The Role of Diazepam in Epigenetics: From the Molecular Level to Clinical Implications.

There is growing evidence linking epigenetic mutations to neurologic disorders such as epilepsy. The effect of the medications primarily used to treat neurologic disorders has recently been studied, including research on epilepsy and the epigenetic process. The impact of the widely used medication diazepam on epigenomics, microRNA levels, the ensuing genetic exposure and potential clinical effects was reviewed. The action of diazepam, particularly in altering the synthesis of enzyme 5' adenosine monophosphate activated protein kinase (AMPK) was found to affect many enzymes, which changes or modifies the epigenetics. Epigenetic enzymes such as histone acetyltransferases (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) are mainly activated by AMPKs, including the phosphorylate substrates, which often lead to their inhibition, although HAT1 activity may be improved. It has been reported that diazepam can reduce histone methyltransferase expression exposure, may increase class III histone deacetylases activity and may decrease the effect of DNA methyltransferases inhibitors. Diazepam has been found to contribute to mutations of the epigenome and genetic expression, and may protect against neurologic disorders, aging, dementia and several brain diseases. It has also been found that microRNA expression can be influenced by diazepam treatment and may have neurologic effects. Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear.

The Impact of COVID-19 Pandemic Infection in Patients Admitted to the Hospital for Reasons Other Than COVID-19 Infection.

COVID-19 or SARS CoV-2 is a worldwide public health emergency. The first case of COVID-19 was described in Wuhan, China in December, 2019 and within a short time the infection had spread quickly to the rest of China and then the world. The COVID-19 pandemic has had a huge impact on patients who do not have COVID-19 but other diseases like cancer, diabetes, and many more non-communicable diseases; their care is compromised because of the pandemic. COVID-19 also poses a work-related health risk for healthcare workers who are treating patients with COVID-19, and many have themselves become infected. Healthcare workers involved in diagnosing and treating patients with COVID-19 should be evaluated for stress, anxiety and depression.

Granulated colloidal silicon dioxide-based self-microemulsifying tablets, as a versatile approach in enhancement of solubility and therapeutic potential of anti-diabetic agent: formulation design and in vitro/in vivo evaluation.

The current research work was executed with an aim to explore and promote the potential of self-microemusifying drug delivery systems (SMEDDS) in the form of tablets, in order to enhance solubility and oral bioavailability of poorly aqueous soluble drug Repaglinide (RPG). RPG-loaded liquid SMEDDS were developed consisting Labrafil M 1944CS, Kolliphor EL and Propylene glycol, which were then characterized on various parameters. After characterization and optimization, liquid SMEDDS were converted into solid form by adsorbing on Aeroperl® 300 pharma and polyplasdoneTM XL. Further, selection of suitable excipients was done and mixed with prepared solidified SMEDDS powder followed by the preparation of self-microemulsifying tablets (SMET's) wet granulation-compression method. SMET's were subjected to differential scanning calorimetry (DSC) and particle X-ray diffraction (RXRD) studies, results of which indicated transformation of crystalline structure of RPG because of dispersion of RPG at molecular level in liquid SMEDDS. This was further assured by micrographs obtained from scanning electron microscope. SMET's shown more than 85% (30 min) of in vitro drug release in contrast to conventional marketed tablets (13.2%) and pure RPG drug (3.2%). Results of in vivo studies furnished that SMET's had shown marked decrease in the blood glucose level and prolonged duration of action (up to 8 h) in comparison with conventional marketed tablets and pure RPG drug. In conclusion, SMET's serves as a promising tool for successful oral delivery of poorly aqueous soluble drug(s) such as RPG.

Unlocking ß-cell restoration: The crucial role of PDX1 in diabetes therapy.

