Prenatal Hyperglycemia Exposure and Cellular Stress, a Sugar-Coated View of Early Programming of Metabolic Diseases

Worldwide, the number of people with diabetes has quadrupled since 1980 reaching 422 million in 2014 (World Health Organization). This distressing rise in diabetes also affects pregnant women and thus, in regard to early programming of adult diseases, creates a vicious cycle of metabolic dysfunction passed from one generation to another. Metabolic diseases are complex and caused by the interplay between genetic and environmental factors. High-glucose exposure during in utero development, as observed with gestational diabetes mellitus (GDM), is an established risk factor for metabolic diseases. Despite intense efforts to better understand this phenomenon of early memory little is known about the molecular mechanisms associating early exposure to long-term diseases risk. However, evidence promotes glucose associated oxidative stress as one of the molecular mechanisms able to influence susceptibility to metabolic diseases. Thus, we decided here to further explore the relationship between early glucose exposure and cellular stress in the context of early development, and focus on the concept of glycemic memory, its consequences, and sexual dimorphic and epigenetic aspects.

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Natural products from the traditional Moroccan pharmacopoeia: A potential lead for the prevention and treatment of COVID-19

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3619 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 1278-1285

Author(s):

Mohamed Yafout ◽

Amine Ousaid ◽

Ibrahim Sbai El Otmani ◽

Youssef Khayati ◽

Amal Ait Haj Said

Keyword(s):

Medicinal Plants ◽

Plant Extracts ◽

Molecular Mechanisms ◽

Scientific Literature ◽

Treatment Protocol ◽

World Health ◽

The World ◽

Health Organization ◽

Promising Source

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.

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Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00454-7 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Yuefei Jin ◽

Wangquan Ji ◽

Haiyan Yang ◽

Shuaiyin Chen ◽

Weiguo Zhang ◽

...

Keyword(s):

Molecular Mechanisms ◽

Endothelial Activation ◽

World Health ◽

Therapeutic Approaches ◽

Inflammatory Reactions ◽

Angiotensin Converting Enzyme 2 ◽

Therapeutic Implications ◽

Endothelial Inflammation ◽

The World ◽

Health Organization

AbstractOn 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients. Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation. Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier, promoting pro-coagulative state, inducing endothelial inflammation, and even mediating leukocyte infiltration. This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.

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The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

Viruses ◽

10.3390/v13071346 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1346

Author(s):

Priya Veluswamy ◽

Max Wacker ◽

Dimitrios Stavridis ◽

Thomas Reichel ◽

Hendrik Schmidt ◽

...

Keyword(s):

Molecular Mechanisms ◽

Immune Cell ◽

Cardiovascular Complications ◽

World Health ◽

Endothelial Glycocalyx ◽

Pathological State ◽

Mediated Action ◽

Cell Responses ◽

Health Organization

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.

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Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress

Cellular and Molecular Life Sciences ◽

10.1007/s00018-020-03566-z ◽

2020 ◽

Vol 77 (23) ◽

pp. 4861-4898

Author(s):

Efthimia R. Christoforou ◽

Amanda N. Sferruzzi-Perri

Keyword(s):

Molecular Mechanisms ◽

Metabolic Diseases ◽

Developmental Programming ◽

In Utero ◽

Postnatal Life ◽

Molecular Pathways ◽

Epigenetic Mechanisms ◽

Metabolic Dysfunction ◽

Rodent Models ◽

Human Lifespan

Abstract The results of different human epidemiological datasets provided the impetus to introduce the now commonly accepted theory coined as ‘developmental programming’, whereby the presence of a stressor during gestation predisposes the growing fetus to develop diseases, such as metabolic dysfunction in later postnatal life. However, in a clinical setting, human lifespan and inaccessibility to tissue for analysis are major limitations to study the molecular mechanisms governing developmental programming. Subsequently, studies using animal models have proved indispensable to the identification of key molecular pathways and epigenetic mechanisms that are dysregulated in metabolic organs of the fetus and adult programmed due to an adverse gestational environment. Rodents such as mice and rats are the most used experimental animals in the study of developmental programming. This review summarises the molecular pathways and epigenetic mechanisms influencing alterations in metabolic tissues of rodent offspring exposed to in utero stress and subsequently programmed for metabolic dysfunction. By comparing molecular mechanisms in a variety of rodent models of in utero stress, we hope to summarise common themes and pathways governing later metabolic dysfunction in the offspring whilst identifying reasons for incongruencies between models so to inform future work. With the continued use and refinement of such models of developmental programming, the scientific community may gain the knowledge required for the targeted treatment of metabolic diseases that have intrauterine origins.

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The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation

International Journal of Molecular Sciences ◽

10.3390/ijms19102968 ◽

2018 ◽

Vol 19 (10) ◽

pp. 2968 ◽

Cited By ~ 18

Author(s):

Albino Carrizzo ◽

Carmine Izzo ◽

Marco Oliveti ◽

Antonia Alfano ◽

Nicola Virtuoso ◽

...

