Efficacy and safety of mavacamten in treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Aim: This meta-analysis was performed to assess the efficacy and safety of mavacamten in patients with hypertrophic cardiomyopathy. Methods & materials: A search was conducted using PubMed, Cochrane, and Scopus up to August 2022 for randomized studies reporting our pre-specified outcomes. Results: It was observed that mavacamten significantly improved New York Heart Association class (p < 0.009), Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (p = 0.02), post-exercise left ventricular outflow tract gradient (p < 0.00001), functional end point (p = 0.05), and lowered septal reduction therapy rates (p < 0.00001). However, there were no significant differences in the ≥1 severe adverse events, ≥1 treatment-emergent adverse events, left ventricular volume index, left ventricular filling pressure, left ventricular end-diastolic volume index, and peak oxygen uptake (pVO2). Conclusion: Future large-scale trials are required to confirm our results and determine the long-term benefits and risks of mavacamten use in these patients.

Mavacamten is a recently introduced medication that relaxes the heart muscle and is indicated for patients with hypertrophic cardiomyopathy (a disease in which parts of the heart become thick and stiff). To determine the effectiveness and safety of this drug, the results of clinical trials were combined in order to produce an overall estimate. Overall, it was observed that mavacamten improved most functional parameters related to the heart and demonstrated no significant increases in the number of side effects. This suggests the effectiveness and safety of mavacamten, although further trials are needed to confirm our results.

Treatment with Testosterone Therapy in Type 2 Diabetic Hypogonadal Adult Males: A Systematic Review and Meta-Analysis.

Testosterone replacement therapy (TRT) has been used to treat hypogonadal males with type 2 diabetes mellitus (T2DM) for a long time, despite variable results. This meta-analysis examines TRT's role in hypogonadal males with T2DM. The databases PubMed, Embase, and Google Scholar were searched for relevant RCTs and observational studies. Estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals were used to measure the effects of TRT (CIs). When compared to the placebo, TRT improves glycemic management by significantly reducing glycated hemoglobin (HBA1c) levels (WMD = -0.29 [-0.57, -0.02] p = 0.04; I2 = 89.8%). Additionally, it reduces the homeostatic model assessment levels of insulin resistance (WMD = -1.47 [-3.14, 0.19]; p = 0.08; I2 = 56.3%), fasting glucose (WMD = -0.30 [-0.75, 0.15]; p = 0.19; I2 = 84.4%), and fasting insulin (WMD = -2.95 [-8.64, 2.74]; however, these results are non-significant. On the other hand, HBA1c levels are significantly reduced with TRT; in addition, total testosterone levels significantly increase with testosterone replacement therapy (WMD = 4.51 [2.40, 6.61] p = 0.0001; I2 = 96.3%). Based on our results, we hypothesize that TRT can improve glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol levels while raising HDL cholesterol in hypogonadal type 2 diabetes patients. To this end, we recommend TRT for these patients in addition to standard diabetes care.

Cyclodextrin-Based Arsenal for Anti-Cancer Treatments.

Anti-cancer drugs are mostly limited in their use due to poor physicochemical and biopharmaceutical properties. Their lower solubility is the most common hurdle limiting their use upto their potential. In the recent years, the cyclodextrin (CD) complexation have emerged as existing approach to overcome the problem of poor solubility. CD-based nano-technological approaches are safe, stable and showed well in vivo tolerance and greater payload for encapsulation of hydrophobic drugs for the targeted delivery. They are generally chosen due to their ability to get self-assembled to form liposomes, nanoparticles, micelles and nano-sponges etc. This review paper describes a birds-eye view of the various CD-based nano-technological approaches applied for the delivery of anti-cancer moieties to the desired target such as CD based liposomes, niosomes, niosoponges, micelles, nanoparticles, monoclonal antibody, magnetic nanoparticles, small interfering RNA, nanorods, miscellaneous formulation of anti-cancer drugs containing CD. Moreover, the author also summarizes the various shortcomings of such a system and their way ahead.

Self-Assembly Polymeric Nano Micelles for the Futuristic Treatment of Skin Cancer and Phototoxicity: Therapeutic and Clinical Advancement.

In the last few years, the polymeric micelles played a major role as a drug carrier in nano-sized drug delivery system. The polymeric micelles are designed from synthetic block co-polymers and graft copolymers. In the mixed micelles, the bilayer lipid membrane and surfactants are used. Both micelles are in nano-sized and used to enhance the drug delivery to treat different diseases. In this review, we will discuss some examples from the literature included demonstrating the polymeric micelles used as drug-carriers in skin cancer treatment by using different drugs. We also summarized mixed micelles, polymeric micelles in skin drug delivery, various polymers, and techniques of polymeric micelles. These micelles may improve delivery of drug in the skin's targeted sites in specific and dermatological diseases like skin cancer, acne, and fungal infection. In the comparison of surfactant micelles, the polymeric micelles are more stable. Polymeric micelles act as a colloidal carrier for incorporating poorly water-soluble and amphiphilic drugs.

