NSAIDs, SARS CoV-2 ORF Proteins, Caspases, and CARD14: Solving the Mystery of COVID-19 and Beyond

Background: Insulin resistance (IR) is a condition in which the physiological amount of insulin is insufficient to evoke a proper response of the cell, that is, glucose utilization. Metformin is the first choice for therapy, thanks to its glycemic efficacy and general tolerability. In addition, various natural compounds from plant extracts, spices, and essential oils have been shown to provide health benefits regarding insulin sensitivity. In the present study, we analyzed the effect of phospholipid derivatives of selected natural aromatic acids on insulin action and their potential use to overcome insulin resistance. Methods: The 3T3-L1 fibroblasts were differentiated into mature adipocytes; next, insulin resistance was induced by palmitic acid (16:0). Cells were further cultured with phenophospholipids at appropriate concentrations. To assess insulin sensitivity, we measured the insulin-stimulated glucose uptake, using a glucose uptake test. Results: We showed that cinnamic acid (CA) and 3-methoxycinnamic acid (3-OMe-CA) restored the proper insulin response. However, 1,2-dicinnamoyl-sn-glycero-3-phosphocholine (1,2-diCA-PC) and 1-cinnamoyl-2-palmitoyl-sn-glycero-3-phosphocholine (1-CA-2-PA-PC) improved insulin sensitivity in insulin-resistant adipocytes even stronger, exhibiting more beneficial effects. Conclusions: The binding of aromatic acids to phosphatidylcholine increases their beneficial effect on insulin sensitivity in adipocytes and expands their potential practical application as nutraceutical health-promoting agents.

Download Full-text

Topical Tacrolimus for Psoriasis

The Open Allergy Journal ◽

10.2174/1874838400902010051 ◽

2009 ◽

Vol 2 (1) ◽

pp. 51-55 ◽

Cited By ~ 2

Author(s):

Toshiyuki Yamamoto

Keyword(s):

Atopic Dermatitis ◽

Recent Progress ◽

Therapeutic Strategies ◽

Skin Atrophy ◽

Topical Tacrolimus ◽

Beneficial Effects ◽

First Choice ◽

Short Period ◽

Tacrolimus Therapy ◽

Genital Psoriasis

Tacrolimus ointment is an agent approved for the treatment of atopic dermatitis; however, tacrolimus has been expected also as one of the promising therapeutic strategies for other T-cell mediated inflammatory skin disorders. Recent progress have demonstrated that topical tacrolimus shows beneficial effects for psoriasis depending on sites. In particular, facial, intertriginous, and genital psoriasis respond to topical tacrolimus dramatically in a short period. Further, topical tacrolimus is tolerable also for child psoriasis. Because topical tacrolimus does not induce either skin atrophy or telangiectasia different from corticosteroids, it is recommended to be a first choice. The most proper way of topical tacrolimus therapy at present is to use this ointment intermittently after the remission was once obtained, paying attention to its adverse effects.

Download Full-text

Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

Biomedicines ◽

10.3390/biomedicines9010003 ◽

2020 ◽

Vol 9 (1) ◽

pp. 3

Author(s):

Teresa Salvatore ◽

Pia Clara Pafundi ◽

Raffaele Galiero ◽

Luca Rinaldi ◽

Alfredo Caturano ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Clinical Evidence ◽

Polyol Pathway ◽

Cardiovascular Complications ◽

Diabetic Patients ◽

Beneficial Effects ◽

Kinase C ◽

First Choice ◽

Glycation End Products

Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.

Download Full-text

NSAIDs Immunomodulation in COVID-19 Might Inhibit SARS CoV-2 ORF Proteins Induced Caspase Activation, Necroptosis and Endoplasmic Reticulum Stress.

10.22541/au.162126663.38675715/v1 ◽

2021 ◽

Author(s):

Mina Kelleni

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Caspase Activation ◽

Caspase Inhibitors ◽

Caspase Recruitment Domain ◽

Signaling Mechanisms ◽

First Choice ◽

Potential Benefits ◽

One Year

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.

