Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.

BACKGROUND: Antibiotic-resistant microorganisms (ARMS) are the leading cause of socio-economic loss in the world, with historical evidence linking them to increased mortality and morbidity. METHODOLOGY: In this systematic review, we highlight a new treatment approach for antibiotic-resistant infections using 'Extracellular vesicle (EVs)-based therapy,' also known as cell- and drug-free therapy. Here, we categorize and summarize studies on EVs derived from various human sources, such as tissues, bodily fluids, or their condition media, emphasizing their anti-infective properties in the treatment of various infections. In addition, we contend that human adipose tissue (HAT) is a superior source of antimicrobial EVs (aEVs) and investigate the distinct antimicrobial properties of aEVs derived from a stromal vascular fraction (SVF) of human adipose tissue. In light of this, we described the limited literature and research gaps that are essential for using SVF-aEVs as personalized precision medicine. RESULT AND DISCUSSION: The notion behind adipose-derived SVF-EVs is supported by extensive literature searches that demonstrate growing trends in EV-based medical treatments as well as the larger therapeutic potential of HAT because of its extensive history of usage in regenerative medicine. CONCLUSION: Additionally, the underlying science that explains how the inflammatory process aids in the clearance of infections and the restoration of homeostasis after the host immune system successfully defends against foreign pathogens, as well as the fact that adipose-derived SVF is a noninvasive, cost-effective source of a variety of parent immune cells that produces a good yield of EVs with the same genetic make-up as their parent cells, make this concept worthwhile. This research may thereby increase survival rates and survival quality in cases of resistant infections. Vocabulary: Drug- and cell-free therapy = Nano molecules (extracellular vesicles) used as a therapeutic source without the need for chemical drugs or cell transplantation. Anti-infection EVs (aEVs) = Nature's own anti-infection powered EVs (unmodified).

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used pharmaceuticals and tons of kilos are produced annually. Ibuprofen is one of the core medicines of non-steroidal anti-inflammatory drug and is primarily used for reduced pain, fever and tissue inflammation. It is also available for the treatment of osteoarthritis, rheumatoid arthritis, tendonitis, etc. It is still one of the most prescribed non-steroidal anti-inflammatory drugs in contemporary times. Although ibuprofen is a drug that has been used for years, it is also known to have various serious toxic effects. OBJECTIVE: In this review, we aimed to clarify toxic and genotoxic effects of Ibuprofen by analyzing major journal indexes. METHODS: The search was concentrated on the Web of Science, PubMed, Science Direct, Scopus, EBSCO Host, and Google Scholar databases, including the keyword combinations "genotoxicity", "toxicity", "Ibuprofen". RESULTS: In the search procedure, a total number of 11738 studies about the topic were reviewed. Consequently, 42 studies were classified as appropriate according to the inclusion criteria and were therefore included in the review. The results presented and discussed in this review indicate that Ibuprofen might represent a toxic, genotoxic and teratogenic risk for non-target, freshwater invertebrates, vertebrates and toxic for human especially in overdose or misuse situation. CONCLUSION: Ibuprofen generally was found to be toxic, mutagenic, teratogenic and genotoxic agent in various organisms. In human cases mostly overdose or misuse was found to be toxic. However acute toxicity was also reported in some human clinical studies. More detailed genotoxicity, teratogenicity and especially carcinogenic potential should be investigated to reach full decision of its safety.

INTRODUCTION: Postnatal cardiomyocytes respond to stress signals by hypertrophic growth and fetal gene reprogramming, which involves epigenetic remodeling mediated by histone methyltransferase polycomb repressive complex 2 (PRC2) and histone deacetylases (HDACs). However, it remains unclear to what extent these histone modifiers contribute to the development of cardiomyocyte hypertrophy. METHODS: Neonatal rat ventricular myocytes (NRVMs) were stimulated by phenylephrine (PE; 50μM) to induce hypertrophy in the presence or absence of the PRC2 inhibitor GSK126 or the HDACs inhibitor Trichostatin A (TSA). Histone methylation and acetylation were measured by Western blot. Cell size was determined by wheat germ agglutinin (WGA) staining. Cardiac hypertrophy markers were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: PE treatment induced the expression of cardiac hypertrophy markers, including natriuretic peptide A (Nppa), natriuretic peptide B (Nppb), and myosin heavy chain 7 (Myh7), in a time-dependent manner in NRVMs. Histone modifications, including H3K27me3, H3K9ac, and H3K27ac, were dynamically altered after PE treatment. Treatment with TSA and GSK126 dose-dependently repressed histone acetylation and methylation, respectively. While TSA reversed the PE-induced cell size enlargement in a wide range of concentrations, cardiomyocyte hypertrophy was only inhibited by GSK126 at a higher dose (1μM). Consistently, TSA dose-dependently suppressed the induction of Nppa, Nppb, and Myh7/Myh6 ratio, while these indexes were only inhibited by GSK126 at 1μM. However, TSA, but not GSK126, caused pro-hypertrophic expression of pathological genes at the basal level. CONCLUSION: Our data demonstrate diversified effects of TSA and GSK126 on PE-induced cardiomyocyte hypertrophy, and shed light on epigenetic reprogramming in the pathogenesis of cardiac hypertrophy.

BACKGROUND: Worldwide, millions of people are affected by liver disorders and issues, and the successful treatment of patients seems challenging even after many treatment strategies. Presently, doctors are left with treatments like liver transplantation and resection. Researchers found it challenging to target the liver due to various drawbacks such as opsonization, mechanical entrapment, and RES uptake. METHODS: Literature (from the past ten years) on different research data on the treatment of liver diseases and study reports on the development of various nanocarriers targeting the liver have been collected using multiple search engines such as ScienceDirect, j-gate, google scholar, PubMed, sci-hub, etc. and data have been compiled accordingly. RESULTS: The basics of liver anatomy and various liver cells and pathophysiology of liver diseases, and liver targeting have been mentioned better to understand the further treatment of various liver disorders. Various Liver diseases such as hepatitis B, liver fibrosis, hepatocellular carcinoma, acute liver failure, and liver cirrhosis have been detailed in multiple research studies related to their treatment. Various strategies for active and passive liver targeting have also been overviewed. Several advanced reported nanocarriers (liposomes, polymeric micelles, nanoparticles, micro and nanoemulsions, and phytosomes) are mentioned and their potential in treating liver disorders has been summarized by compiling research reports related to these nanocarriers. CONCLUSION: The fabrication of nanomedicine incorporating nanocarriers and biomaterials for treating liver diseases is a big challenge. Understanding various aspects of liver anatomy and liver cells is the prime requirement while designing successful liver-targeted nano/microcarriers. Also, the choice of advanced or modified polymeric material in liver targeting is very crucial for their specific liver cell targeting, for their biocompatibility and biodegradability point of view.

Non-alcoholic fatty liver disease [NAFLD] is a common metabolic disorder associated with obesity, diabetes mellitus, dyslipidemia and cardiovascular disease. A "multiple hit" model has been a widely accepted explanation for the disease's complicated pathogenesis. Despite advances in our knowledge of the processes underlying NAFLD, there is no conventional pharmaceutical therapy. The only currently approved option is to make lifestyle modifications, such as dietary and physical activity changes. The use of medicinal plants in the treatment of NAFLD has gained interest. Thus, we review the current knowledge about these agents based on clinical and preclinical studies. Moreover, the association between NAFLD and colorectal cancer [CRC], one of the most common and lethal malignancies, has recently emerged as a new study area. We overview the shared dysregulated pathways and the potential therapeutic effect of herbal medicines for CRC prevention in patients with NAFLD.

Humanity has been battling with tuberculosis (TB) for a long period, and despite the availability of drugs well-known to act against the deadly microbe, the menace is still very far from reaching its end. Moreover, problems related to TB chemotherapy, such as lengthy treatment periods leading to poor patient compliance, increasing drug resistance, and association with another deadlier disease HIV-AIDS, make the situation alarming, thereby pressing the need for the discovery of new potent drugs urgently. Therefore, a drug target that is essential for survival and exclusive to M. tuberculosis presents a promising platform to explore novel molecules against the microorganism for better pathogen clearance with minimal toxicity. The shikimate pathway that leads to the synthesis of essential aromatic amino acids is one such attractive target. Shikimate kinase, the fifth enzyme of this pathway, converts shikimate to shikimate-3-phosphate by using ATP as a co-substrate. Targeting shikimate kinase could be an effective strategy in light of its essentiality and absence of any homologue in mammals. This review discusses different strategies adopted for discovering novel compounds or scaffolds targeting M. tuberculosis shikimate kinase (MtSK) in vitro. The application of substrate analogues, their structure, and ligand-based approach for screening a library of anti-mycobacterial compounds, marine-derived molecules, and commercially available libraries have yielded promising MtSK inhibitors exhibiting micro-molar activities. To develop these leads into future drugs with minimum off-target effects on the host microenvironment, the molecules need to be structurally optimized for improved activities against enzymes and whole-cell organisms.

