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Inhibition of aldose reductase (AR) could be a beneficial strategy for managing diabetes-associated complications. Trigonella foenum-graecum (TFG) is used around the globe as a traditional medicine for the management of diabetes. Our study aimed to assess the potential of TFG phytocompounds as inhibitors of AR in the context of diabetes-related complications. Our research work employed molecular docking, density functional theory (DFT) and molecular dynamics (MD) to evaluate the efficacy of TFG compounds. The study compared the predictive power of AutoDock and AutoDock Vina docking software and found that AutoDock Vina performs better in ranking and discriminating actives and decoys. The research identified five compounds as potential AR inhibitors from fifty-eight reported TFG phytoconstituents. Tigogenin and Gitogenin stood out as the most promising AR inhibitors. The electronic properties of the compounds were analysed through DFT studies and provided insights into their binding potential. Finally, the results of MD simulations indicated that Tigogenin and Gitogenin bound robustly with AR throughout the simulation period. This study predicted the AR inhibitory potential of TFG compounds for managing diabetes-associated complications and supports further drug development from TFG. The benchmarking approach used in this study improves the accuracy and dependability of bioactivity prediction.

Traditional healers have used the shrub Calotropis procera (CP) for many years for various therapies. The present study investigated the bioactive constituents of ethanolic extract of CP leaf and dried latex using gas chromatography-mass spectrometry and Fourier transforms infrared spectroscopy. The identification and characterization of the compounds were confirmed by examining the constituents' mass spectrum fragmentations and FT-IR spectra and comparing the results with those in the literature. The tail-flick method was used to investigate the analgesic properties of the extract and its anti-inflammatory activities using a rat model of formalin-induced oedema. Acute oral toxicity in rats was studied per OECD recommendations. Twenty male rats were divided into four groups and received an ethanolic extract of the leaves and dried milky sap of CP (200 mg/Kg) in groups 1, 2, and 3. Group 4 rats were administered aspirin 50 mg/kg as a positive control. The CP dried latex extract has the highest content of lupeol and its acetate derivative compared to its leaf extract. The CP dried latex extract inhibited inflammation more significantly than the ethanolic leaf extract and the drug indomethacin at a higher dosage (200 mg/kg). The ethanolic extracts showed analgesia comparable to aspirin. It suggests that fatty acids and their esters, particularly ethyl linoleate (8.96%), ethyl palmitate (7.99%), ethyl linoleate (6.98%), and palmitic acid (5.18%), may be valuable biomarkers for characterizing leaf and latex samples and describing the medicinal potential of CP.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.

Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) partial agonists or antagonists, also termed as selective PPAR-γ modulators, are more beneficial than full agonists because they can avoid the adverse effects associated with PPAR-γ full agonists, such as weight gain and congestive heart disorders, while retaining the antidiabetic efficiency. In this study, we designed and synthesized new benzylidene-thiazolidine-2,4-diones while keeping the acidic thiazolidinedione (TZD) ring at the center, which is in contrast with the typical pharmacophore of PPAR-γ agonists. Five compounds (5a–e) were designed and synthesized in moderate to good yields and were characterized using spectral techniques. The in vivo antidiabetic efficacy of the synthesized compounds was assessed on streptozotocin-induced diabetic mice using standard protocols, and their effect on weight gain was also studied. Molecular docking and molecular dynamics (MD) simulation studies were performed to investigate the binding interactions of the title compounds with the PPAR-γ receptor and to establish their binding mechanism. Antidiabetic activity results revealed that compounds 5d and 5e possess promising antidiabetic activity comparable with the standard drug rosiglitazone. No compound showed considerable effect on the body weight of animals after 21 days of administration, and the findings showed statistical difference (p

In continuation of our reserach for synthesizing heterocyclic derivatives with a broad range of biological activities, the current research was performed to synthesize 3β-hydroxypregn-5-ene-20-one derivatives of coumarin, isoxazole, pyrazole, pyridine and pyrimidine and screen for antitumor activity. Synthesis of amino-thiopephen derivatives (1a-1b) was performed through reaction of 3β-hydroxypregn-5-ene-20-one with ethyl cyanoacetate or malononitrile and sulphur. 3β-Hydroxypregn-5-ene-20-one was reacted with ethyl cyanoacetate in the presence of hydrazine, urea or thiourea to obtain aminopyrazole (3), aminopyrimidine (4a-4b) derivatives, respectively. The amino-thiophene derivatives (1a-1b) further reacted with either phenylisothiocyanate or benzoylisothiocyanate to form fused thienopyrimidine derivatives (5a-5d). The products 1a and 1b were also treated with ethyl cyanoacetate to afford cyanoacetamidothiophene derivatives (6a-6b) which were converted to fused thienopyridone derivatives (7a-7b) through cyclization reaction. The compounds 6a and 6b were allowed to react with different carbonyl compounds including salicyaldehyde, cyclopentanone-sulphur mixture, acetylacetone and malonaldehyde to prepare coumarin (8a-8b), cyclopentylthiophene (9a-9b) and 2-pyridinone (10a-10d) derivatives respectively. Furthermore, the reactions of hydroxylamine hydrochloride and benzoylacetonitrile with the compounds 6a-6b separately afforded new aminoisoxazole (12a-12b) and phenylpyridone (14a-14b) derivatives, respectively. The structures of new products were established through IR, 1H NMR, 13C NMR spectroscopic and mass spectrometric analysis. The synthesized compounds (1a-1b to 14a-14b) displayed in-vitro antitumor activity against human cell-lines, including MCF-7 (breast adenocarcinoma), SF-268 (CNS cancer) and NCI-H460 (non-small lung cancer cell). The results suggested that all the screened products exhibited cell growth inhibitory activity in a dose-dependents manner. However, the compound 12a showed highest level of inhibition against all three cell-lines.

The purpose of immunization is the effective cellular and humoral immune response against antigens. Several studies on novel vaccine delivery approaches such as micro-particles, liposomes & nanoparticles, etc. against infectious diseases have been investigated so far. In contrast to the conventional approaches in vaccine development, a virosomes-based vaccine represents the next generation in the field of immunization because of its balance between efficacy and tolerability by virtue of its mechanism of immune instigation. The versatility of virosomes as a vaccine adjuvant, and delivery vehicle of molecules of different nature, such as peptides, nucleic acids, and proteins, as well as provide an insight into the prospect of drug targeting using virosomes. This article focuses on the basics of virosomes, structure, composition formulation and development, advantages, interplay with the immune system, current clinical status, different patents highlighting the applications of virosomes and their status, recent advances, and research associated with virosomes, the efficacy, safety, and tolerability of virosomes based vaccines and the future prospective.