Diabetes has been a significant healthcare problem worldwide for a considerable period. The primary objective of diabetic treatment plans is to control the symptoms associated with the pathology. To effectively combat diabetes, it is crucial to comprehend the disease's etiology, essential factors, and the relevant processes involving ß-cells. The development of the pancreas, maturation, and maintenance of ß-cells, and their role in regular insulin function are all regulated by PDX1. Therefore, understanding the regulation of PDX1 and its interactions with signaling pathways involved in ß-cell differentiation and proliferation are crucial elements of alternative diabetes treatment strategies. The present review aims to explore the protective role of PDX1 in ß-cell proliferation through signaling pathways. The main keywords chosen for this review include "PDX1 for ß-cell mass," "ß-cell proliferation," "ß-cell restoration via PDX1," and "mechanism of PDX1 in ß-cells." A comprehensive literature search was conducted using various internet search engines, such as PubMed, Science Direct, and other publication databases. We summarize several approaches to generating ß-cells from alternative cell sources, employing PDX1 under various modified growth conditions and different transcriptional factors. Our analysis highlights the unique potential of PDX1 as a promising target in molecular and cell-based therapies for diabetes.

Unraveling the impact of miR-21 on apoptosis regulation in glioblastoma.

Glioblastoma is a prevalent form of carcinoma that exhibits a greater incidence rate across diverse demographics globally. Despite extensive global efforts, GBM continues to be a highly lethal disease that is characterized by a grim prognosis. There is a wealth of evidence suggesting that the pathophysiology of GBM is associated with the dysregulation of numerous cellular and molecular processes. The etiology of GBM may involve various cellular and molecular pathways, including EGFR, PDCD4, NF-κB, MAPK, matrix metalloproteinases, STAT, and Akt. MicroRNAs, short non-coding RNA molecules, regulate gene expression and mRNA translation after transcription but before translation to exert control over a wide range of biological functions. Extensive research has consistently demonstrated the upregulation of miRNA-21 in glioma, indicating its involvement in diverse biological pathways that facilitate tumor cell survival. By explaining the intricate interplay between miR-21 and the regulation of apoptosis in GBM, this review has the potential to significantly enhance our comprehension of the illness and provide potential targets for therapeutic intervention.

Galangin as an inflammatory response modulator: An updated overview and therapeutic potential.

Numerous chronic diseases, such as cancer, diabetes, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders, all have an inflammation-based etiology. In cellular and animal models of inflammation, flavonols were used to show potent anti-inflammatory activity. The flavonols enhanced the synthesis of the anti-inflammatory cytokines transforming growth factor and interleukin-10 (IL-10) and reduced the synthesis of the prostaglandins IL-6, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2), IL-1. Galangin (GAL), a natural flavonol, has a strong ability to control apoptosis and inflammation. GAL was discovered to suppress extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)p65 phosphorylation, which results in anti-inflammatory actions. Arthritis, inflammatory bronchitis, stroke, and cognitive dysfunction have all been treated with GAL. The current review aimed to demonstrate the anti-inflammatory properties of GAL and their protective effects in treating various chronic illnesses, including those of the heart, brain, skin, lungs, liver, and inflammatory bowel diseases.

Possible underlying influence of p38MAPK and NF-κB in the diminished anti-anxiety effect of diazepam in stressed mice.

The present study was designed to explore the possible nitriergic influence and role of p38MAPK and NF-κB in the diminished anti-anxiety effect of diazepam in stressed mice, using the elevated plus maze and light/dark box to assess anxiety. Immobilization stress for 6 h enhanced an anxiety-like behavior and increased plasma nitrite levels in mice. Diazepam (2 mg/kg, i.p.) produced an anti-anxiety effect in unstressed mice, but could not produce any change in anxiety levels of stressed mice. SB-203580 (2 mg/kg, i.p.), a specific inhibitor of p38MAPK, per se produced a significant antianxiety-like activity in stressed mice. Administration of a combination of SB-203580 (2 mg/kg, i.p.) and diazepam (2 mg/kg) in stressed mice produced a significantly higher antianxiety-like activity than that produced by SB-203580 alone. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of the activation of NF-κB, per se produced a significant antianxiety-like activity in stressed mice. Combination of PDTC and diazepam also served to produce a higher significant antianxiety-like activity in stressed mice than that produced by PDTC alone. Diazepam could not produce any change in plasma nitrite levels in both unstressed and stressed mice. Both SB-203580 (2 mg/kg, i.p.) and PDTC (100 mg/kg, i.p.) significantly decreased plasma nitrite levels in stressed mice. The observations indicate that the diminished anti-anxiety effect of diazepam in stressed mice may involve strong nitriergic influence and may further be p38MAPK- and NF-κB-dependent.

Current update on psyllium and alginate incorporate for interpenetrating polymer network (IPN) and their biomedical applications.