Download Full-text

Solid Lipid Nanoparticles: An Approach to Improve Oral Drug Delivery

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps31788 ◽

2021 ◽

Vol 24 ◽

pp. 509-532

Author(s):

Nestor Mendoza-Muñoz ◽

Zaida Urbán-Morlán ◽

Gerardo Leyva-Gómez ◽

María de la Luz Zambrano-Zaragoza ◽

Elizabeth ¨Piñón-Segundo ◽

...

Keyword(s):

Oral Administration ◽

Solid Lipid Nanoparticles ◽

Oral Drug Delivery ◽

Neurological Diseases ◽

Lipid Nanoparticles ◽

Oral Drug ◽

Beneficial Effects ◽

Solid Lipid ◽

First Choice ◽

Poorly Soluble

Nanoparticles have shown overall beneficial effects in drug administration. Specifically, solid lipid nanoparticles (SLN) have emerged as an alternative to polymer-based systems. However, the oral administration of SLN, the first choice for conventional medications, has not been addressed due to the taboo surrounding the complicated transit that this delivery route entails. This review focuses on the encapsulation of drugs into SLN as a strategy for improving oral administration. Examples of applications of SLN to enhance the absorption and bioavailability of poorly-soluble drugs and protect acid-labile active molecules are discussed. This work also emphasizes the importance of developing SLN-based systems to treat health issues such as neurological diseases and cancer, and combat antibiotic resistance, three significant and increasingly common current public health problems. The review sections clarify how SLN can improve bioavailability, target therapeutic agents, and reduce side effects.

Download Full-text

The Effects of Chunghyul-Dan, an Agent of Korean Medicine, on a Mouse Model of Traumatic Brain Injury

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7326107 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Won-Woo Choi ◽

Kyungjin Lee ◽

Beom-Joon Lee ◽

Seong-Uk Park ◽

Jung-Mi Park ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mouse Model ◽

Brain Edema ◽

Brain Damage ◽

Motor Deficits ◽

Pharmacological Effects ◽

Beneficial Effects ◽

First Choice ◽

Prevention And Treatment

Chunghyul-Dan (CHD) is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI) mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB) damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.

Download Full-text

NSAIDs Immunomodulation in COVID-19 Might Inhibit SARS CoV-2 ORF Proteins Induced Caspase Activation, Necroptosis and Endoplasmic Reticulum Stress.

10.22541/au.162126663.38675715/v4 ◽

2021 ◽

Author(s):

Mina Kelleni

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Mitochondrial Dysfunction ◽

Caspase Activation ◽

Caspase Inhibitors ◽

Caspase Recruitment Domain ◽

Signaling Mechanisms ◽

First Choice ◽

Potential Benefits ◽

One Year

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.

Download Full-text

The Possible Protective Effect of Metformin in COVID-19 Infection

Journal of Advances in Medical and Pharmaceutical Sciences ◽

10.9734/jamps/2020/v22i830185 ◽

2020 ◽

pp. 1-5

Author(s):

Waleed K. Abdulsahib

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Converting Enzyme ◽

Obese Women ◽

Women Patients ◽

Angiotensin Converting Enzyme 2 ◽

Beneficial Effects ◽

First Choice

Coronavirus 2019 (COVID-19) infections with more than 30 million confirmed cases are increasing rapidly, requiring urgent and safe treatment. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus responsible for the infection of COVID-19. Metformin (M) is a biguanide drug used as a first choice for the management of hyperglycemia in type 2 diabetes mellitus (T2DM). Furthermore, it is safe and currently available. It is speculated that metformin can be used for T2DM patients with COVID-19, because in addition to its hypoglycemic effect, this biguanide also shows many beneficial effects, including anti-inflammatory effects and cardiopulmonary protection especially by angiotensin converting enzyme 2 (ACE2) targeting. Therefore, the reasons for the use of metformin in COVID-19 patients were discussed in this study. Metformin has a promising role in treatment of COVID-19 in T2DM and obese women patients.