This review aims to provide a thorough examination of the benefits, challenges, and advancements in utilizing lipids for more effective drug delivery, ultimately contributing to the development of innovative approaches in pharmaceutical science. Lipophilic drugs, characterized by low aqueous solubility, present a formidable challenge in achieving effective delivery and absorption within the human body. To address this issue, one promising approach involves harnessing the potential of lipids. Lipids, in their diverse forms, serve as carriers, leveraging their unique capacity to enhance solubility, stability, and absorption of these challenging drugs. By facilitating improved intestinal solubility and selective lymphatic absorption of porously permeable drugs, lipids offer an array of possibilities for drug delivery. This versatile characteristic not only bolsters the pharmacological efficacy of drugs with low bioavailability but also contributes to enhanced therapeutic performance, ultimately reducing the required dose size and associated costs. This comprehensive review delves into the strategic formulation approaches that employ lipids as carriers to ameliorate drug solubility and bioavailability. Emphasis is placed on the critical considerations of lipid type, composition, and processing techniques when designing lipid-based formulations. This review meticulously examines the multifaceted challenges that come hand in hand with lipid-based formulations for lipophilic drugs, offering an insightful perspective on future trends. Regulatory considerations and the broad spectrum of potential applications are also thoughtfully discussed. In summary, this review presents a valuable repository of insights into the effective utilization of lipids as carriers, all aimed at elevating the bioavailability of lipophilic drugs.

Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.

Cancer progression is strongly affected by epigenetic events in addition to genetic modifications. One of the key elements in the epigenetic control of gene expression is histone modification through acetylation, which is regulated by the synergy between histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are thought to offer considerable potential for the development of anticancer medications, particularly when used in conjunction with other anticancer medications and/or radiotherapy. Belinostat (Beleodaq, PXD101) is a pan-HDAC unsaturated hydroxamate inhibitor with a sulfonamide group that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of refractory or relapsed peripheral T-cell lymphoma (PTCL) and solid malignancies or and other hematological tissues. This drug modifies histones and epigenetic pathways. Because HDAC and HAT imbalance can lead to downregulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by belinostat indirectly promotes anti-cancer therapeutic effect by provoking acetylated histone accumulation, re-establishing normal gene expressions in cancer cells and stimulating other routes such as the immune response, p27 signaling cascades, caspase 3 activation, nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) degradation, cyclin A (G2/M phase), cyclin E1 (G1/S phase) and other events. In addition, belinostat has already been discovered to increase p21WAF1 in a number of cell lines (melanoma, prostate, breast, lung, colon, and ovary). This cyclin-dependent kinase inhibitor actually has a role in processes that cause cell cycle arrest and apoptosis. Belinostat's clinical effectiveness, comprising Phase I and II studies within the areas of solid and hematological cancers, has been evidenced through several investigative trials that have supported its potential to be a valuable anti-cancer drug. The purpose of this research was to provide insight on the specific molecular processes through which belinostat inhibits HDAC. The ability to investigate new therapeutic options employing targeted therapy and acquire a deeper understanding of cancer cell abnormalities may result from a better understanding of these particular routes.

Introduction: Given the severity of the condition and the increasing number of patients, developing effective therapies for Alzheimer's disease has become a significant necessity. Aggregation of Amyloid-Beta (Aβ) plaques and Tau Protein Tangles in the brain's nerve tissue are two of the most histopathological/pathophysiological symptoms. Another important element involved in the etiology of Alzheimer's disease is the reduction in acetylcholine (ACh) levels in the brain. Currently available medications for Alzheimer's disease treatment, such as cholinesterase inhibitors and an antagonist of the N-methyl-d-aspartate receptor, can temporarily reduce dementia symptoms but not stop or reverse disease development. In addition, several medicinal plants have been shown to diminish the degenerative characteristics associated with Alzheimer's disease, either in its crude form or as isolated chemicals. Aim: This review summarises the results from previous studies that reflect an array of novel therapies underway in various phases of clinical trials. Many are discontinued due to non-adherence to the designed endpoints or the surfacing of unavoidable side effects. The present piece of article focuses on the approved drugs for the treatment of Alzheimer's disease and their related mode of action as well as the promising therapies for the treatment of the said disease. Special attention has been placed on the researched herbal drugs, with the pipeline of novel therapies underway in various phases of clinical trials. Result: The current article includes a list of approved pharmaceuticals for treating Alzheimer's disease, prospective therapies for the illness's treatment, and a pipeline of novel therapies in various stages of clinical trials. Conclusion: The results suggest that the drugs under clinical trials may open new pathways for the effective treatment of patients with Alzheimer's disease while improving their quality of life.

Purpose: The primary goal of this research is to improve the bioavailability and efficacy of Sumatriptan succinate by incorporating it in the mucoadhesive film for the treatment of migraine. Mucoadhesive film offers an excellent substitute to deliver the drug in the systemic circulation and eliminate the chance of first-pass metabolism. Method: Using central composite design (CCD), various formulations were created by incorporating polymer, plasticizer, and water, and an optimized preparation was created using statistical screening. The optimization has been performed by applying a 34 factorial method based on dependent variables such as Drug content (%), Swelling index (%), Folding endurance (Number of times), and Mucoadhesive strength (g). Results: The actual experimental values obtained were compared with those predicted by the mathematical models. Formulation S9 was selected as an optimized formulation because it showed the lowest standard deviation between predicted and actual values compared to other formulations. In the case of the S9 formulation, approximately 77.12% of the drug was released within 24 h, but initially, it showed burst release. In addition, the in-vitro release of pure drug suspension showed 99.32% drug release within 2 h. That signified that the developed formulation provides sustained release due to presence of grafted co-polymer. Conclusion: Formulation holding drug-loaded grafted film showed decent sustained and controlled drug release characteristics compared to a pure drug suspension. S9 formulation showed better results than other formulations in drug content, swelling index, folding endurance, and mucoadhesive strength, which is further used to treat migraine.

Objective: This study describes the development of a cost-effective and sensitive immunosensor for rapid detection of the dengue virus (DENV) antigen in human plasma. Methods: Screen-printed carbon electrodes (SPCEs) were used to fabricate the immunosensor by immobilizing the DENV antibodies to its surface using 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDC/s-NHS) as linker. The detection of the antigen–antibody interaction was achieved by linear sweep voltammetry (LSV) using potentiostat instrument and a sensor connector. The developed method was validated as per the ICH guidelines for linearity, sensitivity and accuracy. Results: The developed immunosensors showed excellent sensitivities in detecting the DENV antigens in both phosphate buffer saline (PBS) maintained at pH 7.4 as well as diluted human plasma. The limit of detection (LOD) values obtained in PBS was 0.11 nM; whereas in human plasma, it was calculated to be 0.16 nM. Good linearity was obtained for both PBS and human plasma over a wide range of concentrations showing promising applications of the immunosensor in both qualitative and quantitative detection of dengue virus antigen. Also, the developed immunosensor was able to detect the dengue antigen in 5 min showing rapid detection. Conclusion: A sensitive, reliable and cost-effective biosensor was developed which was able to detect the dengue virus antigen selectively and rapidly.

Objectives: Preliminary diagnosis of hepatitis B is performed by measuring the levels of serological markers using enzyme-linked immunosorbent assay (ELISA). Errors in diagnosis of the disease using serum markers might occur due to the presence of metallic salts in diagnostic samples. The present study was designed to evaluate the effects of various metal ions on the diagnosis of recombinant hepatitis B surface antigen (HBsAg). Methods: A simple step sandwich ELISA technique was used to evaluate the effects of metal ions on the diagnosis of HBsAg. Further, the zeta potential, electrical conductivity and redox potential of solutions with proteins and metal salts were measured to evaluate the interaction of these metal ions with the protein. Results: The results showed that recombinant HBsAg significantly interacted with the tested metal ions, with lithium ion showing the highest interaction, followed by barium, aluminium, and nickel as the percent decrease in the free HBsAg concentration in presence of these metal ions were found to be 95.5, 94.1, 93.5, and 91.6%, respectively. Zeta potential of the protein in reaction mixture also changed considerably and marked decrease in the concentration of free HBsAg was observed. This decrease in the concentration of free HBsAg resulted into error in the ELISA test which was negative in presence of these metal ions due to strong interaction with the HBsAg protein. Conclusions: The findings of this study clearly demonstrated that the presence of metal ions in pathological samples can result in interaction with the antigen leading to possible diagnostic errors.

This study was performed to evaluate phytochemical composition of Khaya senegalensis stem bark and Azadirachta indica leaf hydroethanolic (80%) extracts using GC-MS technique as a tentative identification method and screen for antioxidant and antidiabetic properties in Wistar rats. Diabetes was induced by intraperitoneal injection of alloxan (150 mg/kg·bw). Animals were divided into groups of six and treated by extracts (400 mg/kg·bw) for 28 days. The results compared with positive and negative control groups of animals. After treatment, blood samples were collected to determine the blood glucose level, lipid profile, liver and kidney function markers, and DPPH free radical scavenging activity was evaluated. Phytochemical investigations revealed that extracts were enriched with a wide range of secondary metabolites such as phenols, saponins, triterpenes, alkaloids, flavonoids, sterols, fatty acids, siloxane derivatives, and anthraquinones in diverse concentrations with reported antioxidant and antidiabetic properties. Biological screening results indicated that both extracts exhibited free-radical scavenging property in DPPH screening, and in that, K. senegalensis stem bark extract (91 ± 0.02%) showed greater reduction than A. indica leaf extract (55 ± 0.03%), with an IC50 of 0.023 ± 0.03 g/mL, which was lower than the reference drug propylgallate (0.077 ± 0.03 g/mL). Both the extracts remarkably reduced the blood glucose concentration in diabetic rats (p

Studies based on the interaction of metals with proteins resulted in the development of promising metal-based compounds with encouraging medicinal potential. This study was aimed to utilize FT-IR and UV-Vis spectroscopic techniques to analyze the interactions of biologically significant metal ions, such as Al3+, Ni+2, and Cu+, with bovine serum albumin (BSA). Different concentrations of metal ions were interacted with BSA, and the complexes were analyzed using the two techniques. The change in the BSA secondary structure components such as β-sheet, β-antiparallel, α-helix, β-turn, and random coil were analyzed using second derivative resolution enhancement. The FT-IR spectroscopy suggested a marked decrease in the C=O stretching (corresponding to amide I) and C=N stretching (corresponding to amide II) intensities. Interestingly, upon complexation, a marked reduction (22.58–29.03%) in the α-helical component was observed with a considerable increase in the random coil component. The intensity of the absorption peak of BSA obtained using UV was observed to increase consecutively as the concentration of Cu+, Al3+, and Ni2+ ions increased. The binding constants for the BSA-Cu+, BSA-Ni+2, and BSA-Al+3 complexes were calculated to be 3.46 × 104 M−1, 1.28 × 104 M−1, and 2.08 × 104 M−1, respectively. It was concluded that the binding interaction decreased in the order Cu+ > Al3+ > Ni2+. These findings were similar to our previous findings using affinity capillary electrophoresis (ACE). Therefore, it can be inferred that the FT-IR and UV techniques might be utilised effectively to assess the metal-protein interaction and can have wide application in routine analysis. These techniques have several advantages in being simple, easy-to-perform, rapid, and affordable over other high-end techniques.

Objectives: We performed a virtual screening of olive secoiridoids of the OliveNetTM library to predict SARS-CoV-2 PLpro inhibition. Benchmarked molecular docking protocol that evaluated the performance of two docking programs was applied to execute virtual screening. Molecular dynamics stability analysis of the top-ranked olive secoiridoid docked to PLpro was also carried out. Methods: Benchmarking virtual screening used two freely available docking programs, AutoDock Vina 1.1.2. and AutoDock 4.2.1. for molecular docking of olive secoiridoids to a single PLpro structure. Screening also included benchmark structures of known active and decoy molecules from the DEKOIS 2.0 library. Based on the predicted binding energies, the docking programs ranked the screened molecules. We applied the usual performance evaluation metrices to evaluate the docking programs using the predicted ranks. Molecular dynamics of the top-ranked olive secoiridoid bound to PLpro and computation of MM-GBSA energy using three iterations during the last 50 ps of the analysis of the dynamics in Desmond supported the stability prediction. Results and discussions: Predictiveness curves suggested that AutoDock Vina has a better predictive ability than AutoDock, although there was a moderate correlation between the active molecules rankings (Kendall's correlation of rank (τ) = 0.581). Interestingly, two same molecules, Demethyloleuropein aglycone, and Oleuroside enriched the top 1 % ranked olive secoiridoids predicted by both programs. Demethyloleuropein aglycone bound to PLpro obtained by docking in AutoDock Vina when analyzed for stability by molecular dynamics simulation for 50 ns displayed an RMSD, RMSF

Next to Alzheimer’s disease, Parkinson’s disease constitutes the second most widespread neurological disorder, primarily affecting the older population. Its symptoms are noticeable with advancing age including tremors, postural imbalance, and slow movements, and over time, these symptoms get aggravated, progressing to osteoporosis, osteopenia, and risk of fractures. These symptoms correlate to low bone density and hence weakened bones; thus, vitamin D proves to be an intricate component of the pathogenesis of the disease. Moreover, lower serum concentrations of vitamin D have been found in diseased subjects. Supplementation with vitamin D can retard the aggravation of non-motor as well as motor symptoms of Parkinson’s disease that include cognitive improvement along with the decline in risk of fractures. Also, vitamin D is extremely crucial for brain functioning, targeting dopaminergic neurons, and almost the entire functioning of the brain is affected. However, further exploration is required to determine the toxic dose of vitamin D in Parkinson’s subjects. This “sunshine vitamin” surely can be a ray of sunshine for neurologically diseased subjects.

Targeting SARS-CoV-2 papain-like protease using inhibitors is a suitable approach for inhibition of virus replication and dysregulation of host anti-viral immunity. Engaging all five binding sites far from the catalytic site of PLpro is essential for developing a potent inhibitor. We developed and validated a structure-based pharmacophore model with 9 features of a potent PLpro inhibitor. The pharmacophore model-aided virtual screening of the comprehensive marine natural product database predicted 66 initial hits. This hit library was downsized by filtration through a molecular weight filter of ≤ 500 g/mol. The 50 resultant hits were screened by comparative molecular docking using AutoDock and AutoDock Vina. Comparative molecular docking enables benchmarking docking and relieves the disparities in the search and scoring functions of docking engines. Both docking engines retrieved 3 same compounds at different positions in the top 1 % rank, hence consensus scoring was applied, through which CMNPD28766, aspergillipeptide F emerged as the best PLpro inhibitor. Aspergillipeptide F topped the 50-hit library with a pharmacophore-fit score of 75.916. Favorable binding interactions were predicted between aspergillipeptide F and PLpro similar to the native ligand XR8-24. Aspergillipeptide F was able to engage all the 5 binding sites including the newly discovered BL2 groove, site V. Molecular dynamics for quantification of Cα-atom movements of PLpro after ligand binding indicated that it exhibits highly correlated domain movements contributing to the low free energy of binding and a stable conformation. Thus, aspergillipeptide F is a promising candidate for pharmaceutical and clinical development as a potent SARS-CoV-2 PLpro inhibitor.

The expeditious advancement of Alzheimer’s Disease (AD) is a threat to the global healthcare system, that is further supplemented by therapeutic failure. The prevalence of this disorder has been expected to quadrupole by 2050, thereby exerting a tremendous economic pressure on medical sector, worldwide. Thus, there is a dire need of a change in conventional approaches and adopt a novel methodology of disease prevention, treatment and diagnosis. Precision medicine offers a personalized approach to disease management, It is dependent upon genetic, environmental and lifestyle factors associated with the individual, aiding to develop tailored therapeutics. Precision Medicine Initiatives are launched, worldwide, to facilitate the integration of personalized models and clinical medicine. The review aims to provide a comprehensive understanding of the neuroinflammatory processes causing AD, giving a brief overview of the disease interventions. This is further followed by the role of precision medicine in AD, constituting the genetic perspectives, operation of personalized form of medicine and optimization of clinical trials with the 3 R’s, showcasing an in-depth understanding of this novel approach in varying aspects of the healthcare industry, to provide an opportunity to the global AD researchers to elucidate suitable therapeutic regimens in clinically and pathologically complex diseases, like AD.

Mitochondria play a crucial part in the cell's ability to adapt to the changing microenvironments and their dysfunction is associated with an extensive array of illnesses, including cancer. Mitochondrial dysfunction has been identified as a potential therapeutic target for cancer therapy. The objective of this article is to give an in-depth analysis of cancer treatment that targets the mitochondrial genome at the molecular level. Recent studies provide insights into nanomedicine techniques and theranostic nanomedicine for mitochondrial targeting. It also provides conceptual information on mitochondrial biomarkers for cancer treatment. Major drawbacks and challenges involved in mitochondrial targeting for advanced cancer therapy have also been discussed. There is a lot of evidence and reason to support using nanomedicine to focus on mitochondrial function. The development of a delivery system with increased selectivity and effectiveness is a prerequisite for a theranostic approach to cancer treatment. If given in large amounts, several new cancer-fighting medicines have been created that are toxic to healthy cells as well. For effective therapy, a new drug must be developed rather than an old one. When it comes to mitochondrial targeting therapy, theranostic techniques offer valuable insight.

Type 2 diabetes mellitus (T2D) is a metabolic disorder that knows no boundaries and is spread across the globe. It is one of the most widely spread metabolic disorder, which has now been described as a ‘lifestyle’ disease. According to the recent study conducted by International Diabetes Federation, the number of diabetic patients will rise from 463 million to 700 million by the year 2045. Conventional therapies often fail to define clear parameters and did not provide early detection in case of diabetes and pre-diabetes. Due to the limitations associated with these therapies, inclination of research is now focused on developing methods or exploring pathways which can overcome these hurdles. Considering these factors, protein tyrosine phosphatase is considered as a promising molecular level legitimate therapeutic target and is known to negatively regulate leptin and insulin signaling pathways. It has shown to be effective in the management of diabetes mellitus in various in vitro and in vivo studies. Various PTP-1B inhibitors have been studied which had shown promising results in the management of diabetes mellitus and associated complications as well. These inhibitors act by increasing insulin sensitivity by inhibiting PTP-1B mediated insulin pathway. In this article we will review the underlying mechanism of protein tyrosine phosphatase and its inhibitors by various PTP 1-B inhibitors for the management of diabetes mellitus and will further throw some light on the challenges and development of these inhibitors.