Natural polysaccharides and their designed structures are extremely valuable due to their intrinsic pharmacological properties and are also used as pharmaceutical aids. These naturally occurring polysaccharides (e.g., psyllium and alginate) are gaining popularity for their use in the preparation of interpenetrating polymer network (IPN) materials with improved swelling ability, biodegradability, stability, non-cytotoxic, biocompatibility, and cost-effectiveness. IPN is prepared sequentially or simultaneously by microwave irradiation, casting evaporation, emulsification cross-linking, miniemulsion/inverse miniemulsion technique, and radiation polymerization methods. In addition, the prepared IPNs have has been extensively characterized using various analytical and imaging techniques before sustainable deployment for multiple applications. Regardless of these multi-characteristic attributes, the current literature lacks a detailed overview of the biomedical aspects of psyllium, alginate, and their engineered IPN structures. Herein, we highlight the unique synthesis, structural, and biomedical considerations of psyllium, alginate, and engineered IPN structures. In this review, a wide range of biomedical applications, such as role as a drug carrier for sustain delivery, wound dressing, tissue engineering, and related miscellaneous application of psyllium, alginate, and their IPN structures described with appropriate examples. Further research will be carried out for the development of IPN using psyllium and alginate, which will be a smart and active carrier for drugs used in the treatment of life-threatening diseases due to their inherent pharmacological potential such as hypoglycemic, immunomodulatory, antineoplastic, and antimicrobial.

A contemporary biological pathway of islet amyloid polypeptide for the management of diabetic dementia.

Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.

Nano Era of Dentistry-An Update.

BACKGROUND: Management of the health of oral tissues is a prime requirement in dentistry. The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges. The limitations in dental materials, medications, instruments, procedures put off the accomplishment of this goal. Rationalization of science and technology has made possible to work out these limitations. Nanotechnology which is the outcome of this rationalization has become one of the most favored technologies in medical and dental application. The substantial contribution of nano dental materials is the identification of oral health related problems by better diagnosis and management of dental disorders by bionanomaterials. CONCLUSION: Application of nanodentistry holds promise for comprehensive dental care by utilizing nanomaterials and ultimately by nanorobots. This review discusses the rationale of nanodentistry, nanocarriers researched in treatment of different dental diseases, the latest innovations in nanomaterials in various disciplines of dentistry; patent literature and related marketed products. Advances in nanotechnology have placed plenty of hopes in terms of improving the oral health care of dental patients.

Formulation and Characterization of Nanomedicine (Solid Lipid Nanoparticle) Associate with the Extract of Pterospermum acerifolium for the Screening of Neurochemicals and Neuroendocrine Effects.

BACKGROUND: Nanotechnology has given the likelihood of conveying medications to particular cells utilizing nanoparticles. Nanosystems can convey the dynamic constituent at an adequate fixation amid the whole treatment time frame, guiding it to the fancied site of activity. Traditional medications do not meet these necessities. The fundamental motivation behind creating elective medication conveyance advancements is to expand effectiveness of medication conveyance and security during the time spent medication conveyance and give more accommodation to the patient. OBJECTIVES: Pterospermum acerifolium, basic plant in India, is viewed as carminative, stimulant, and emmenagogue. The improvement of control discharge conveyance systems could prompt huge preferences in the clinical employments of these medications to diminish the toxicities. The point of this study was to figure another conveyance framework for impacts of neurochemicals by the joining of concentrate of P. acerifolium into strong lipid nanoparticles (SLNs). METHODS: SLN formulations were prepared by Ethanolic extract, lipid layer was liquefied by warming at 5°C above liquefying purpose of the lipid. After that, SLNs were separated and dried. Shape and surface morphology of the SLNs were pictured by checking scanning electron microscopy. Particle size and size distribution were dictated by photon connection spectroscopy. RESULTS AND DISCUSSION: The change of molecule charge was contemplated by zeta potential estimations. Treatment with SLN with concentrate was found to altogether diminish the serum levels of adrenocorticotropic hormone (ACTH), corticosterone and-endorphin and in addition the cerebrum and serum level of norepinephrine. Moreover, SLN with concentrate could essentially turn around the constant anxiety by diminishing the cerebrum and serum levels of the monoamine neurotransmitters dopamine, 5-hydroxytryptamine. CONCLUSION: The outcomes got from this study recommended that the memory-improving impact of SLN with concentrate was interceded through directions of neurochemical and neuroendocrine frameworks.

