Chemical Engineering
Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions
The endoplasmic reticulum (ER) is a sub-cellular organelle that is responsible for the correct folding of proteins lipid biosynthesis calcium storage and various post-translational modifications. In the disturbance of ER functioning unfolded or misfolded proteins accumulate inside the ER lumen and initiate downstream signaling called unfolded protein response (UPR). The UPR signaling pathway is involved in lipolysis triacylglycerol synthesis lipogenesis the mevalonate pathway and low-density lipoprotein receptor recycling. ER stress also affects lipid metabolism by changing the levels of enzymes that are involved in the synthesis or modifications of lipids and causing lipotoxicity. Lipid metabolism and cardiac diseases are in close association as the deregulation of lipid metabolism leads to the development of various cardiovascular diseases (CVDs). Several studies have suggested that lipotoxicity is one of the important factors for cardiovascular disorders. In this review we will discuss how ER stress affects lipid metabolism and their interplay in the development of cardiovascular disorders. Further the current therapeutics available to target ER stress and lipid metabolism in various CVDs will be summarized.
Evaluation of Enhanced Cytotoxicity Effect of Repurposed Drug Simvastatin/Thymoquinone Combination against Breast Cancer Cell Line
Introduction: Repurposing of drugs for their anticancer potential is gaining a lot of importance in drug discovery. Aims: The present study aims to explore the potential of Simvastatin (SIM) a drug used in the treatment of high cholesterol and Thymoquinone (Nigella Sativa) (THY) for its anti-cancer activity on breast cancer cell lines. Thymoquinone is reported to have many potential medicinal properties exhibiting antioxidant antiinflammatory anti-cancer activities like inhibition of tissue growth and division. Methods: In this analysis we explored the inhibitory effects of the combination of Simvastatin ad Thymoquinone on two breast cancer cell lines viz MCF-7 and MDA-MB-231 cells. The combined effect of Simvastatin and Thymoquinone on Cell viability Colony formation Cell migration and orientation of more programmed cell death in vitro was studied. Cell cycle arrest in the G2/M phase was concomitant with the combined effect of SIM and THY persuading apoptosis and generating reactive oxygen species (ROS). Results: The cell cycle arrest with combined treatment was observed that only 1.8% and 1.1% cells gated in G2/M phase in MCF-7 & MDA-MB-231 cell. An increased apoptosis was observed when cells were treated in combination which was about 76.20% and 58.15% respectively for MCF-7 and MDA-MB-231 cells. Conclusion: It was concluded that the combined effect of simvastatin and thymoquinone stimulates apoptosis in breast cancer cells.
The Role of Gut Microbiota and Associated Compounds in Cardiovascular Health and its Therapeutic Implications
It is possible that gut bacteria may have a beneficial effect on cardiovascular health in humans. It may play a major role in the progression of a variety of cardiovascular diseases including Heart Failure (HF) Atherosclerosis Coronary Arterial Disease (CAD) Ischemic Heart Disease (IHD) and Others. Dysbiosis of the gut microbiota along with its direct and indirect impact on gut health may induce cardiovascular disorders. Although advanced studies have demonstrated the relationship of various metabolites to cardiovascular diseases (CVD) in animals translating their functional capacity to humans remains a significant area of research. This paper simplifies the demonstration of some compounds pathways and components like Trimethylamine N-oxide (TMAO) short-chain fatty acids (SCFAs) and butyrate production. It demonstrates how a change in eating habits causes TMAO and how the impact of different drugs on gut microbiota species and high consumption of Westernized food causes several heartrelated problems such as atherosclerosis and inflammation that can even become the cause of heart failure. Modulation of the gut microbiome on the other hand is a novel therapeutic measure because it can be easily altered through diet and other lifestyle changes. It could then be used to lower the risk of several CVDs.