Dementia is defined as a gradual cognitive impairment that interferes with everyday tasks, and is a leading cause of dependency, disability, and mortality. According to the current scenario, millions of individuals worldwide have dementia. This review provides with an overview of dementia before moving on to its subtypes (neurodegenerative and non-neurodegenerative) and pathophysiology. It also discusses the incidence and severity of dementia, focusing on Alzheimer's disease with its different hypotheses such as Aβ cascade hypothesis, Tau hypothesis, inflammatory hypothesis, cholinergic and oxidative stress hypothesis. Alzheimer's disease is the most common type and a progressive neurodegenerative illness distinct by neuronal loss and resulting cognitive impairment, leading to dementia. Alzheimer's disease (AD) is considered the most familiar neurodegenerative dementias that affect mostly older population. There are still no disease-modifying therapies available for any dementias at this time, but there are various methods for lowering the risk to dementia patients by using suitable diagnostic and evaluation methods. Thereafter, the management and treatment of primary risk elements of dementia are reviewed. Finally, the future perspectives of dementia (AD) focusing on the impact of the new treatment are discussed.

Alzheimer’s disease (AD) is perceived with various pathophysiological characteristics such oxidative stress, senile plaques, neuroinflammation, altered neurotransmission immunological changes, neurodegenerative pathways, and age-linked alterations. A great deal of studies even now are carried out for comprehensive understanding of pathological processes of AD, though many agents are in clinical trials for the treatment of AD. Retinoids and retinoic acid receptors (RARs) are pertinent to such attributes of the disease. Retinoids support the proper functioning of the immunological pathways, and are very potent immunomodulators. The nervous system relies heavily on retinoic acid signaling. The disruption of retinoid signaling relates to several pathogenic mechanisms in the normal brain. Retinoids play critical functions in the neuronal organization, differentiation, and axonal growth in the normal functioning of the brain. Disturbed retinoic acid signaling causes inflammatory responses, mitochondrial impairment, oxidative stress, and neurodegeneration, leading to Alzheimer’s disease (AD) progression. Retinoids interfere with the production and release of neuroinflammatory chemokines and cytokines which are located to be activated in the pathogenesis of AD. Also, stimulating nuclear retinoid receptors reduces amyloid aggregation, lowers neurodegeneration, and thus restricts Alzheimer’s disease progression in preclinical studies. We outlined the physiology of retinoids in this review, focusing on their possible neuroprotective actions, which will aid in elucidating the critical function of such receptors in AD pathogenesis.

Obesity-related metabolic dysfunction, endothelium imbalance, chronic inflammation, immune dysregulation, and its comorbidities may all have a role in systemic inflammation, leading to the pulmonary fibrosis and cytokine storm, which leads to failure of lung function, which is a hallmark of severe SARS-CoV-2 infection. Obesity may also disrupt the function of mucociliary escalators and cooperation of epithelial cell’s motile cilia in the airway, limiting the clearance of the coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2). Adipose tissues in obese patients have a greater number of proteases and receptors for SARS-CoV-2 admittance, proposing that they could serve as an accelerator and reservoir for this virus, boosting immunological response and systemic inflammation. Lastly, anti-inflammatory cytokines such as anti-IL-6 and the infusion of mesenchymal stem cells could be used as a modulation therapy of immunity to help COVID-19 patients. Obesity, on the other hand, is linked to the progress of COVID-19 through a variety of molecular pathways, and obese people are part of the SARS-CoV-2 susceptible individuals, necessitating more protective measures.

Owing to the challenging ethos of global healthcare system, the Alzheimer’s Disease (AD) researchers are consistently striving for a suitable target for disease amelioration. Besides the neurotransmitter release by neurons, the cells release tau proteins and amyloid peptides, within the extracellular vacancies, aggregating into tangles and plaques (AD pathological hallmarks). During neuro-stimulation, release of neuromodulator noradrenaline (NA), contained in the locus coeruleus (LC), exerts a significant impact on the neurons and microglia. The production of amyloid-β (Aβ) and hyperphosphorylation of tau proteins are affected by the α2A and β adrenoreceptors, parallel to influencing their clearance. The manuscript entails a detailed understanding of the LC-NA system, as a possible avenue in AD management. The authors provide a comprehensive data on AD pathology and its link with LC neuroanatomical projections, followed by the pathogenic implications of LC-NA system in AD. The data also integrates numerous studies from online databases, evidently supporting the loss of the system integrity in AD patients, and the impact of the sympathetic system on specific AD hallmarks. Thus, the objective of this review is to compile a wide compendium of studies, for the convenience of the neuro-researchers, aiding in the establishment of a suitable therapeutic regimen for AD treatment.

Quantitative correlations of chemical compounds' biological activity (response variables) with their molecular structures are known as QSARs (independent variables). The molecular descriptors account for a molecule's conformational, constitutional, thermodynamic, steric effects, and electronic characteristics. Molecular docking is one of the most commonly used strategies in structure-based drug design because of its ability to predict the binding-conformation of small-molecule ligands to the proper target binding site. The study of binding behaviour aids in the rational design of therapeutics at the molecular level. A series of novel bioactive oxopyrrolidine derivatives were reported to be synthesized from benzimidazole, pyrrolidinone, pyrrole, 1,2,4-triazole, thiazole, and oxadiazole with 1-(3-(1,3-thiazol-2-yl)phenyl)-5-oxopyrrolidines substituents. Consequently, oxopyrrolidines used possess thiazole ring obtained from reaction of either benzenecarbothioamide, tioureido acid or thiocarbamide with 1-(4-(bromoacetyl)phenyl)-5-oxopyrrolidine-3-carboxylic acid heterocyclic fragments. It was further compared with control Oxytetracycline in which quinoxaline containing fragment showed the more marked effect than of the used control antibiotic. Therefore, this study aimed to build a robust QSAR model to predict the anti-bacterial activity of some oxopyrolidines compounds against Staphylococcus aureus and carry out molecular docking studies between the compounds of the tyrosyltRNAsynthethase receptor. Based on the obtained values of the validation parameters, such as R2 (0.9049), R2adj (0.8789), and Q2cv(0.8365), necessary to evaluate the strength and robustness of the QSAR model, the developed QSAR model was deemed to be statistically significant. Some compounds were chosen and docked with the Staphylococcustyrosyl tRNA synthethase receptor, and the results suggest that C3, C7, C12, C17, C18, and C19 with free binding energies (FBE) −10.0 kcal/mol, −9.6 kcal/mol, −10.2 kcal/mol, −10.1 kcal/mol, −10.6 kcal/mol and −9.7 kcal/mol respectively were better than the standard tyrosyltRNAsynthethase inhibitor (Linezolid, FBE = −8.3 kcal mol−1). Furthermore, these compounds met the drug-likeness criteria and were orally bioavailable. The six compounds' modeling, docking, and drug similarity features broaden the scope of novel derivative design, manufacturing, and testing against Staphylococcus aureus.

Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.

Pyridines and pyrimidines are the class of heterocyclic nitrogenous compounds having plethora of applications in anticancer drug development. These synthetic sources serve as the potent class of compounds in treatment of breast cancer, myeloid leukemia, pancreatic cancer, liver cancer and idiopathic respiratory fibrosis etc. The present review enumerates the results of studies published during past three years (2019–2021) on pyridine and pyrimidine analogues with their respective anticancer properties characterized in vitro or through in silico studies and illustrates their potential in development of anticancer agents. Recent advances on pyridine and pyrimidine analogues mentioned in this review add to the appealing opportunities for cancer therapy.

Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the BTK-kinase domain and its inhibitors from recent three-dimensional structures of inhibitor-bound BTK in the protein data bank (PDB). Additionally, this review analyzes BTK-mediated effector responses of B-cell development and antibody production. Covalent inhibitors contain an α, β-unsaturated carbonyl moiety that forms a covalent bond with Cys481, stabilizing αC-helix in inactive-out conformation which inhibits Tyr551 autophosphorylation. Asn484, located two carbons far from Cys481, influences the stability of the BTK-transition complex. Non-covalent inhibitors engage the BTK-kinase domain through an induced-fit mechanism independent of Cys481 interaction and bind to Tyr551 in the activation kink resulting in H3 cleft, determining BTK selectivity. Covalent and non-covalent binding to the kinase domain of BTK shall induce conformational changes in other domains; therefore, investigating the whole-length BTK conformation is necessary to comprehend BTK’s autophosphorylation inhibition. Knowledge about the structural complementarity of BTK and its inhibitors supports the optimization of existing drugs and the discovery of drugs for implication in B-cell malignancies and autoimmune diseases.

Monoclonal antibodies (mAbs) are a fast-growing class of biopharmaceuticals. They are widely used in the identification and detection of cell makers, serum analytes, and pathogenic agents, and are remarkably used for the cure of autoimmune diseases, infectious diseases, or malignancies. The successful application of therapeutic mAbs is based on their ability to precisely interact with their appropriate target sites. The precision of mAbs rely on the isolation techniques delivering pure, consistent, stable, and safe lots that can be used for analytical, diagnostic, or therapeutic applications. During the creation of a biologic, the key quality features of a particular mAb, such as structure, post-translational modifications, and activities at the biomolecular and cellular levels, must be characterized and profiled in great detail. This implies the requirement of powerful state of the art analytical techniques for quality control and characterization of mAbs. Until now, various analytical techniques have been developed to characterize and quantify the mAbs according to the regulatory guidelines. The present review summarizes the major techniques used for the analyses of mAbs which include chromatographic, electrophoretic, spectroscopic, and electrochemical methods in addition to the modifications in these methods for improving the quality of mAbs. This compilation of major analytical techniques will help students and researchers to have an overview of the methodologies employed by the biopharmaceutical industry for structural characterization of mAbs for eventual release of therapeutics in the drug market.

Despite presence of substantial evidence suggesting the pivotal role of amyloid (Aβ) in Alzheimer's disease (AD), very few therapeutic agents have been able to ameliorate the disease. This paved the way for the discovery of antibody-based immunotherapy to ace Aβ clearance and curb neuronal toxicity, resulting in revival of aducanumab, which following its entry into the brain, interacts with the parenchymal amyloid and decreases Aβ concentration, in a dose-dependent manner. However, the surprising approval from the FDA has created a controversy among healthcare professionals, due to Alzheimer's related imaging abnormality (ARIA) and hypersensitivity, serving as backlogs in its acceptance. Therefore, aducanumab is recognised as being “risen from the grave”, accompanied with contrasting statements within the healthcare paradigm. The manuscript provides a collection of data, aiming to elucidate, both the commendable and critical faces, simultaneously intending to gain the attention of the global researchers towards the possibility of disease-modifying therapy in AD. The manuscript discusses the failure of anti-amyloid therapies in AD, that have accelerated the need to find a suitable therapeutic approach, followed by the discussion of timeline and impact of aducanumab in AD models, alongside the controversial judgement raising significant question. Besides, the authors throw some light on the onco-therapeutic implications of the drug approval, which is identified as a significant consequence of the event. The text provides a holistic picture of the drug action, and enlists the considerations for the future, that might be beneficial to both the acceptance of the drug, and the treatment of the disease.

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets – kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways – on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.

Growing evidence suggests that neuronal dysfunction in the endo-lysosomal and autophagic processes contributes to the onset and progression of neurodegenerative diseases such as Alzheimer's disease (AD). Since they are the primary cellular systems involved in the production and clearance of aggregated amyloid plaques, endo-lysosomal or autophagic equilibrium must be maintained throughout life. As a result, variations in the autophagic and endo-lysosomal torrent, as a measure of degenerative function in these sections or pathways, may have a direct impact on disease-related processes, such as Aß clearance from the brain and interneuronal deposition of Aß and tau aggregates, thus disrupting synaptic plasticity. The discovery of several chromosomal factors for Alzheimer's disease that are clinically linked to regulation of the endocytic pathway, including protein aggregation and removal, supports the theory that the endo-lysosomal/autophagic torrent is more susceptible to impairment, especially as people age, thus catalysing the onset of disease. Although the role of endo-lysosomal/autophagic dysfunction in neurodegeneration has progressed in recent years, the field remains underdeveloped. Because of its possible therapeutic implications in Alzheimer's disease, further study is needed to explain the possibilities for effective autophagy regulation.

Objective: The free and active concentration of drugs and thereby their pharmacokinetic properties are controlled by their binding to human serum albumin (HSA) protein. Irbesartan (IRB), an antihypertensive drug was aimed to be investigated in terms of its binding interactions with different sites of HSA using in silico molecular docking technique along with the commonly employed spectroscopic techniques. Methods: Using FT-IR spectroscopy, the spectral shifting and intensity variations before and after complexation with IRB were studied for amide A, amide-I as well as amide-II of HSA. The absorbance of HSA with and without increasing concentrations of IRB was studied at 280 nm and the binding constant was determined using UV-spectroscopy. Molecular docking study was performed, and the types of interactions were predicted. Results: The IR spectra of IRB-HSA complex showed reductions in the intensities of amide-I and II bands as well as marked reduction in the α-helix content of HSA. The absorbance of HSA protein increased with increasing concentrations of drug. A binding constant value of 5.64 × 104 M−1 was calculated indicating good interaction. Molecular docking studies showed that IRB interacts more effectively with site-I of HSA through greater number of hydrogen bonds and strong π–charge (electrostatic) interactions than with site-II. Conclusions: The spectroscopic and molecular docking techniques proved to be effective tools to study the drug-protein interaction which provided accurate results as evident from these studies. Studying drug-albumin interaction is of utmost importance as it directly influences the overall pharmacokinetics of the drugs including its distribution, metabolism and therefore the duration of action.

Protein misfolding causes aggregation and build-up in a variety of brain diseases. There are numeral molecules that are linked with the protein homeostasis mechanism. Molecular chaperones are one of such molecules that are responsible for protection against protein misfolded and aggregation-induced neurotoxicity. Many studies have explored the participation of molecular chaperones in Parkinson’s disease, Alzheimer’s disease, Amyotrophic lateral sclerosis, and Huntington’s diseases. In this review, we highlighted the constructive role of molecular chaperones in neurological diseases characterized by protein misfolding and aggregation and their capability to control aberrant protein interactions at an early stage thus successfully suppressing pathogenic cascades. A comprehensive understanding of the protein misfolding associated with brain diseases and the molecular basis of involvement of chaperone against aggregation-induced cellular stress might lead to the progress of new therapeutic intrusion-related to protein misfolding and aggregation.

Caralluma retrospiciens (Ehrenb) is a desert plant widely distributed in the hilly semi-desert regions of southern part of Saudi Arabia. The exudate gel (EG) from the stem of plant is occasionally used for wound healing by the people of the southern part of Saudi Arabia. This study investigated the phytochemical composition, FT-IR, GC–MS spectral analysis and in vitro antibacterial activity of the EG from the stem of C. retrospiciens (Ehrenb). The plant C. retrospiciens (Ehrenb.) was collected from the hills of Rijal Almaa, a heritage village of Saudi Arabia. The EG was isolated from the stem of C. retrospiciens (Ehrenb.). Physical parameters such as viscosity and zeta potential (ZP) were determined. Phytochemical analysis, FT-IR and GC–MS spectroscopy analysis were performed to determine the bio active constituents. The antibacterial activity of the isolated gel was performed by in vitro agar well diffusion technique. The study demonstrated that the viscosity and ZP of EG influenced the efficacy of antibacterial spectral properties. The FT-IR spectroscopy of the EG showed various functional groups at 3278.29, 2951.16, 2840.44, 2527.55, 2161.67, 1647.40, 1450.06, 1406.7, 1286, 1108.34, 5536.63 cm−1. Various pharmaceutically important chemical compounds were identified using GC–MS analysis. The bioactive compounds are “Sorbic Acid”, “Rhodopsin”, “1-Heptatriacotanol”, “Oxiraneundecanoic acid, 3-pentyl-, methyl ester, trans”, “Cholestan-3-ol, 2-methylene-, (3á,5à)”, “Benzoic acid”, “3-pentyl-, methyl ester trans”, “Hexanoic acid, 2-ethyl-, oxybis (2,1-ethanediyloxy-2,1-ethanediyl) ester”, etc. The antibacterial effect of the EG showed a wide spectrum of activity against the screened human pathogenic bacteria. The results demonstrate the bioactive principles of EG from C. retrospiciens (Ehrenb.) exerts the antibacterial properties in vitro.

In the present work, ginger essential oil (GEO) loaded chitosan (CS) based films incorporated with varying concentrations of gelatin (GE) were fabricated and dried at different conditions (25 °C and 45 °C). The physio-chemical, mechanical and antioxidant potential of the films were determined. Films dried at 45 °C showed better physical attributes and less thickness, swelling degree (SD), moisture content, water vapor permeability (WVP), more transparency, and better mechanical characteristics. Fourier transform infrared spectroscopy (FTIR) revealed the chemical composition and interaction between the functional groups of the film components. X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) findings revealed that samples dried at 45 °C had more crystalline structure, were thermally stable, and smoother. Antioxidant results showed that films dried at low temperature showed comparatively more (p < 0.0001) antioxidant activity. Additionally, an increase in gelatin concentration improved the tensile strength and swelling factor (p < 0.05), however, had no significant impact on other parameters. The overall results suggested better characteristics of GEO-loaded CS-GE based edible films when dried at 45 °C.

Heart failure (HF) is a serious disorder that affects millions of people worldwide, with a high rate of exercise intolerance, rehospitalization, and death. HF has many underlying causes, including type 2 diabetes mellitus (T2DM), which corresponds with high mortality and short survival among patients with HF. Numerous studies have shown the crucial role of gliflozins, a new generation of blood glucose-lowering medications, in cardiac remodeling, with beneficial impacts on exercise capacity and cardiovascular (CV) mortality, even in non-diabetic individuals. The foundational CV-protective frameworks of these agents are intricate and multifaceted. Dapagliflozin is a new widely used drug and a valuable alternative for patients with T2DM and CV risk factors. Dapagliflozin was approved by the Food and Drug Administration (FDA) in 2019 to lower the risk of HF hospitalization in patients with concurrent T2DM and CV disease or associated risk factors. However, the effects of this new drug on exercise capacity and CV risk still need to be elucidated. The primary objective of this review is to summarize the effect of dapagliflozin on exercise capacity and CV risk in patients with HF.

The drying temperature is one of the crucial parameters that impacts the physical, chemical, and biological properties of edible films (EFs). This parameter determines the degree of crystallinity, which can further impact the film’s mechanical, barrier, and optical properties. The present work is designed to investigate the effect of different drying temperature conditions (25 °C and 45 °C) on ginger essential oil (GEO) loaded Gelatin-sodium alginate composite films over their physical, chemical, and antioxidant properties. Results indicated that drying of films at 25 °C had a positive effect on certain properties of the EFs, such as the moisture content (MC), water solubility (S), swelling degree (SD), water vapor permeability (WVP), and mechanical and optical properties. SEM analysis showed that films dried at 25 °C presented more uniform surface properties with fewer cracks and pores compared to films dried at 45 °C. TGA analysis demonstrated the higher thermal stability of the films when dried at 25 °C. Findings obtained from X-ray diffraction (XRD) and fourier-transform infrared spectroscopy (FTIR) showed film crystallinity and electrostatic interactions between GE, SA, and GEO. Results obtained from antioxidant assays revealed that films dried at 25 °C showed comparable antioxidant capacity to that of butylated hydroxytoluene (BHT). Furthermore, it was found that the addition of SA and GEO to the blank GE films improved their physical, chemical, and antioxidant properties. The present work suggests that GEO loaded GE-SA based films showed better physical, chemical, and antioxidant potential when dried at a lower temperature. These novel materials can be utilized as potential packaging materials in the food industry.