Download Full-text

Physiological and Histological Study for the Effect of Escalation Doses of Dostinex (Caprigoline) on Male Mice through Some Biochemical Parameters

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2016.10.1.459 ◽

2016 ◽

Vol 10 (1) ◽

pp. 42-47

Author(s):

Shaima R. Ibraheem

Keyword(s):

Morphological Changes ◽

Histological Study ◽

Inflammatory Cells ◽

High Dose ◽

Male Mice ◽

Beneficial Effects ◽

First Choice ◽

Liver And Kidney ◽

History Of ◽

Hormonal Assay

Although the history of many drugs proved some beneficial effects, yet uncontrolled use may have serious impact on health especially vital organs as liver and kidney and endocrine glands. Dopamine agonists are the treatment of choice for the majority of patients with hyperprolactinemic disorders. Bromocriptine has been used over the past 30 years, whereas cabergoline has become a first-choice agonist in recent years. The present study was aimed to evaluate the physiological and histological effects of escalated doses of the drug (Caprigoline) in male mice. The experiment includes 40 mice divided on 4 groups. Group 1 treated with PBS represents the control. The groups (2, 3, and 4) treated with the doses (0.5, 5, and 10) mg of caprigoline /Kg body weight respectively. Regarding hormonal assay, the results showed significant (P<0.05) differences between the treated groups and the control. There was a significant increase in luteinizing hormone (LH), testosterone, Triiodothyronine (T3) and Throxine (T4) level accompanies the increase in caprigoline dose. In contrast the Follicle stimulating hormone (FSH) and prolactin (PRL) show a decrease in their levels as the dose become higher. Furthermore; there was a significant increase in level of Alanin aminotransaminase (ALT) as an indicator of liver function and a significant increase in level of urea as an indicator of kidney function in the treated groups compared with the control. The histological study reveal an obvious morphological changes compared with the normal state in the animals treated with the high dose. The liver in mice treated with (5 and 10) mg caprigoline showing focal area of necrosis with inflammatory cells. The kidney in mice treated with 10 mg caprigoline shows a degenerative changes and necrosis of epithelial of micro tubules and thyroidization phenomeno.

Download Full-text

Rating enrichment items by group-housed laboratory mice in multiple binary choice tests using an RFID-based tracking system

10.1101/2021.10.20.465117 ◽

2021 ◽

Author(s):

Ute Hobbiesiefken ◽

Birk Urmersbach ◽

Anne Jaap ◽

Kai Diederich ◽

Lars Lewejohann

Keyword(s):

Tracking System ◽

Point Of View ◽

Laboratory Animals ◽

Housing Conditions ◽

Laboratory Mice ◽

Beneficial Effects ◽

Positive Effects ◽

Cage System ◽

First Choice ◽

Experimental Apparatus

There is a growing body of evidence that enrichment of the housing conditions of laboratory animals has positive effects on daily behavior, growth, and health. Laboratory mice spend most of their lives in their housing rather than in experimental apparatus, so improving housing conditions is a first-choice approach to improving their welfare. Despite the increasing popularity of enrichment, little is known about whether it is also perceived as being beneficial from the animal's point of view. This is especially true due to the fact that enrichment has become an umbrella term that encompasses a wide variety of different elements. We categorized enrichment items according to their prospective use into the categories structural, housing, and foraging and let female C57BL/6J mice chose within the categories according to their preference. Preferences were tested over a 46-hour period in a home cage system consisting of two interconnected cages equipped with the respective items to be compared. A new analysing method combined binary decisions and ranked the enrichment items within each category by calculating worth values. The assignment of worth values to the items to be compared led to a further gain in information, estimating importance from the mice's point of view in addition to pure ranking. Given the known beneficial effects of enrichment, these data will help in deciding how to provide appropriate enrichment elements to improve animal welfare and refine animal experimentation.

Download Full-text