Keyword(s):

Diabetes Mellitus ◽

Endothelial Dysfunction ◽

Molecular Mechanisms ◽

Vascular Complications ◽

World Health ◽

Northern Europe ◽

Common Disease ◽

Main Determinants ◽

Health Organization ◽

Platelet Hyperaggregation

Diabetes mellitus is a common disease that affects 3–5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6–8% of the population. Of great concern is that the number of cases of diabetes is constantly increasing, probably due to the increase in obesity and the sedentary nature of the population. According to the World Health Organization, in the year 2030 there will be 360 million people with diabetes, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on health systems that offer assistance to patients. In this review, we try to describe in an organized way the pathophysiological continuity between diabetes mellitus, endothelial dysfunction, and platelet hyperaggregation, highlighting the main molecular mechanisms involved and the interconnections.

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Detection of a novel mutation G511T in the 530 loop in 16S rRNA in multi drugs resistant Mycobacterium tuberculosis isolated from Sudanese patients

10.1101/497628 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yousif Mohammed Alfatih ◽

Abeer Babiker Idris ◽

Hadeel Gassim Hassan ◽

Eman O M Nour ◽

Nihad M A Elhaj ◽

...

Keyword(s):

16S Rrna ◽

Molecular Mechanisms ◽

Novel Mutation ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

World Health ◽

Bacterial Disease ◽

Global Public Health ◽

Mdr Tb ◽

Health Organization

Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system. Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach. Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools. Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop. Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.

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The history and epidemiology of Middle East respiratory syndrome corona virus

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2017.246 ◽

2017 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Aisha M. Al-Osail ◽

Marwan J. Al-Wazzah

Keyword(s):

Middle East ◽

Molecular Mechanisms ◽

Middle Eastern ◽

Middle East Respiratory Syndrome ◽

World Health ◽

Corona Virus ◽

Control And Prevention ◽

Novel Virus ◽

Health Organization ◽

Corona Viruses

Corona viruses cause common cold, and infections caused by corona viruses are generally self-resolving. During the last 4 years, corona viruses have become the most important viruses worldwide because of the occurrence of several recent deaths caused by corona viruses in Saudi Arabia. Spread of the infection occurred worldwide; however, most cases of mortality have occurred in the Middle East. Owing to the predominance of outbreaks in the Middle Eastern countries, the virus was renamed a Middle East respiratory syndrome corona virus (MERS-CoV) by the Corona virus Study Group. The Center for Diseases Control and Prevention and World Health Organization maintain a website that is updated frequently with new cases of MERS-CoV infection. In this review, we describe the history and epidemiology of this novel virus. Studies of the genetics and molecular mechanisms of this virus are expected to facilitate the development of vaccines in the future.

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An Update on Silent Corticotroph Adenomas: Diagnosis, Mechanisms, Clinical Features, and Management

Cancers ◽

10.3390/cancers13236134 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6134

Author(s):

Shenzhong Jiang ◽

Xiaokun Chen ◽

Yinzi Wu ◽

Renzhi Wang ◽

Xinjie Bao

Keyword(s):

Clinical Features ◽

Molecular Mechanisms ◽

Early Recognition ◽

World Health ◽

Pituitary Hormone ◽

Endocrine Tumors ◽

Tissue Samples ◽

Management Approaches ◽

Health Organization ◽

Corticotroph Adenomas

With the introduction of 2017 World Health Organization (WHO) classification of endocrine tumors, T-PIT can serve as a complementary tool for identification of silent corticotroph adenomas (SCAs) in some cases if the tumor is not classifiable by pituitary hormone expression in pathological tissue samples. An increase of the proportion of SCAs among the non-functioning pituitary adenomas (NFPAs) has been witnessed under the new rule with the detection of T-PIT-positive ACTH-negative SCAs. Studies of molecular mechanisms related to SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. A precise pathological diagnosis can help clinicians better identify SCAs. Understanding clinical features in the context of the pathophysiology of SCAs is critical for optimal management. It could provide information on appropriate follow-up time and aid in early recognition and treatment of potentially aggressive forms. Management approaches include surgical, radiation, and/or medical therapies.

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Drug-Resistant Tuberculosis 2020: Where We Stand

Applied Sciences ◽

10.3390/app10062153 ◽

2020 ◽

Vol 10 (6) ◽

pp. 2153 ◽

Cited By ~ 1

Author(s):

Angelo Iacobino ◽

Lanfranco Fattorini ◽

Federico Giannoni

Keyword(s):

Molecular Mechanisms ◽

Drug Distribution ◽

Multidrug Resistant ◽

Diagnostic Methods ◽

World Health ◽

Drug Resistant ◽

Comprehensive Overview ◽

Resistant Tuberculosis ◽

Health Organization ◽

Incident Cases

The control of tuberculosis (TB) is hampered by the emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, defined as resistant to at least isoniazid and rifampin, the two bactericidal drugs essential for the treatment of the disease. Due to the worldwide estimate of almost half a million incident cases of MDR/rifampin-resistant TB, it is important to continuously update the knowledge on the mechanisms involved in the development of this phenomenon. Clinical, biological and microbiological reasons account for the generation of resistance, including: (i) nonadherence of patients to their therapy, and/or errors of physicians in therapy management, (ii) complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, resulting in resistance development, (iii) intrinsic drug resistance of tubercle bacilli, (iv) formation of non-replicating, drug-tolerant bacilli inside the granulomas, (v) development of mutations in Mtb genes, which are the most important molecular mechanisms of resistance. This review provides a comprehensive overview of these issues, and releases up-dated information on the therapeutic strategies recently endorsed and recommended by the World Health Organization to facilitate the clinical and microbiological management of drug-resistant TB at the global level, with attention also to the most recent diagnostic methods.

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