Development of coinage metal nanoclusters as antimicrobials to combat bacterial infections.

Infections from antibiotic-resistant bacteria have caused huge economic loss and numerous deaths over the past decades. Researchers are exploring multiple strategies to combat these bacterial infections. Metal nanomaterials have been explored as therapeutics against these infections owing to their relatively low toxicity, broad-spectrum activity, and low bacterial resistance development. Some coinage metal nanoclusters, such as gold, silver, and copper nanoclusters, can be readily synthesized. These nanoclusters can feature multiple useful properties, including ultra-small size, high catalytic activity, unique photoluminescent properties, and photothermal effect. Coinage metal nanoclusters have been investigated as antimicrobials, but more research is required to tap their full potential. In this review, we discuss multiple advantages and the prospect of using gold/silver/copper nanoclusters as antimicrobials.

Analytical Method Development and Validation of UV-visible Spectrophotometric Method for the Estimation of Vildagliptin in Gastric Medium.

BACKGROUND: Vildagliptin is an antidiabetic agent, belongs to the dipeptidyl peptidase IV (DPP-4) inhibitors. OBJECTIVE: The aim of investigation was to develop a simple UV-visible Spectrophotometric method for the determination of vildagliptin in its pure form and pharmaceutical formulations, further to validate the developed method. MATERIAL AND METHODS: Vildagliptin was estimated using UV-Visible double beam spectrophotometer at the wavelength of maximum absorption (210 nm) in acidic medium containing 0.1N HCl. The drug was characterized by melting point, Differential Scanning Calorimetry (DSC), and Fourier Transform Infra-Red (FTIR) techniques. The analysis of the drug was carried out by novel UV-Visible method which was validated analytical parameters like linearity, precision, and accuracy as per guidelines laid down by International Conference on Harmonization (ICH). RESULT: Melting point of drug was found 154°C which is corresponds to its actual melting range. Similarly by the interpretation of spectra the drug was confirmed. The linear response for concentration range of 5-60 µg/ml of vildagliptin was recorded with regression coefficient 0.999. The accuracy was found between 98-101%. Precision for intraday and interday was found to be 1.263 and 1.162 respectively, which are within the limits. To establish the sensitivity of the method, limit of detection (LOD) and limit of quantification (LOQ) were determined which were found to be 0.951 µg/ml and 2.513 µg/ml respectively. CONCLUSION: The UV method developed and validated for vildagliptin drug was found to be linear, accurate, precise and economical which can be used for the testing of its pharmaceutical formulations.

Development of Nasal Mucoadhesive Microspheres of Granisetron: A Potential Drug.

BACKGROUND: Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. OBJECTIVES: In this research mucoadhesive microspheres were developed in order to carry out the absorption of drug through nasal mucosa with the aim to improve therapeutic efficacy, avoid hepatic first pass metabolism and increase residence time. MATERIAL AND METHODS: Mucoadhesive microspheres of Granisetron using chitosan as polymer were prepared by emulsification cross-linking method to increase the residence time on the mucosa. The surface of prepared microspheres was characterized by SEM (Scanning electron microscopy) and evaluated for particle size, encapsulation efficiency, production yield, swelling ability, in-vitro mucoadhesion, in-vitro drug release and stability study. RESULT: Among all the formulations F6 with drug/polymer ratio of 1:3 displayed the best result. On drug release kinetic model study, all the formulations follow Zero order. Stability studies revealed that the microspheres kept at 25±2°C and 60±5% RH showed the maximum stability. CONCLUSION: After all the evaluation parameters and result obtained it can be said that these results confirmed the suitability of Granisetron mucoadhesive chitosan microspheres for nasal delivery system.

Purification and separation of ultra-small metal nanoclusters.

Metal nanoclusters (NCs) are ultra-small nanoparticles intermediate in size between small molecule complexes and nanoparticles. NCs with tunable surface functionality feature unique physical and chemical properties, however these properties are frequently compromised by the presence of undesired components such as excess ligands or mixtures of NCs. In a typical synthesis process, different NCs can be formed with varying numbers of metal atoms and/or ligands, and even NCs with the same number of metal atoms and ligands can have different spatial structures. The separation of pure NCs is important because different species have distinct optical and catalytic behavior. However, NCs can be difficult to purify or separate for a range of reasons. In this review, we discuss established and emerging approaches for NC purification/separation, with a focus on choosing the appropriate method depending on NC and application.

Effective detection of bacteria using metal nanoclusters.