MicroRNAs Targeting Critical Molecular Pathways in Diabetic Cardiomyopathy Emerging Valuable for Therapy
MicroRNAs have emerged as an important regulator of post-transcriptional gene expression studied extensively in many cancers fetal development and cardiovascular diseases. Their endogenous nature and easy manipulation have made them potential diagnostic and therapeutic molecules. Diseases with complex pathophysiology such as Diabetic Cardiomyopathy display symptoms at a late stage when the risk of heart failure has become very high. Therefore the utilization of microRNAs as a tool to study pathophysiology and device-sustainable treatments for DCM could be considered. The present review focuses on the mechanistic insights of diabetic cardiomyopathy and the potential role of microRNAs.
An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy
Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics the resistance against approved therapy remains an issue of concern. The resistance against the therapy is widely reported due to factors like clonal selection involvement of multiple developmental pathways and majorly defective mismatch repair (MMR) protein and functional O6- methylguanine DNA methyltransferase (MGMT) repair enzyme. Phytotherapy is one of the most effective alternatives to overcome resistance. It involves plant-based compounds divided into several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds comprised in these classes are extracted or processed from certain plant sources. They can target various proteins of molecular pathways associated with the progression and survival of GBM. Phytocompounds have also shown promise as immunomodulatory agents and are being explored for immune checkpoint inhibition. Therefore research and innovations are required to understand the mechanism of action of such phytocompounds against GBM to develop efficacious treatments for the same. This review gives insight into the potential of phytochemical-based therapeutic options for GBM treatment.
Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions
Multidrug-resistant ESKAPE pathogens are the leading cause of hospital-acquired infections across the globe posing challenges for clinicians. Random genetic mutations and constant exposure to antibiotics in healthcare settings result in strains resistant to commonly used antibiotics creating life-threatening conditions. If the magic of “antibiotics” is to be sustained a new class of antimicrobials against novel targets is urgently needed. This necessitates understanding and identifying novel biochemical pathways and bacterial virulence factors that can be targeted for therapeutic interventions. Keeping in view the unambiguous role of the kinome in bacterial survival and virulence this review provides a survey of effector bacterial kinases involved in evading host immune responses and drug resistance. The formation of biofilms is a critical feature associated with the pathogenesis and survival of ESKAPE organisms in the hostile host milieu. Hence kinases involved in the biofilm pathway are also elucidated for clinical relevance. In addition endeavors in the development of therapeutics against ESKAPE kinases are also summarized to provide direction to researchers pursuing the field.
Advances in Medical Biotechnology
Medicinal Plant-rich Diet: A Potential Therapeutic Role in Colorectal Cancer
Background: Colorectal cancer is estimated to become the leading cause of cancer death worldwide. Since most of the available therapies affect vital organs such as heart and liver herbal remedies as a substitute therapy have been reported in several evidence-based studies. Objective: Medicinal plants exhibit a diverse range of bioactive elements known for their medicinal properties such as anti-inflammatory anticancer antioxidant and antimicrobial effects. Phytochemicals present in medicinal plants significantly trigger different signaling pathways contributing to their therapeutic activities. This review covers a comprehensive summary of the therapeutic potential of an herbal diet in treating colorectal cancer and other ailments. Special attention will be given to exploring the interactions of medicinal plants with the microbiota and their associations with cancer pathways. Conclusion: A medicinal plant rich in bioactive compounds is a therapeutic option for colorectal cancer and potent cardioprotective and hepatoprotective agents. These bioactive compounds have demonstrated the ability to impede the growth of cancerous cells and trigger apoptosis. Our findings suggest that pomegranate garlic soybean olive green tea papaya and grapes are potential medicinal plants for combating cancer and related side effects. Bioactive compounds can modulate the gut microbiota's metabolism and short-chain fatty acid production shows cardioprotective effects and reduces the risk of colorectal cancer. Hence it can be stated that the interaction between a medicinal plant-rich diet and the gut microbiota plays a crucial role in preventing colorectal cancer and cardiac arrest.
Combined Administration of Metformin and Vitamin D: A Futuristic Approach for Management of Hyperglycemia
Diabetes is a series of metabolic disorders that can be categorized into three types depending on different aspects associated with age at onset intensity of insulin resistance and beta- cell dysfunction: Type 1 and 2 Diabetes and Gestational Diabetes Mellitus. Type 2 Diabetes Mellitus (T2DM) has recently been found to account for more than 85% of diabetic cases. The current review intends to raise awareness among clinicians/researchers that combining vitamin D3 with metformin may pave the way for better T2DM treatment and management. An extensive literature survey was performed to analyze vitamin D's role in regulating insulin secretion their action on the target cells and thus maintaining the normal glucose level. On the other side the anti-hyperglycemic effect of metformin as well as its detailed mechanism of action was also studied. Interestingly both compounds are known to exhibit the antioxidant effect too. Literature supporting the correlation between diabetic phenotypes and deficiency of vitamin D was also explored further. To thoroughly understand the common/overlapping pathways responsible for the antidiabetic as well as antioxidant nature of metformin and vitamin D3 we compared their antihyperglycemic and antioxidant activities. With this background we are proposing the hypothesis that it would be of great interest if these two compounds could work in synergy to better manage the condition of T2DM and associated disorders.
Salivary Biomarkers for Oral Cancer Detection: Insights from Human DNA and RNA Analysis
Oral cancer is a significant global health concern with a high mortality rate mainly due to late-stage diagnosis. Early detection plays a critical role in improving patient outcomes highlighting the need for non-invasive and accessible screening methods. Salivary biomarkers have emerged as a promising avenue for oral cancer detection leveraging advancements in human DNA and RNA analysis. Several DNA-based biomarkers such as genetic mutations chromosomal aberrations and epigenetic alterations have shown promise in detecting oral cancer at various stages. Likewise RNA-based biomarkers including microRNAs long non-coding RNAs and messenger RNAs have demonstrated potential for diagnosing oral cancer and predicting treatment outcomes. The integration of high-throughput sequencing technologies such as next-generation sequencing and transcriptomic profiling has enabled the identification of novel biomarkers and provided deeper insights into the molecular mechanisms underlying oral cancer development and progression. Despite the promising results challenges remain in standardizing sample collection establishing robust biomarker panels and validating their clinical utility. Nevertheless salivary biomarkers hold great promise as a non-invasive cost-effective and accessible approach for oral cancer detection ultimately leading to improved patient outcomes through early diagnosis and intervention. The analysis of genetic material obtained from saliva offers several advantages including ease of collection non-invasiveness and the potential for repeated sampling. Furthermore saliva reflects the physiological and pathological status of the oral cavity making it an ideal source for biomarker discovery and validation. This article presents a comprehensive review of the current research on salivary biomarkers for oral cancer detection focusing on insights gained from human DNA and RNA analysis.
Genetic Underpinnings of Pulmonary Fibrosis: An Overview
Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder in which genetic and environmental factors are involved in disease onset. Although by definition the disease is considered idiopathic in nature evidence-based studies have indicated familial cases of pulmonary fibrosis in which genetic factors contribute to IPF pathogenesis. Methods: Both common as well as rare genetic variants are associated with sporadic as well as familial forms of IPF. Although clinical inferences of the genetic association have still not been explored properly observation-based studies have found a genotypic influence on disease development and outcome. Results: Based on genetic studies individuals with a risk of IPF can be easily identified and can be classified more precisely. Identification of genetic variants also helps to develop more effective therapeutic approaches. Conclusion: Further comprehensive research is needed to get a blueprint of IPF pathogenesis. The rapidly evolving field of genetic engineering and molecular biology along with the bioinformatics approach will possibly explore a new horizon very soon to achieve this goal.
Efficacy of Dyslipidemia Control by Combination Therapy with Rosuvastatin 10 Mg and Ezetimibe 10 Mg Compared with Rosuvastatin 20 Mg Monotherapy in Patients with Chronic Coronary Syndromes: A Randomized, Single-blind Controlled Trial
Background: Studies have shown the combination treatment effectiveness of using rosuvastatin and ezetimibe in patients with chronic coronary artery disease. Our study aim to evaluate the effectiveness of dyslipidemia treatment with the combination of rosuvastatin and ezetimibe 10mg in patients with chronic coronary artery disease compared with 20 mg rosuvastatin. Objectives: To evaluate the effectiveness of dyslipidemia treatment with the target of LDL-c < 1.4 mmol/L between combination therapy with rosuvastatin 10 mg and ezetimibe 10 mg in patients with chronic coronary artery disease compared with monotherapy increasing the dose of rosuvastatin 20 mg in Vietnam. Methods: A randomized controlled clinical trial single-blind parallel-group with a 1:1 randomized ratio in 103 outpatients with chronic coronary syndromes treated with rosuvastatin 10mg daily. Group A received the combination therapy with rosuvastatin 10 mg plus ezetimibe 10 mg daily and group B received rosuvastatin 20 mg daily. The primary outcome was to assess the efficacy of low-density lipoprotein - cholesterol (LDL-c) control between rosuvastatin 10 mg plus ezetimibe 10 mg versus rosuvastatin 20 mg after 4 weeks and 8 weeks. Results: After 8 weeks of intervention the proportion of archived treatment target patients with LDL-c < 1.4 mmol/L in groups A and B was 69.2% and 44.2% respectively (Risk ratio (RR) = 1.57 p < 0.01) 50% LDL reduction was 27.9% and 55.8% respectively (RR = 2.00 p < 0.01) and archived both targets were 51.9% and 25.6% (RR = 2.03 p < 0.01). Conclusion: Group A's LDL-c reduction effect and target achievement proportion (Rosuvastatin 10mg + Ezetimibe 10 mg) were significantly higher than Group B's (Rosuvastatin 20 mg). Both medication therapies were safe in patients and the increased dose of monotherapy showed more side effects than the combination therapy.
Sodium Butyrate, a Gut Microbiota Derived Metabolite, in Type 2 Diabetes Mellitus and Cardiovascular Disease: A Review
Type 2 diabetes is characterized by elevated blood glucose levels leading to an increased risk of cardiovascular diseases. Sodium butyrate the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation has shown promising effects on metabolic diseases including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory anti-oxidative and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes including atherosclerosis (AS) heart failure (HF) hypertension and angiogenesis. Moreover we explore the pathophysiology of cardiovascular disease in type 2 diabetes focusing on hyperglycemia oxidative stress inflammation and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.
Recent Advances in Organocatalytic Synthesis and Catalytic Activity of Substituted Pyrrolidines
The emergence of enantioselective organocatalysis as a potent synthetic chemistry strategy that supports metal-catalyzed transformations has resulted in the creation of novel procedures for the synthesis of various chiral molecules. Organocatalysis is a desirable method for creating complex molecular structures due to its many benefits including its ease of use wide availability of catalysts and low toxicity. Chemists are actively exploring synthetic methodologies and looking into the applications of pyrrolidine-based organocatalysts. The application of organocatalysts spans a wide range of reaction types highlighting their ability to participate in a variety of catalytic processes. The current study offers a succinct summary of the principal strategic methods for producing pyrrolidine-based organocatalysts and demonstrating their usefulness in organic transformations.
Laser Synthesis of Catalytically Active Materials for Organic Synthesis and Sensor Technology
Introduction: The catalytic activity of metallic nanomaterials depends on their surface morphology. A widely known method is the laser synthesis of metal nanostructures by depositing on dielectric surfaces from aqueous solutions containing metal complexes. The article analyzes the factors that favor the production of conductive catalytic and sensory-active deposits by laser method. It is shown that the two main factors is the presence of a large number of charged defects on heterophase surfaces and the structure of metal-containing complexes in solution. This is typical for mono- and bimetallic alloys the components of which interact with the laser beams according to the autocatalytic type. Using the example of laser deposition from solutions of Co Ni Fe Zn and Ag salts with homo- and heterophase dielectrics the sensory and catalytic properties of the deposits are compared by impedance spectroscopy and voltammetry. It has been shown that heterophase precipitation significantly enhances the catalysis response. Background: It is known that the highest catalytic activity exhibits nanostructured and highly porous materials with a large specific surface area and materials containing surface heterogeneity in the form of charged acid-base centers. Such materials are necessary for the creation of new catalysts for organic synthesis and for the creation of new sensor materials for enzyme-free microbiosensors. Active development of new methods for the synthesis of such materials is underway. But not all of them give the expected result. Methods: Laser synthesis methods have the best prospects including the method of laser-induced metal deposition. This is the laser synthesis of metal nanostructures by depositing dielectric surfaces from aqueous solutions containing metal complexes. Results: Ц#144;rticle analyzes the factors that favor the production of conductive catalytic and sensory-active deposits by laser method. It is shown that the two main factors are the presence of a large number of charged defects on heterophase surfaces and the structure of a metal-contained complex in solution. This is typical for mono- and bimetallic alloys the components of which interact with the laser beam according to the autocatalytic type. Using the example of laser deposition from solutions of Co Ni Fe Zn and Ag salts with homo- and heterophase dielectrics the sensory and catalytic properties of the deposits are compared by impedance spectroscopy and voltammetry. Conclusion: It has been shown that heterophase precipitation significantly enhances the catalysis response. It is shown that the laser deposition reaction has an autocatalytic mechanism in a dynamic mode. The results of autocatalysis can be used in a stationary mode to create a microbiosensor for glucose as well as to create a technology for laser refining rare metals and hydrogen energy in a dynamic mode.
Synthesis and Anti TB Screening of α-Acyloxy Carboxamides via Passerini MCRs Prompted by GaCl3 and PEG-400 Media
Aims: The Isocyanides based Multi-component reactions (IMCRs) and Passerini reactions were performed by using GaCl3 and PEG-400 media to generate a library of new scaffolds. Background: The Isocyanides Multi-component reactions (IMCRs) have proven their importance due to their major advantages in synthetic and medicinal areas. Among various IMCRs Passerini stands for their pertinency in the novel adducts articulation and generates an amide functionality which shows unbeatable efficiency towards the generation of lead scaffolds. In the research fields PEG is acting as a versatile greener solvent due to its beneficial economic advantages. In general chiral-based separation is always a headache for the chemist and researchers tend to generate routes with major products such as single isomers. Most MCRs studied with metal-based synthesis and rather use Au or Pt-based catalyst Gallium that has been widely explored in chiral Lewis acid catalysis organo-catalysis or cooperative catalysis to generate a library of compounds with high stereoselectivity with mild reaction conditions. Objective: To find diverse scaffolds in the field of organic chemistry using easily accessible metal catalysts. Methods: In this article Enantiomerically pure 2-(((1H-benzo[d][123]triazol-1-yl)methyl)amino)-2-oxo-1-substitutedphenylethyl pyrazine-2-carboxylate (4a-4j) produced through a three-component passerine coupling reaction under GaCl3 as a Lewis acid-promoted conditions with diastereoseletivity ranging from moderate to good. Results: The designed approach exhibited an in situ single-step-economical path to enantiomerically pure α-acyloxy carboxamides with pyrazine and 1H-benzo[d][123]triazole fragments employing the greener way of media through “PEG-400”. In an anti-TB screening against H37Rv the withdrawing groups showed excellent activity compared to the donating groups. Conclusion: It was expected that the Lewis acid-PEG pairs could serve as the best catalytic transformations in eco-friendly ways and enrich the pure enantiomer of the adduct. On the medicinal side the isolated library of compounds was screened for their biological activity against “Mycobacterium Tuberculosis H37Rv” and 4f featuring “4-F” as a substituent was found to be most active (MIC: 12.5 μg/mL).
