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MicroRNAs (miRNAs) are small non-coding molecules that play a pivotal part in brain development and the processes of establishment and maintenance of dendrites and neurite outgrowth by modulating gene expression. Dysregulation of miRNAs has been linked with neurological disorders. Exogenous miRNAs are unstable in the plasma due to degradation by nucleases; hence, choosing a harmless and effective delivery mode is crucial in the quest for miRNA-based therapeutics to treat neurological disorders. This review aims to shed light on the emerging role of nanotechnology-based approaches using miRNAs to treat neurodegenerative disorders. Nanotechnology encompasses a broad spectrum of applications, one of which is its role in developing nanoscale drug delivery systems. Nanotechnology-based drug delivery systems have attracted the attention of researchers due to the superiority of this mode over conventional treatment systems in terms of their favorable attributes such as bio-compatibility, bio-degradability, extremely small size, and the ability to cross the blood-brain barrier. This review explores nanotechnology-based approaches using miRNAs highlighting the use of viral vectors as well as non-viral vectors (such as exosomes, liposome nanoparticles, gold and magnetic nanoparticles, dendrimer-based nanoparticles, polymeric nanoparticles) to treat neurodegenerative disorders.

Leukemoid Reaction (LR) signifies leukocytosis characterized by mature neutrophils. The incidence of LR is about 1 % among hospitalized patients. Mucormycosis is a rare, aggressive, fatal fungal infection that afflicts immune-compromised patients. This study discusses the case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection.

Sonochemistry under controlled conditions has proven effective in medicinal chemistry and drug development. It can substantially shorten reaction timelines from days or hours to minutes. A convenient one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives catalyzed by PTSA and benzenesulfonic acid in ethanol as solvent, under ultrasonic irradiation and without ultrasound irradiation at 50° C has been achieved successfully. These 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives synthesis were also accomplished using different solvents viz., Methanol, Ethanol, DCM, DMF, Acetonitrile and THF and PTSA as the catalyst. This method yielded the highest % synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives with PTSA as the catalyst in solvent ethanol. These reactions were also optimized for % of PTSA catalyst required to obtain the maximum yield of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazole derivatives with and without ultrasound irradiation at 50° C. Synthesis of 2,4,5-trisubstituted Imidazole derivatives reaction follows first-order rate kinetics while that of 1,2,4,5-tetrasubstituted Imidazole derivatives reaction follows the second-order rate kinetics. Furthermore, sonochemistry has higher yields, lower cost, easier workups, and higher purity than conventional thermal organic synthesis, which has lower yields, tedious workups, longer reaction periods, lower purity, and numerous byproducts. [ABSTRACT FROM AUTHOR]

Aim: In the present investigation, we have studied the inhibitory potential of a bioactive compound isolated from Rhus tripartite on Glucokinase (GK), Dipeptidyl Peptidase-IV (DPP-IV), alpha-glucosidase, and alpha-amylase enzymes. Materials and Methods: The plant leaves were subjected to Soxhlet extraction followed by qualitative phytochemical screening and the separation of active constituents by applying column chromatography. The obtained fraction was subjected to spectral analysis to identify the compound. Molecular docking followed by in vitro enzyme assays were used to study the inhibitory effect of the isolated compound. Results: The plant leaves were used for the extraction, and the identified compound was S-benzo[d]oxazol-2-yl 2-(piperazine-1-yl)ethanethioate, confirmed by spectral analysis. From in-silico ADMET analysis, the isolated compound displayed most drug-likeness features, and in molecular docking studies, it has developed many crucial hydrogen bonding and hydrophobic interactions with enzymes (PDB IDs: 1V4S, 2P8S, 3BAX, and 3WY2). An in vitro enzyme assay validated the virtual screening results of isolated compounds. Isolated compound at 250 μgm/mL displayed 96.29±2.56, 89.23±2.1, 72.72±0.75, and 69.76±0.85% activity against GK, DPP-IV, alpha-amylase, and alpha-glucosidase enzymes, respectively. Conclusion: Our study concluded that DM could be treated using an isolated compound after further in-vivo and in-vitro studies. [ABSTRACT FROM AUTHOR]