Antibiotic-resistant bacterial infections cause more than 700 000 deaths each year worldwide. Detection of bacteria is critical in limiting infection-based damage. Nanomaterials provide promising sensing platforms owing to their ability to access new interaction modalities. Nanoclusters feature sizes smaller than traditional nanomaterials, providing great sensitive ability for detecting analytes. The distinct optical and catalytic properties of nanoclusters combined with their biocompatibility enables them as efficient biosensors. In this review, we summarize multiple strategies that utilize nanoclusters for detection of pathogenic bacteria.

Developing Photosensitizer-Cobaloxime Hybrids for Solar-Driven H2 Production in Aqueous Aerobic Conditions.

Developing photocatalytic H2 production devices is the one of the key steps for constructing a global H2-based renewable energy infrastructure. A number of photoactive assemblies have emerged where a photosensitizer and cobaloxime-based H2 production catalysts work in tandem to convert light energy into the H-H chemical bonds. However, the long-term instability of these assemblies and the need for hazardous proton sources have limited their usage. Here, in this work, we have integrated a stilbene-based organic dye into the periphery of a cobaloxime core via a distinct axial pyridine linkage. This strategy allowed us to develop a photosensitizer-catalyst hybrid structure with the same molecular framework. In this article, we have explained the detailed procedure of the synthesis of this hybrid molecule in addition to its comprehensive chemical characterization. The structural and optical studies have exhibited an intense electronic interaction between the cobaloxime core and the organic photosensitizer. The cobaloxime was active for H2 production even in the presence of water as the proton source. Here, we have developed a simple airtight system connected with an online H2 detector for the investigation of the photocatalytic activity by this hybrid complex. This photosensitizer-catalyst dyad present in the experimental setup continuously produced H2 once it was exposed in the natural sunlight. This photocatalytic H2 production by the hybrid complex was observed in aqueous/organic mixture media in the presence of a sacrificial electron donor under complete aerobic conditions. Thus, this photocatalysis measurement system along with the photosensitizer-catalyst dyad provide valuable insight for the development of next generation photocatalytic H2 production devices.

Silver Nanoclusters Encapsulated into Metal-Organic Frameworks for Rapid Removal of Heavy Metal Ions from Water.

Metal nanomaterials have been reported as effective absorbents for the removal of pollutants in the water system, but the release of ions from these nanomaterials brings another concern. Herein, silver nanoclusters (AgNCs) were encapsulated in porous metal-organic frameworks of ZIF-8 (MOF-AgNCs). Compared to AgNCs, the release of Ag+ significantly decreases from MOF-AgNCs, indicating that the product presents a lower threat to the environment. The MOF-AgNCs were employed for the rapid removal of heavy metals, such as Pb2+ and Mn2+, from water. The mechanism and removal efficiencies were investigated.

Cationic red emitting fluorophore: A light up NIR fluorescent probe for G4-DNA.

Guanine (G) quadruplexes (G4) are nucleic acid secondary structures formed by G-rich sequences, commonly found in human telomeric and oncogene-promoter regions, have emerged as targets for regulation of multiple biological processes. Considering their importance, targeting the G-quadruplex structure with small molecular binders is extremely pertinent. In this work, red emitting water soluble fluorophores bearing push-pull substituents were synthesized and examined for their interaction with human telomeric G4 and duplex (ds) -DNAs. The presence of a strong electron donating (dimethylamino) and electron withdrawing (cationic pyridinium) groups linked through a conjugated double bond helps in water solubility and enabling the emission in the near IR region (>700-nm). Binding of this cationic dye to the G4-DNA yields multiple-fold emission enhancement (~70 fold with G4-DNA vs. ~7 fold with ds-DNA) along with hypsochromic wavelength shifts (35 nm with G4-DNA and 8 nm with ds-DNA). The remarkable emission changes, ~2-4 fold enhanced binding efficiency noted with the antiparallel conformation of G4-DNA indicates preferential selectivity over ds-DNA. The molecular docking and dynamics studies of the ligands with duplex and G4-DNA were performed, and they provide insights into the mode of binding of these dyes with G4-DNA and supplement the experimental observations.

Comprehensive review of the role of acrylic acid derivative polymers in floating drug delivery system.

In the development of drug delivery systems, an oral drug delivery system is the preferred route of drug administration. Many components play an important role in developing a drug delivery system. Amongst those components, polymers have evolved with these systems. Macromolecule compounds consisting of many monomer units which are joined to each other by different bonds are known as polymers. For drugs that are absorbed primarily in the upper gastrointestinal tract, floating drug delivery systems offer an additional advantage. The purpose behind this review was to focus on different types of floating drug delivery systems and different types of polymers used in floating drug delivery systems, focusing on acrylic acid derivatives and their applications. In this review, the main emphasis is on acrylic acid derivative polymers, their formulation and grades, and various patents on these types of polymers. Based on the literature survey, mainly 2 types of polymers are used in this drug delivery system; i.e., natural and synthetic. Examples of natural polymers are xanthan gum, guar gum or chitosan, and synthetic polymers include acrylic acid derivatives and hydroxylpropyl methylcellulose (HPMC). Eudragit and Carbopol are the most widely used acrylic acid derivatives.

Emission and Color Tuning of Cyanostilbenes and White Light Emission.

White-light-emitting diodes are energy efficiency replacement of conventional lighting sources. Herein, we report the luminescent behavior of three simple cyanostilbenes with triphenylamine-donating groups bearing different electron-withdrawing groups (phenyl, pyridyl, and p-nitrophenyl) in a common donor (D)-π-acceptor (A) α-cyanostilbene construct along with their thermal and electrochemical properties. The density functional theory (DFT) studies reveal that aggregation-induced emission characteristic feature of the D-π-A dyes is inversely proportional to the intramolecular charge transfer (ICT) effect, that is, phenyl-and pyridyl-substituted compounds show characteristic aggregation-induced emission in water, whereas the ICT effect is dominant for the nitro derivative. The extent of ICT and the solvatochromic emission shifts, from blue to red, depend on the strength of the electron-withdrawing group. White luminescence and tunable emission colors are obtained by careful admixtures of these cyanostilbenes bearing triphenylamines. The results rationalized through DFT and time-dependent DFT calculations follow a consistent trend with the energy levels measured from the electrochemical and optical studies. Thermogravimetric analysis and differential scanning calorimetry studies showed excellent thermal stability of the compounds. The scanning electron microscopy and dynamic light scattering measurements were performed to reveal the formation of aggregates. This strategy involving synthetically simple and structurally similar molecules with different emission properties has potential applications in the fabrication of multicolor and white-light-emitting materials.

Persistence of Pendimethalin in/on Wheat, Straw, Soil and Water.

Pendimethalin, a dinitroaniline group of organic herbicide compounds used as pre emergence weed control in wheat, onion and soyabean crops in India. The experiments were designed to study the harvest time residues of pendimethalin in wheat grain and straw its dissipation behaviour in soil and water. At harvest time, the residues of pendimethalin in wheat grain and straw were found to be below determination limit of 0.001 mg kg(-1) following single application of the herbicide at the rate of 1 (T1/single dose) and 2 (T2/double dose) kg a.i. ha(-1). Soil samples from the field were collected periodically and analysed by GC-ECD system. In soil, initial deposits of 4.069 and 10.473 mg kg(-1) of pendimethalin persisted up to 90 days and dissipation followed first order kinetics with half life period of 12.03 days in T1 and 13.00 days in T2. Residues of pendimethalin studied in water under laboratory conditions at 0.5 (T1) and 1.0 (T2) mg L(-1) levels persisted up to 90 days. Dissipation kinetics followed first order kinetics with half-life values of 12.70 and 13.78 days at single and double dose, respectively. Limit of determination in grain, straw and soil were 0.001 mg kg(-1) and in water was 0.001 mg L(-1). Application of the herbicide is considered quite safe from consumer and environmental point of view.

Fate of thiodicarb and its metabolite methomyl in sandy loam soil under laboratory conditions.

Fate of thiodicarb and its major metabolite in sandy loam soil were studied by applying thiodicarb (Larvin 75 WP) at 500 and 1000 g a. i. ha(-1) under laboratory conditions. Samples drawn periodically were analysed on GC-FTD equipped with capillary column. The average initial deposits of total thiodicarb (thiodicarb and methomyl) were 0.025 and 0.035 mg kg(-1) at single and double dosages, respectively. Residues of thiodicarb reached below the determination level (BDL) of 0.005 mg kg(-1) after 15 days. Half-life periods for total thiodicarb were calculated to be 5.90 and 8.29 days at two doses, respectively, following first-order kinetics.

Determination of residues of fipronil and its metabolites in cauliflower by using gas chromatography-tandem mass spectrometry.

Fipronil is a widely used insecticide with a well-described toxicological pathway. Recently it has been widely used in India to control vegetable pests. The present study has been carried out to observe the persistence pattern of fipronil and its metabolites-fipronil sulfone, fipronil sulfide, fipronil desulfinyl in cauliflower and soil so as to know the potential risk if any to consumers and environment. Fipronil was applied @ 56 g a.i. ha(-1). Samples of cauliflower and soil were collected periodically; processed using QuEChERS method and analyzed by GCMS/MS. In cauliflower, residues of fipronil and its metabolites reached below detectable level before 30 days of application whereas in soil about 95% of total fipronil residues got degraded within same time period. Washing and washing followed by cooking or boiling was found effective in reducing residues. A safe waiting period of 15 days is therefore suggested before consuming cauliflower.