Investigation of in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetics of paromomycin: Influence on oral bioavailability.

OBJECTIVE: The objective of this study is to investigate in vitro Caco2 permeability, metabolism and in vivo pharmacokinetic (PK) properties of paromomycin to develop an efficient dosage form with improved oral bioavailability. MATERIALS AND METHODS: For the purpose, Caco2 permeability assay, mouse microsomal stability assay and in vivo PKs in male BALB/c mice were performed. RESULTS: In Caco-2 permeability assay, paromomycin showed negligible permeability in the apical to basolateral (A-to-B) direction and vice versa (B-to-A). Marginal increase in permeability with the use of P-glycoprotein (P-gp) inhibitor, namely, verapamil suggesting paromomycin could be a P-gp substrate. Paromomycin was unstable in liver microsomes of mouse. Paromomycin showed good PK properties after intravenous dose in male BALB/c mice which included low plasma clearance, i.e., <10% of hepatic blood flow in mice, high volume of distribution (Vd), and half-life (T½) of 2.6 h. Following per oral dose, it exhibits low oral bioavailability (0.3%) with carboxymethyl cellulose formulation. Oral plasma exposure increased in mice by 10% and 15% after pretreatment with P-gp inhibitor verapamil and CYP inhibitor 1-Aminobenztriazole, respectively. CONCLUSION: Comparatively significant increase in oral plasma exposure of paromomycin was observed with an alternative oral formulation approach, use of P-gp and CYP inhibitors resulting in improved oral bioavailability up to 16%.

Formulation and statistical optimization of self-microemulsifying drug delivery system of eprosartan mesylate for improvement of oral bioavailability.

The present investigation is aimed to design a statistically optimized self-microemulsifying drug delivery system (SMEDDS) of eprosartan mesylate (EM). Preliminary screening was carried out to find a suitable combination of various excipients for the formulation. A 3(2) full factorial design was employed to determine the effect of various independent variables on dependent (response) variables. The independent variables studied in the present work were concentration of oil (X 1) and the ratio of S mix (X 2), whereas the dependent variables were emulsification time (s), globule size (nm), polydispersity index (pdi), and zeta potential (mV), and the multiple linear regression analysis (MLRA) was employed to understand the influence of independent variables on dependent variables. Furthermore, a numerical optimization technique using the desirability function was used to develop a new optimized formulation with desired values of dependent variables. The optimized SMEDDS formulation of eprosartan mesylate (EMF-O) by the above method exhibited emulsification time, 118.45 ± 1.64 s; globule size, 196.81 ± 1.29 nm; zeta potential, -9.34 ± 1.2 mV, and polydispersity index, 0.354 ± 0.02. For the in vitro dissolution study, the optimized formulation (EMF-O) and pure drug were separately entrapped in the dialysis bag, and the study indicated higher release of the drug from EMF-O. In vivo pharmacokinetic studies in Wistar rats using PK solver software revealed 2.1-fold increment in oral bioavailability of EM from EMF-O, when compared with plain suspension of pure drug.

Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology.

BACKGROUND: This study was undertaken with an aim to systematically design a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology (RSM) by employing 3(2) full factorial design. MATERIALS AND METHODS: Mucoadhesive buccal patches were prepared using different grades of hydroxypropyl methylcellulose (HPMC) (K4M and K100M) and polyvinylpyrrolidone-K30 by solvent casting method. The amount of the release retardant polymers - HPMC K4M (X1) and HPMC K100M (X2) was taken as an independent variable. The dependent variables were the burst release in 30 min (Y1), cumulative percentage release of drug after 8 h (Y2) and swelling index (Y3) of the patches. In vitro release and swelling studies were carried out and the data were fitted to kinetic equations. RESULTS: The physicochemical, bioadhesive, and swelling properties of patches were found to vary significantly depending on the viscosity of the polymers and their combination. Patches showed an initial burst release preceding a more gradual sustained release phase following a nonfickian diffusion process. DISCUSSION: The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared, facilitated with the RSM.

A clinical perspective on mucoadhesive buccal drug delivery systems.

Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems.