The BET protein family plays a crucial role in regulating the epigenetic landscape of the genome. Their role in regulating tumor-related gene expression and its impact on the survival of tumor cells is widely acknowledged. Among the BET family constituents, BRD4 is a significant protein. It is a bromodomain-containing protein located at the outer terminal that recognizes histones that have undergone acetylation. It is present in the promoter or enhancer region of the target gene and is responsible for initiating and sustaining the expression of genes associated with tumorigenesis. BRD4 expression is significantly elevated in various tumor types. Research has indicated that BRD4 plays a significant role in regulating various transcription factors and chromatin modification, as well as in repairing DNA damage and preserving telomere function, ultimately contributing to the survival of cancerous cells. The protein BRD4 has a significant impact on antitumor therapy, particularly in the management of lung cancer and hematological malignancies, and the promising potential of BRD4 inhibitors in the realm of cancer prevention and treatment is a topic of great interest. Therefore, BRD4 is considered a promising candidate for prophylaxis and therapy of neoplastic diseases. However, further research is required to fully comprehend the significance and indispensability of BRD4 in cancer and its potential as a therapeutic target.

There have been several neglected infectious pathogens that have reemerged in the last few decades, including the monkeypox virus, a virus from the orthopoxviral genus that causes monkeypox and is transmitted between animals and humans. The human monkeypox outbreak has spread to several different countries. Because of the outbreak's unusually high case count and lack of connections to endemic nations, there are concerns that the monkeypox transmission pattern may have changed. The current study aimed to provide recent advancements in the prevention and management of the monkeypox virus in humans. We have highlighted recent advancements in the prevention and management of the monkeypox virus in humans in this work. For the treatment and prevention of monkeypox, new medications and vaccinations are being used, and more study is needed to understand the epidemiology, biology, and ecology of the virus in endemic regions and stop future global outbreaks. Vaccines available in the market for the treatment of viruses are JYNEOS and ACAM2000. Some of the antiviral drugs, such as tecovirimat, brincidofovir, cidofovir, trifluridine, and vaccinia immune globulin, are used for the treatment of the monkeypox virus. Some of the vaccines, such as NIOCH-14, Cidofovir, CMX-001, and ST-246, are currently in clinical trials. We have, herein, covered features of monkeypox viral biology that are important for risk assessment and getting ready for an outbreak of the monkeypox virus, with a focus on recent advances in knowledge of the virus's host range, evolutionary potential, and potential targets for neutralization.

Leishmaniasis is one of the Neglected Tropical Diseases (NTDs), a zoonotic disease of vector-borne nature that is caused by a protozoan parasite Leishmania. This parasite is transmitted by the vector sandfly into the human via a bite. Visceral leishmaniasis (VL), also called kala-azar, is the most fatal among the types of leishmaniasis, with high mortality mostly spread in the East Africa and South Asia regions. WHO report stated that approximately 3.3 million disabilities occur every year due to the disease along with approximately 50,000 annual deaths. The real matter of concern is that there is no particular effective medicine/vaccine available against leishmaniasis to date except a few approved drugs and chemotherapy for the infected patient. The current selection of small compounds was constrained, and their growing drug resistance had been a major worry. Additionally, the serious side effects on humans of the available therapy or drugs have made it essential to discover efficient and low-cost methods to speed up the development of new drugs against leishmaniasis. Ideally, the vaccine could be a low risk and effective alternative for both CL and VL and elicit long-lasting immunity against the disease. There are a number of vaccine candidates at various stages of clinical development and preclinical stage. However, none has successfully passed all clinical trials. But, the successful development and approval of commercially available vaccines for dogs against canine leishmaniasis (CanL) provides evidence that it can be possible for humans in distant future. In the present article, the approaches used for the development of vaccines for leishmaniasis are discussed and the progress being made is briefly reviewed.

Statins, especially simvastatin promote bone formation by stimulating the activity of osteoblasts and suppressing osteoclast activity via the BMP-Smad signaling pathway. Statins present the liver first-pass metabolism. This study attempts to fabricate and evaluate simvastatin functionalized hydroxyapatite encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (HSIM-PLGA NPs) administered subcutaneously with sustained release properties for effective management of osteoporosis. Simvastatin functionalized hydroxyapatite (HSIM) was prepared by stirring and validated by docking studies, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Further, HSIM-loaded PLGA nanoparticles (HSIM-PLGA NPs) were developed via the solvent emulsification method. The nanoparticles were evaluated for zeta potential, particle size, entrapment efficiency, stability studies, and in vitro drug release studies. In vitro binding affinity of nanoparticles for hydroxyapatite was also measured. Bone morphology and its effect on bone mineral density were examined by using a glucocorticoid-induced osteoporosis rat model. The optimized nanoparticles were found to be amorphous and showed no drug-polymer interaction. The particle size of formulated nanoparticles varied from 196.8±2.27nm to 524.8±5.49 nm and the entrapment efficiency of nanoparticles varied from 41.9±3.44% to 70.8± 4.46%, respectively. The nanoparticles showed sustained release behaviour (75% in 24 hr) of the drug followed by non-fickian drug release. The nanoparticles exhibited high binding affinity to bone cell receptors, increasing bone mineral density. A significant difference in calcium and phosphorous levels was observed in disease and treatment rats. Porous bone and significant improvement in porosity were observed in osteoporotic rats and treated rats, respectively (P<0.05). Bone-targeting nanoparticles incorporating functionalized simvastatin can target bone. Thus, in order to distribute simvastatin subcutaneously for the treatment of osteoporosis, the developed nanoparticles may act as a promising approach.

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.

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. 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. 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. 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).

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.

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. 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. 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. 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.

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. 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. 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. Successfully synthesized mesoporous silica nanoparticle with particle size around 50-200 nm and drug loading efficiency was found to be around 71 %. Mesoporous silica nanoparticles are great carriers for intracellular and targeted drug delivery systems.

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.