Green Synthesis of Au-Ni Bimetallic Nanoparticles using Aqueous Extract of Coccinia grandis (L.) Voigt and their Catalytic Activity in Oxidation of Alcohols
Background: In recent years bimetallic nanoparticles have gained remarkable attention due to their excellent physical and chemical properties. Especially bimetallic nanoparticles are found to be highly efficient as catalysts in many important organic transformations. Objective: The objective of the present work involves green synthesis of Au-Ni bimetallic nanoparticles using plant extract as the bio-reductant and to evaluate their catalytic efficiency in oxidation of alcohols. Methods: The experiment involves a simple and eco-friendly protocol for synthesis of Au-Ni bimetallic as well as their corresponding monometallic nanoparticles that involves the use of aqueous fruit seed extract of Coccinia grandis(L.) Voigt as the bio-reductant and tannic acid as the bio-stabilizer. The synthesized nanoparticles were characterized by using XRD TEM FTIR TGA etc. and their catalytic activity was evaluated for oxidation of alcohols. Results: The synthesized bimetallic nanoparticles have shown excellent catalytic activity towards aqueous phase oxidation of alcohols to aldehydes under ambient reaction conditions. Furthermore the results have revealed better effective performance of the bimetallic nanoparticles over the corresponding monometallic nanoparticles of gold and nickel establishing the synergic influence of the two metals. Another attractive feature of this work is that the Au-Ni bimetallic nanoparticles could be recycled and reused up to four catalytic cycles without any significant decline in product yield. Conclusion: The green synthesized bimetallic Au-Ni nanoparticles have shown excellent catalytic activity toward the oxidation of alcohols in aqueous media under ambient reaction conditions. In addition the nanoparticles are found to be successfully recyclable upto four catalytic cycles.
A Comprehensive Insight on Pharmacological Properties of Cilnidipine: A Fourth-generation Calcium Channel Blocker
Preventing the development of cardiovascular problems is a key objective of antihypertensive drugs. Many of the non-pressure related coronary risk factors for hypertension are thought to be connected to an increase in sympathetic activity. The sympathetic systems have N-type calcium channels at the nerve terminals that control neurotransmitter release. Cilnidipine is a unique fourth-generation calcium channel blocker with blocking action on both L-/N- type calcium channels. Several L-type calcium channel blockers (Nilvadipine amlodipine azelnidipine nifedipine etc.) have been used to treat hypertensive patients. Cilnidipine is a novel drug that exerts a hypotensive effect through vasodilation action via blocking L-type calcium channels and potent antisympathetic activity via blocking N-type calcium channels. Inhibiting N-type calcium channels might be a new approach to treating cardiovascular disorders. Therefore it is expected that cilnidipine may respond well to complicated hypertension. The present review aims to describe the management mechanism of hypertension and other pharmacological and physicochemical properties of cilnidipine. Cilnidipine has various other beneficial effects such as lipid-lowering effect reduced white coat effect improves insulin sensitivity in essential hypertensive patients ameliorates osteoporosis in ovariectomized hypertensive rats reduced arterial stiffness reduced the risk of pedal edema antinociceptive effects neuroprotective and renal protective effect probably through inhibition of N-type calcium channels. Cilnidipine distinguishes itself from other calcium channel blockers due to its wide range of beneficial pharmacological effects. In conclusion cilnidipine may be more advantageous than other dihydropyridines such as nisoldipine amlodipine azelnidipine and other antihypertensive drugs.
L-Tartaric Acid Inhibits Diminazene-induced Vasorelaxation in Isolated Rat Aorta
Aims: The study investigated the effect of L-tartaric acid on diminazene-indiuced vasorelaxation. Background: Diminazene is known to induce vasorelaxation through the stimulation of angiotensin- converting enzyme (ACE-2). Objective: This work was designed to study the effect of L-tartaric acid on diminazene-induced vasorelaxation using an ex vivo approach. Materials and Methods: In the current investigation the inhibitory effect of L-tartaric acid on diminazene-induced relaxation. Results: The results confirmed that L-tartaric acid was able to inhibit in a dose-dependent manner diminazene-induced vasorelaxation. Conclusion: This investigation provides important experimental evidence of the efficacy of Ltartaric acid in inhibiting diminazene-induced vasorelaxation.