shifts the redox process towards the anodic direction and facilitates the HER performance, whereas the aminophenyl group increases the basicity of the catalyst that improves the OER activity.

Extremophilic micro-algae and their potential contribution in biotechnology.

Micro-algae have potential as sustainable sources of energy and products and alternative mode of agriculture. However, their mass cultivation is challenging due to low survival under harsh outdoor conditions and competition from other, undesired, species. Extremophilic micro-algae have a role to play by virtue of their ability to grow under acidic or alkaline pH, high temperature, light, CO2 level and metal concentration. In this review, we provide several examples of potential biotechnological applications of extremophilic micro-algae and the ranges of tolerated extremes. We also discuss the adaptive mechanisms of tolerance to these extremes. Analysis of phylogenetic relationship of the reported extremophiles suggests certain groups of the Kingdom Protista to be more tolerant to extremophilic conditions than other taxa. While extremophilic microalgae are beginning to be explored, much needs to be done in terms of the physiology, molecular biology, metabolic engineering and outdoor cultivation trials before their true potential is realized.