Bone morphogenetic proteins are a center of serious concern and are known to execute various cancer-related issues. The BMP signaling cascades have become more unpredictable as a result of their pleiotropic and risky characteristics, particularly when it comes to cancer responses. This perspective discusses the current therapeutic implications, emphasizes different cellular aspects that impact the failures of the current drug treatments, and speculates on future research avenues that include novel strategies like metabolomic studies and bio-mimetic peptide therapeutics to mitigate cancerous outcomes.

Stimulator of interferon genes (STING) plays a vital role in the human innate immune system. Aberrant expression of STING has been proven to be associated with several diseases, such as STING-associated vasculopathy with onset in infancy, Aicardi-Goutieres syndrome, and systemic lupus erythematosus. Therefore, inhibition of the STING signaling pathway can also be expected to provide effective therapeutic strategies for treating specific inflammatory and autoimmune diseases. However, the development of STING inhibitors is still in its infancy. There is still a need for additional efforts toward the discovery of new skeletons and more potent lead compounds for STING inhibition to meet clinical demand. In this review, we provide a summary of STING inhibitors, classified by different structural skeletons, reported in patents published from 2019 to July 2022. In addition, we also focus on the STING inhibitors, representative structures, biological activity, and mechanisms of action.

Brain-related disorders are one of the world's most important and complex health problems today. These brain-related disorders are responsible for a massive number of morbidities and death all around the world. However, researchers have devoted a large amount of time to investigating these diseases and found positive results; nevertheless, there are currently quite a few medications available to treat them. Emodin (EM), a polyphenol compound, has many health benefits. It is a biologically active monomer derived from rhubarb root that exhibits anti-inflammation, anti-oxidation, anticancer, and neuroprotective properties. A series of preclinical trials have shown EM to have protective benefits against many brain-related diseases. This review has evaluated the potential of EM as a pharmacological agent for the treatment and management of various brain-related disorders based on the findings of multiple pre-clinical studies and taking into account the compound's therapeutic properties.

BACKGROUND: Cancer is a life-threatening disease worldwide, but proper treatment has not yet been developed. Many therapies are available to treat cancer disorders, like chemotherapy, surgery, hormone therapy, and immunotherapy. Chemotherapy often relies on a combination of harmful, highly toxic platinum-based compounds. Also, there are chances of poor distribution of chemotherapeutic agents and cytotoxic to most cells which leads to damage to other healthy cells, also, there are chances of resistance. OBJECTIVE: The main objective of this study is the development of mesoporous silica nanoparticles. Mesoporous silica nanoparticles are recognized as carriers with high drug loading capacity and significant functionalized surface area for targeted drug delivery. Mesoporous silica nanoparticles have shape, particle size, pore volume, higher surface area, and the possibility of surface modification. Hence results in thermally and chemically stable nanomaterials. For targeted drug delivery, MSN is conjugated with a variety of ligands, including monoclonal antibodies, hyaluronic acid, transferrin, folic acid, etc., that have a particular affinity for the receptors that are overexpressed on the surface of malignant cells, so using this nanocarrier reducing the dose related toxicity of normal cell. METHODS: This review focuses on different methods for synthesizing mesoporous silica nanoparticles. Sol-gel method and modified stobber method were used for the synthesis of this nanoparticle. RESULTS: Successfully synthesized mesoporous silica nanoparticle with particle size around 50-200 nm and drug loading efficiency was found to be around 71 %. CONCLUSION: Mesoporous silica nanoparticles are great carriers for intracellular and targeted drug delivery systems.