Cytokines are proteins that play a critical role in immune cells' development, maturation, and functional activities. For the first time, we have investigated the potential role of Terminalia arjuna as IL-4 and IL-13 modulators for preventing T1DM, i.e., autoimmune diabetes. It has been well documented that the stimulation of IL-4 and IL-13 can regulate the level of type 2 cytokines which can be maintained with the level of type 1 cytokines. The present study investigated gallic acid, arjunolic acid, luteolin, ellagic acid, and arjunone for their potential modulating activity of IL-4 and IL-13. The active amino acid residues identified for IL-4 are VAL51, HIS58, ASP87, THR30, GLN54, THR63, ARG64, LYS84, and GLU60. The active amino acid residues identified for IL-13 are H: GLU46, H: TRP47, H: GLN61, L: PHE98, L: VAL97, L: GLU162, L: THR163, H: ARG105, L: GLN38, L: ASP85, H: GLY42, L: GLY41, H: PRO41, H: TRP47, and L: PHE98. The phytoconstituents demonstrated better modulating activity towards IL-13 than IL-4. Luteolin displayed better potential for both IL-4 and IL-13, and therefore we concluded that it could be used to modulate the activity of IL-4 and IL-13 for the prevention of autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Breast Cancer (BC) is a worldwide prevalent carcinoma with varying growth rates. It is also a heterogeneous condition with several clinical manifestations. There is a guideline for effective screening of BC, but the mammograms that are obtained for the same often return false negatives or may not effectively diagnose BC, especially at the early stages. The mortality rates due to BC is also significant and efficient screening may reduce more than 30% of mortality. The assessment and accurate determination of tumour growth is difficult due to the substantial failures of screening BC cases. Aims and Objectives: This current study intends to introduce methods of screening BC using an Artificial Intelligence capable machine learning system, mainly for accurate and efficient detection of BC and assessing its prognostic outcomes. Materials and Methods: The study comprises a cohort of 120 BC patients aged between 50 and 65 years old. The study involves the development of serial mammograms for detection of in-vivo growth rate and further assessment of immunohistochemical staining. The study also facilitates the development of a machine learning model for detecting BC cases from serial mammograms and several other factors. Statistical analyses have been conducted for effective significance tests between the newly developed and existing methods. Results: The newly developed method proved to be successful in accurately assessing several aspects of the tumour, including size, stage, grade, mitotic score, type of histology, Nottinham Prognostic Index (NPI) and many more. The newly developed method is more significant than the existing one in assessing clinico-pathological characteristics. The newly developed method has shown significantly better prognostic ability than the existing one (p = 0.0284). Kaplan-Meier Survival Curve has been plotted to analyze the growth of the tumour with its prognosis. Conclusion: The study has effectively presented the development of a prognostic model for Breast Cancer patients with the application of machine learning algorithms, which can be utilized in the screening of breast cancers and proper management of the same to improve its prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of diabetes has increased since 1980. This increased prevalence is responsible for a significant number of deaths. The advancement of different drug classes has been a practical solution, but the required pharmacological effect is not achieved due to the disadvantages of less bioavailability. One of the drugs, Exenatide, is being considered in this study. This current study aims to develop a SEDDS for Exenatide to make it stable and increase its ability to permeate through the enterocytes to enhance its bioavailability and eventually improve blood glucose level status. The study further investigated the cytotoxicity of the whole system and compared the SEDDS effect on blood glucose level (BGL), stress biomarkers, and body weight with that of healthy rats, diabetic rats, and rats who were given Metformin. Materials and Methods: Exenatide is incorporated into the drug delivery system by ion-pairing method with sodium docusate (DOC) consisting of Labrafil, Cremophor-EL, propylene glycol and Capmul-PG. The study used rats for the classification of groups and analysis between the groups to find out the effect on BGL status, effect on stress biomarkers, and effect on body weight. The authors have performed the characterization, release, and cytotoxic studies of SEDDS to show that the validation of Exenatide administration is feasible using a drug delivery system. Result: The study has found that SEDDS brings effective improvement in BGL status (P<0.001), prevents weight loss as compared to all other groups (P<0.001), and reduces stress biomarkers significantly (P<0.001). The authors also studied the permeation process and cytotoxicity of SEDDS to validate its usage. Conclusion: Combining the findings, SEDDS (Exenatide and DOC) can be considered to manage diabetes type 2 effectively. However, there is a need to conduct more animal experiments and clinical trials. Unlike any previous study, detailed and analytically significant findings have been conducted and discussed in this current study to improve the management of diabetes type 2. [ABSTRACT FROM AUTHOR]

Context: Schiff bases (SB) is class of molecules that possess a wide spectrum of biological activities.Aims: Thus, the present study focuses on the synthesis and characterization of novel Schiff bases, which have not previously been explored in the literature and to investigate the synthesized compounds for anti-inflammatory and antioxidant activities with no or fewer side effects. Settings and Design: A group of 6-aryl substituted pyrimidine Schiff bases were synthesized by condensation of 6-phenyl pyrimidine 2-amine with different aldehydes. The synthetic compounds were studied for their in-vitro anti-inflammatory and antioxidant activities. Methods and Material: The characterization of the synthesized candidates was performed using 1H NMR, 13C NMR, IR, and MS. Computational study of designed compounds was done by OCHEM, Molinspiration cheminformatics, Datawarrior, and Swiss ADMET. DPPH assay was used to determine antioxidant activity and heat hemolysis method for anti-inflammatory activity.Results: All the test compounds showed dose-dependent inhibition, compound 5a showed consistent antioxidant and antiinflammatory activities. Computational studies predicted that none of the compounds can cross BBB, non-mutagenic, showed moderate activity against ion channel modulator, GPCR ligand, nuclear receptor, and enzymes. Conclusions: All the synthesized compounds, pyrimidine SB exhibited antioxidant and anti-inflammatory activities with less toxicity. Amongst the titled compounds, 5a and 5f were found to greatly influence the activity which may be due to the type of substituents present on the ring. The study carried out considered the three-dimensional nature of chemical structures that played an important part in ligand-receptor binding and assisted in providing an approach for further optimization of new leads. [ABSTRACT FROM AUTHOR]