Chemically modified mRNA beyond COVID-19: Potential preventive and therapeutic applications for targeting chronic diseases

Chemically modified mRNA represents a unique, efficient, and straightforward approach to produce a class of biopharmaceutical agents. It has been already approved as a vaccination-based method for targeting SARS-CoV-2 virus. The COVID-19 pandemic has highlighted the prospect of synthetic modified mRNA to efficiently and safely combat various diseases. Recently, various optimization advances have been adopted to overcome the limitations associated with conventional gene therapeutics leading to wide-ranging applications in different disease conditions. This review sheds light on emerging directions of chemically modified mRNAs to prevent and treat widespread chronic diseases, including metabolic disorders, cancer vaccination and immunotherapy, musculoskeletal disorders, respiratory conditions, cardiovascular diseases, and liver diseases.Qatar University (Grant # QUCG-CPH-20/21-4 and QUCG-CPH-21/22-1

Exploring QU health students' behavioral determinants, perspectives, and experiences toward student leadership: A quantitative study

Objective: Leadership is an essential part of student's learning experience in the college. The main aim of this study is to determine and explore QU health student's perspectives and experiences toward leadership. Methods: A cross-sectional study was conducted during the academic year 2021. A web-based questionnaire was circulated to 1352 QU health students. Participants were asked to complete a 5-point Likert scale developed using theoretical domains framework (TDF) to identify their perception and behavioral determinants about leadership. They were also asked to rank the importance of personal, interpersonal capabilities, and markers of success of leadership. Participants were asked to answer open- ended questions to determine the training and support needed for leadership. Results: In total, 179 complete responses were collected. About (43.6%) of students strongly agreed that it is crucial for healthcare students to be involved in leadership. Most students agreed that they are capable of carrying leadership responsibilities. Around 71.4% of leaders in QU health perceived that teaching quality improvement as very important to extremely important marker of leader's success. Students identified that negotiation and communication are important skills for leadership. Conclusion: Our study suggests that QU health students perceive leadership as positive and important experience of college life and show high interest for training programs and workshops for student leaders

Ethanol-Based Proliposomes Incorporating Dexamethasone for The Treatment of COVID-19 Acute Respiratory Distress Syndrome (ARDS) Using Medical Nebulizers

Background/Objective: Systemic dexamethasone has demonstrated mortality reduction in COVID-19-related acute respiratory distress syndrome (ARDS). The aim of this study is to use ethanol-based proliposome technology to formulate inhalable liposomes encapsulating dexamethasone for localized anti-inflammatory effect in the lung. Methods: Ethanol-based proliposomes were prepared using equimolar ratios of cholesterol and one of three phospholipids: soya-phosphatidylcholine(SPC), hydrogenated SPC(HSPC), or dipalmitoyl-phosphatidylcholine(DPPC). Hydration of proliposomes was followed by probe-sonication to generate small unilamellar vesicles (SUVs), then followed by the determination of particle size, zeta-potential, entrapment efficiency, and drug release. Aerosol characterization studies were performed using three different nebulizers (air-jet, ultrasonic, and mesh) delivered to a two-stage impinger. Finally, cytokine release was measured in peripheral blood mononuclear cells stimulated with lipopolysaccharide and treated with the formulation. Results: The prepared SUVs had particle size <100 nm, polydispersity index (PDI) <0.3, and slightly negative zeta-potential. SPC liposomes had significantly (pvalue< 0.05) lower particle size and PDI compared to HSPC and DPPC liposomes, and entrapped significantly more dexamethasone (p-value<0.05). The air-jet nebulizer was the superior nebulizer in terms of mass, drug, and lipid output and fine particle fraction, and was the least physically disruptive to liposomes. All three formulations were successfully delivered using the air-jet nebulizer; however, SPC liposomes had significantly higher drug output rate, respirable dose, and underwent less aggregation. Cytokine release studies demonstrated that liposomal dexamethasone suppressed cytokine release in a manner superior to free dexamethasone. Conclusion: SUVs with small particle size and low PDI were successfully prepared and delivered using different nebulizers. Of the three investigated formulations, SPC liposomes delivered using the air-jet nebulizer are the most promising for further development. Future studies will be dedicated to scaling up this formulation and testing it using in vivo models of acute lung injury

Mol Biol Rep

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings

Mol Biol Rep

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings

Unlocking the secrets: exploring the influence of the aryl hydrocarbon receptor and microbiome on cancer development

Abstract Gut microbiota regulates various aspects of human physiology by producing metabolites, metabolizing enzymes, and toxins. Many studies have linked microbiota with human health and altered microbiome configurations with the occurrence of several diseases, including cancer. Accumulating evidence suggests that the microbiome can influence the initiation and progression of several cancers. Moreover, some microbiotas of the gut and oral cavity have been reported to infect tumors, initiate metastasis, and promote the spread of cancer to distant organs, thereby influencing the clinical outcome of cancer patients. The gut microbiome has recently been reported to interact with environmental factors such as diet and exposure to environmental toxicants. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) induces a shift in the gut microbiome metabolic pathways, favoring a proinflammatory microenvironment. In addition, other studies have also correlated cancer incidence with exposure to PAHs. PAHs are known to induce organ carcinogenesis through activating a ligand-activated transcriptional factor termed the aryl hydrocarbon receptor (AhR), which metabolizes PAHs to highly reactive carcinogenic intermediates. However, the crosstalk between AhR and the microbiome in mediating carcinogenesis is poorly reviewed. This review aims to discuss the role of exposure to environmental pollutants and activation of AhR on microbiome-associated cancer progression and explore the underlying molecular mechanisms involved in cancer development

Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression

International audienceAbstract Diabetes mellitus (DM)-induced cardiac morbidities have been the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors including empagliflozin (EMPA), which have been approved for the treatment of DM, have gained attention for their cardioprotective effect. The mechanism by which SGLT-2 inhibitors exert their cardioprotective effect remains unclear. Recent studies have suggested that EMPA exerts its cardioprotective effect by inhibiting the Na + /H + exchanger (NHE), a group of membrane proteins that regulate intracellular pH and cell volume. Increased activity and expression of NHE isoform 1 (NHE1), the predominant isoform expressed in the heart, leads to cardiac hypertrophy. p90 ribosomal s6 kinase (p90 RSK) has been demonstrated to stimulate NHE1 activity. In our study, H9c2 cardiomyoblasts were treated with angiotensin II (ANG) to activate NHE1 and generate a hypertrophic model. We aimed to understand whether EMPA reverses the ANG-induced hypertrophic response and to elucidate the molecular pathway contributing to the cardioprotective effect of EMPA. Our study demonstrated that ANG-induced hypertrophy of H9c2 cardiomyoblasts is accompanied with increased SGLT-1 and NHE1 protein expression, an effect which is prevented in the presence of EMPA. EMPA reduces ANG-induced hypertrophy through the inhibition of SGLT-1 and NHE1 expression

Int J Mol Sci

Abnormality in glucose homeostasis due to hyperglycemia or insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM). These metabolic abnormalities in T2DM lead to cellular dysfunction and the development of diabetic cardiomyopathy leading to heart failure. New antihyperglycemic agents including glucagon-like peptide-1 receptor agonists and the sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to attenuate endothelial dysfunction at the cellular level. In addition, they improved cardiovascular safety by exhibiting cardioprotective effects. The mechanism by which these drugs exert their cardioprotective effects is unknown, although recent studies have shown that cardiovascular homeostasis occurs through the interplay of the sodium-hydrogen exchangers (NHE), specifically NHE1 and NHE3, with SGLT2i. Another theoretical explanation for the cardioprotective effects of SGLT2i is through natriuresis by the kidney. This theory highlights the possible involvement of renal NHE transporters in the management of heart failure. This review outlines the possible mechanisms responsible for causing diabetic cardiomyopathy and discusses the interaction between NHE and SGLT2i in cardiovascular diseases

Unlocking the secrets: exploring the influence of the aryl hydrocarbon receptor and microbiome on cancer development

Gut microbiota regulates various aspects of human physiology by producing metabolites, metabolizing enzymes, and toxins. Many studies have linked microbiota with human health and altered microbiome configurations with the occurrence of several diseases, including cancer. Accumulating evidence suggests that the microbiome can influence the initiation and progression of several cancers. Moreover, some microbiotas of the gut and oral cavity have been reported to infect tumors, initiate metastasis, and promote the spread of cancer to distant organs, thereby influencing the clinical outcome of cancer patients. The gut microbiome has recently been reported to interact with environmental factors such as diet and exposure to environmental toxicants. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) induces a shift in the gut microbiome metabolic pathways, favoring a proinflammatory microenvironment. In addition, other studies have also correlated cancer incidence with exposure to PAHs. PAHs are known to induce organ carcinogenesis through activating a ligand-activated transcriptional factor termed the aryl hydrocarbon receptor (AhR), which metabolizes PAHs to highly reactive carcinogenic intermediates. However, the crosstalk between AhR and the microbiome in mediating carcinogenesis is poorly reviewed. This review aims to discuss the role of exposure to environmental pollutants and activation of AhR on microbiome-associated cancer progression and explore the underlying molecular mechanisms involved in cancer development. </p

Unlocking the secrets: exploring the influence of the aryl hydrocarbon receptor and microbiome on cancer development

Gut microbiota regulates various aspects of human physiology by producing metabolites, metabolizing enzymes, and toxins. Many studies have linked microbiota with human health and altered microbiome configurations with the occurrence of several diseases, including cancer. Accumulating evidence suggests that the microbiome can influence the initiation and progression of several cancers. Moreover, some microbiotas of the gut and oral cavity have been reported to infect tumors, initiate metastasis, and promote the spread of cancer to distant organs, thereby influencing the clinical outcome of cancer patients. The gut microbiome has recently been reported to interact with environmental factors such as diet and exposure to environmental toxicants. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) induces a shift in the gut microbiome metabolic pathways, favoring a proinflammatory microenvironment. In addition, other studies have also correlated cancer incidence with exposure to PAHs. PAHs are known to induce organ carcinogenesis through activating a ligand-activated transcriptional factor termed the aryl hydrocarbon receptor (AhR), which metabolizes PAHs to highly reactive carcinogenic intermediates. However, the crosstalk between AhR and the microbiome in mediating carcinogenesis is poorly reviewed. This review aims to discuss the role of exposure to environmental pollutants and activation of AhR on microbiome-associated cancer progression and explore the underlying molecular mechanisms involved in cancer development. </p