INTRODUCTION: Glioblastoma multiforme (GBM) has a poor prognosis, with current treatments providing no advantage in terms of survival. Certain new immunotherapy methods, such as peptide vaccines, have been used in clinical trials. In this meta-analysis, the effectiveness of peptide vaccinations on the survival rate of GBM patients was studied. METHOD: A comprehensive search was carried out using three electronic databases: PubMed, Scopus, and ISI. The purpose of this research was to assess overall survival (OS). The pooled overall one-year and two-year survival rates in GBM with peptide vaccination were calculated using the general inverse variance technique as random effects hazard ratios (HRs). In the study, subgroups of countries were compared with each other. Japan had the highest one-year survival rate, and the US had the highest two-year survival rate. RESULT: With 95% confidence intervals (CIs), the one-year OS rate in GBM patients treated with peptide vaccination increased significantly, but the two-year survival rate did not increase. As a result, while additional research is needed, it cannot be concluded that it is an effective therapy for GBM. CONCLUSION: Our study found that while peptide vaccination treatment did not increase second-year survival, it improved first-year survival. More research needs to be done to find effective vaccine-based treatments for GBM that can help patients survive longer.

BACKGROUND: One of the major indications for digoxin use is the treatment of heart failure [HF]. Although clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction [HFrEF] patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction [HFpEF] is not very clear. OBJECTIVES: The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF. METHODS: PubMed, Embase, Scopus and Web of Science [ISI] electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF". RESULTS: Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality [HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %], all-cause hospitalization [HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %], HF-hospitalization [HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %], and all-cause mortality or HF-hospitalization [HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %]. In subgroup meta-analyses based on ejection fraction [EF] , treatment with digoxin did not significantly alter these outcomes in each subset of patients. CONCLUSION: The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including "all-cause mortality", "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".

The objective of this paper is to look at how natural medicines can improve cognition and memory when used with sildenafil, a popular erectile dysfunction medicine that also has nootropic properties. Newer treatment strategies to treat the early stages of these diseases need to be developed. Multiple factors lead to complex pathophysiological conditions, which are responsible for various long-term complications. In this review a combination of treatments targeting these pathologies are discussed. These combinations may help manage early and later phases of cognitive impairments. The purpose of this article is to discuss a link between these pathologies and a combinational approach with the objective of considering newer therapeutic strategies in the treatment of cognitive impairments. The natural drugs, and their ingredients play a major role in the management of disease progression. Additionally, their combination with sildenafil allows for more efficacy and better response. Studies showing effectiveness of natural drugs and sildenafil are mentioned and how the combinations could be beneficial for treatment of cognitive impairments and amnesia are summarised. Furthermore, preclinical and clinical trials are required to explore the medicative potential of these drug combinations.

BACKGROUND: Epilepsy is a neurological disease affected by an imbalance of inhibitory and excitatory signaling in the brain. INTRODUCTION: In this disease, the targets are active in pathophysiology and thus can be used as a focus for pharmacological treatment. METHODS: Several studies demonstrated the antiepileptic effect of drugs acting on the following targets: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, voltage-gated calcium channel (Cav), Gamma aminobutyric acid transporter type 1 (GAT1), voltage-gated sodium channels (Nav), voltage-gated potassium channel of the Q subfamily (KCNQ) and Gamma aminobutyric acid type A (GABAA) receiver. RESULTS: These studies highlight the importance of molecular docking. CONCLUSION: Quantitative Structure-Activity Relationship (QSAR) and computer aided drug design (CADD) in predicting of possible pharmacological activities of these targets.

Alzheimer's disease (AD) has become the fourth leading cause of death in the world. Due to its complex pathogenesis, there is still a lack of effective drug treatments. Studies have found that the metal dyshomeostasis is closely related to other pathogeneses of AD such as oxidative stress, β-amyloid protein deposits etc. Therefore, it becomes an important target to find the appropriate metal chelating agents to regulate the metal homeostasis. At the same time, because of the complex pathogenesis, single target drugs cannot achieve good effects. Therefore, current studies are mainly focused on exploring multi-target therapy for AD. In this work, the multi-target studies based on metal chelators and other targets with synergistic anti-AD activities were reviewed. The structural characteristics of different chelating agents were summarized and the structure-activity relationship was analyzed, which provided some valuable clues for the subsequent development of anti-AD multi-target drugs based on metal chelating agents.

