scholarly journals Molecular Mechanisms of Possible Action of Naphthoquinones from Onosma in the Treatment and Prevention of COVID-19

Author(s):  
Namık KILINÇ
2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.


2015 ◽  
Vol 309 (10) ◽  
pp. F821-F834 ◽  
Author(s):  
Pinelopi P. Kapitsinou ◽  
Volker H. Haase

More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review.


2021 ◽  
pp. 1200-1208
Author(s):  
С. В. Булгакова ◽  
Е. В. Тренева ◽  
Н. О. Захарова ◽  
А. В. Николаева

Препараты кальция входят в схемы лечения и профилактики низкой минеральной плотности костной ткани. Однако последние научные исследования показали, что дополнительное поступление кальция может увеличить риск сердечно-сосудистых заболеваний. Это связано с отложением кальция в эндотелии кровеносных сосудов. Значимость минерализации сосудистой стенки не ограничивается локальным накоплением кальциевых депозитов, но в значительной мере определяется их активирующим влиянием на прогрессирование атеросклероза. Витамин К играет важную роль в гомеостазе кальция, снижает артериальную кальцификацию и артериальную жесткость и, как следствие, оказывает протективный эффект при приеме кальция. В данном обзоре литературы представлена современная информация о кальциевом парадоксе, обсуждаются основные молекулярные механизмы кальцификации сосудов, рассмотрены терапевтические стратегии лечения витамином К . Calcium preparations are included in the treatment and prevention regimens for low bone mineral density. However, recent scientific studies have shown that additional calcium intake can increase the risk of heart disease, which is associated with the deposition of calcium in the endothelium of blood vessels. The significance of vascular wall mineralization is not limited to local accumulation of calcium deposits, but is largely determined by their activating effect on the progression of atherosclerosis. Vitamin K plays an important role in calcium homeostasis, reduces arterial calcification and arterial stiffness and, as a result, has a protective effect when taking calcium. This literature review provides current information about the calcium paradox, discusses the main molecular mechanisms of vascular calcification, and considers therapeutic strategies for vitamin К treatment.


Author(s):  
H. Hampel ◽  
S.E. O’Bryant ◽  
J.I. Castrillo ◽  
C. Ritchie ◽  
K. Rojkova ◽  
...  

During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer’s disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical “one-size-fits-all” approach in drug discovery towards biomarker guided “molecularly” tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.


2021 ◽  
Vol 915 (1) ◽  
pp. 012032
Author(s):  
A Ishchenko ◽  
N Stuchynska ◽  
L Haiova ◽  
E Shchepanskiy

Abstract The aim of the article is to carry out a systematic analysis of the components of chemical safety in the context of the environmental aspect of sustainable development goals and to identify those components with the help of competent health professionals. Hazardous chemicals can travel for long distances, be accumulated in the environment as well as cause adverse effects on human health through food chains. The action of toxicants of inorganic and organic nature occurs due to the violation of metabolic processes, inhibition of enzymes, and biotransformation of xenobiotics into more toxic compounds. Physicians must be clearly aware of the relationship in the “toxicant-pathology” system; understand the molecular mechanisms of the hazardous chemicals action; use terminology regarding toxicological characteristics of toxicants; conduct educational, treatment, and prevention activities among the population; acquire information on regulations governing the management of chemical compounds. The next component of chemical safety is the knowledge of approaches to chemical labeling and safety measures for working with chemical products throughout their life cycle. Proper interpretation of the type and level of hazard will enable taking necessary precautions and following relevant safety rules while working with chemical products.


ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110375
Author(s):  
Zhong-Qi Bu ◽  
Hai-Yang Yu ◽  
Jue Wang ◽  
Xin He ◽  
Yue-Ran Cui ◽  
...  

Ischemic stroke is one of the main causes of high morbidity, mortality, and disability worldwide; however, the treatment methods are limited and do not always achieve satisfactory results. The pathogenesis of ischemic stroke is complex, defined by multiple mechanisms; among them, programmed death of neuronal cells plays a significant role. Ferroptosis is a novel type of regulated cell death characterized by iron redistribution or accumulation and increased lipid peroxidation in the membrane. Ferroptosis is implicated in many pathological conditions, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. In this review, we summarize current research findings on ferroptosis, including possible molecular mechanisms and therapeutic applications of ferroptosis regulators, with a focus on the involvement of ferroptosis in the pathogenesis and treatment of ischemic stroke. Understanding the role of ferroptosis in ischemic stroke will throw some light on the development of methods for diagnosis, treatment, and prevention of this devastating disease.


2020 ◽  
Vol 8 (10) ◽  
Author(s):  
Nathan Roberts ◽  
Robert Brown ◽  
L. Buja ◽  
Priya Weerasinghe

Turmeric (Curcuma Longa) has a near 4000-year history of extensive medical use in South Asia. Its main physiologically active phytochemical is curcumin (diferuloylmethane), derived from the rhizome of turmeric. Curcumin is a hydrophobic polyphenol with a diketone moiety connecting two phenoxy rings. It is widely available, and exerts systemic and pleiotropic effects via several key mechanisms. Most famously, it is known to inhibit pro-inflammatory pathways such as PI3k/akt/NF-kB activation. It is also a potent antioxidant and free radical scavenger via a sequential proton loss electron transfer mechanism in ionizing solvents due to its extended conjugating ability across the entire molecule, and its ability to induce NRF-2. It has been implicated in the treatment of diseases ranging from asthma to various cancers, and is also a broad spectrum anti-microbial. COVID-19 is a novel beta-coronavirus that was declared a pandemic by the WHO in March, 2020. It is primarily a respiratory disorder, but it can spread hematogenously and effect many other organs such as the heart, nervous system, and kidneys. There is a significant intersection between the clinical manifestations of COVID-19 and curcumin’s therapeutic effects. In addition, curcumin has been shown to inhibit initial viral infectivity. Thus, there is potential for curcumin to safely both prevent and treat COVID-19 infection across the globe.


2021 ◽  
Vol 22 (15) ◽  
pp. 7775
Author(s):  
Ana Paredes ◽  
Rocio Santos-Clemente ◽  
Mercedes Ricote

The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Daniela Gradinaru ◽  
Anca Ungurianu ◽  
Denisa Margina ◽  
Maria Moreno-Villanueva ◽  
Alexander Bürkle

Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an “anti-aging” molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a “veteran” drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database.


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