Epidemiological evidence continues to accumulate on the effect of stress and depression with cancer initiation and progression. Depression has been introduced as an independent predictor of increased cancer mortality. Whereas early intervention for depression increases the survival rate. Even some evidence has given prognostic value for depression to predict cancer recurrence and mortality. This article presents current evidence on the correlations of molecular mechanisms of cancer and depression through; I. The evidence shows the role of pre-existing depression and anxiety in the development and progression of cancer. II. The Immune system performs a crucial role in stress, depression, and cancer. III. The role of stress and depression-induced inflammation. IV. The evidence has proposed that cancer may result in depression and the effect of depression on cancer outcome. In conclusion, the importance of preventive interventions to monitor patients' mental health during cancer treatment is very significant and should not be underestimated. In other words, the initial interventions can improve depressive symptoms and increase cancer survival. On the other hand, by identifying key biomarkers of depression, physicians can identify cancer patients who are at risk for depression or those who may not respond to routine treatments. Understanding how the cancer environment can cause pathophysiological phenomena helps develop new anti-depressant therapies and identify cancer patients that may be present during cancer. It can also help if the patients with cancer are prone to depression.

BACKGROUND: Flavonoids belong to the chemical class of polyphenols and are in the category of secondary metabolites imparting a wide protective effect against acute and chronic diseases. OBJECTIVE: The study aims to investigate and summarize the information of various flavonoids which were extracted, isolated from various sources, and possess different pharmacological properties by acting on multiple targets. METHODS: This comprehensive review summarizes the research information related to flavonoids and their pharmacological action targets from various sources like PubMed. google scholar and google websites. RESULT: Extracted information in the paper discusses various therapeutic effects of flavonoids isolated from medicinal plant sources which have the property to inhibit several enzymes which finally results in health benefits like anti-cancer, anti-bacterial, antioxidant, anti-allergic, and anti-viral effects. This study also showed the different solvents and methods involved in the extraction and characterization of the isolated phytochemical constituents. CONCLUSION: The findings showed the contribution of several flavonoids in the management and inhibition of various acute and chronic sicknesses by acting on different sites in the body. This study may lead to gaining the interest for more research on the bioactives of different medicinal plants for the discovery of new lead compounds or further improvement of the efficacy of the existing compound.

Bone diseases such as rheumatoid arthritis, Paget's disease, and osteoporosis cause mortality and mobility limits. Nanomedicine and nano delivery systems have been utilised to deliver active drug moiety to the precisely targeted site in a controlled manner, and it serves as a means of diagnostic tools. The utilisation of nanomedicine is expanding vigorously for assured targeting and efficient drug delivery. Nanotechnology offers various advantages, such as site-specific targeting, precise drug release kinetics, and improved bone mineral density. Recent medications available for osteoporosis aren't viable due to the adverse effects associated with them and low patient compliance. There is an urgent need to develop biocompatible and appropriate drug delivery nanocarriers such as nanoparticles, liposomes, hydrogels, dendrimers, micelles, mesoporous particles, etc. These carriers enhance drug delivery and therapeutic effectiveness in bone tissues. The use of nanotechnology is also associated with toxicity. This article presents the review of various reports on nanocarrier systems and biologics for the treatment of osteoporosis. It aims to provide researchers with a clue for inventing a new drug delivery system with site-specific targeting for the treatment of osteoporosis.

Protein acetylation is a reversible central mechanism to control gene expression and cell signaling events. Current evidence suggests that pharmacological inhibitors for protein deacetylation have already been used in various disease conditions. Accumulating reports showed that several compounds that enhance histone acetylation in cells are in both the preclinical and clinical development stages targeting non-communicable diseases, which include cancerous and non-cancerous especially cardiovascular complications. These compounds are, in general, enzyme inhibitors and target a family of enzymes- called histone deacetylases (HDACs). Since HDAC inhibitors have shown to be helpful in preclinical models of cardiac complications, further research on developing novel compounds with high efficacy and low toxicity may be essential for treating cardiovascular diseases. In this review, we have highlighted the roles of HDAC and its inhibitors in cardiac complications.