Since ancient times, Chrysopogon zizanioides has been utilized as a traditional medicinal plant for the treatment of numerous ailments, but neither its plant extract form nor its phytoconstituents have been fully explored. With this in mind, the present research was designed to isolate and structurally characterize one of its chemical constituents and evaluate its cytotoxic potential. Therefore, an ethanolic extract of roots was prepared and subjected to column chromatography using solvents of varying polarities. The obtained pure compound was characterized using various chromatographic and spectroscopic techniques such as high-performance liquid chromatography (HPLC), carbon and proton nuclear magnetic resonance (NMR), and liquid chromatography–mass spectroscopy (LC-MS) and identified as longifolene. This compound was evaluated for its cytotoxic potential using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the prostate (DU-145), oral (SCC-29B) cancer cell line and normal kidney cell line (Vero cells), taking doxorubicin as a standard drug. The obtained outcomes revealed that longifolene possesses cytotoxic potential against both prostate (IC50 = 78.64 µg/mL) as well as oral (IC50 = 88.92 µg/mL) cancer cell lines with the least toxicity in healthy Vero cells (IC50 = 246.3 µg/mL) when compared to doxorubicin. Hence, this primary exploratory study of longifolene exhibited its cytotoxic potency along with wide safety margins in healthy cell lines, giving an idea that the compounds possess some ability to differentiate between cancerous cells and healthy cells.

The main characteristic feature of diabetes mellitus is the disturbance of carbohydrate, lipid, and protein metabolism, which results in insulin insufficiency and can also lead to insulin resistance. Both the acute and chronic diabetic cases are increasing at an exponential rate, which is also flagged by the World Health Organization (WHO) and the International Diabetes Federation (IDF). Treatment of diabetes mellitus with synthetic drugs often fails to provide desired results and limits its use to symptomatic treatment only. This has resulted in the exploration of alternative medicine, of which herbal treatment is gaining popularity these days. Owing to their safety benefits, treatment compliance, and ability to exhibit effects without disturbing internal homeostasis, research in the field of herbal and ayurvedic treatments has gained importance. Medicinal phytoconstituents include micronutrients, amino acids, proteins, mucilage, critical oils, triterpenoids, saponins, carotenoids, alkaloids, flavonoids, phenolic acids, tannins, and coumarins, which play a dynamic function in the prevention and treatment of diabetes mellitus. Alkaloids found in medicinal plants represent an intriguing potential for the inception of novel approaches to diabetes mellitus therapies. Thus, this review article highlights detailed information on alkaloidal phytoconstituents, which includes sources and structures of alkaloids along with the associated mechanism involved in the management of diabetes mellitus. From the available literature and data presented, it can be concluded that these compounds hold tremendous potential for use as monotherapies or in combination with current treatments, which can result in the development of better efficacy and safety profiles.

In the current work, we fabricated gelatin–casein-based edible films (GC-EFs) crosslinked with gallic acid (GA). We analyzed the physiochemical characteristics, crystallinity, thermal stability, and surface properties of the EFs using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). It was found that the edible films possessed a semi-crystalline structure. Addition of GA enhanced the thermal stability of the edible films as well as the surface properties of the films. It was found that a higher concentration of GA (4–5% w/v) significantly improved the surface properties, observed in the surface and cross-sectional examination of SEM micrographs. EFs containing higher amounts of GA showed more compact and denser structures with smoother and more homogeneous surfaces than the control samples. In addition, swelling degree (SD), thickness, water solubility (WS), moisture content (MC), and water vapor permeability (WVP) were found to be low in EFs containing more GA concentration. Mechanical parameters revealed that the Young modulus (Ym) and tensile strength (TS) increased with a rise in GA concentration, and elongation at break (EB) reduced with a rise in GA concentration. In transparency and color analysis, it was observed that GA positively affected the transparency of the edible films.

The longstanding progressive neurodegenerative conditions of the central nervous system arise mainly due to deterioration, degradation and eventual neuronal cell loss. As an individual ages, the irreversible neurodegenerative disorders associated with aging also begin to develop, and these have become exceedingly prominent and pose a significant burden mentally, socially and economically on both the individual and their family. These disorders express several symptoms, such as tremors, dystonia, loss of cognitive functions, impairment of motor activity leading to immobility, loss of memory and many more which worsen with time. The treatment employed in management of these debilitating neurodegenerative disorders, such as Parkinson’s disease (which mainly involves the loss of dopaminergic neurons in the nigrostriatal region), Alzheimer’s disease (which arises due to accumulation of Tau proteins causing diffusive atrophy in the brain), Huntington’s disease (which involves damage of striatal and spinal neurons, etc.), have several adverse effects, leading to exploration of several lead targets and molecules existing in herbal drugs. The current review highlights the mechanistic role of natural products in the treatment of several neurodegenerative and cerebrovascular diseases such as Parkinson’s disease, Alzheimer’s disease, ischemic stroke and depression.

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.

Immunotherapy, which stimulates the body’s immune system, has received a considerable amount of press in recent years because of its powerful benefits. Cancer immunotherapy has shown long-term results in patients with advanced disease that are not seen with traditional chemotherapy. Immune checkpoint inhibitors, cytokines like interleukin 2 (IL-2) and interferon-alpha (IFN), and the cancer vaccine sipuleucel-T have all been licensed and approved by the FDA for the treatment of various cancers. These immunotherapy treatments boost anticancer responses by stimulating the immune system. As a result, they have the potential to cause serious, even fatal, inflammatory and immune-related side effects in one or more organs. Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell therapy are two immunotherapy treatments that are increasingly being used to treat cancer. Following their widespread usage in the clinic, a wave of immune-related adverse events (irAEs) impacting virtually every system has raised concerns about their unpredictability and randomness. Despite the fact that the majority of adverse effects are minimal and should be addressed with prudence, the risk of life-threatening complications exists. Although most adverse events are small and should be treated with caution, the risk of life-threatening toxicities should not be underestimated, especially given the subtle and unusual indications that make early detection even more difficult. Treatment for these issues is difficult and necessitates a multidisciplinary approach involving not only oncologists but also other internal medicine doctors to guarantee quick diagnosis and treatment. This study’s purpose is to give a fundamental overview of immunotherapy and cancer-related side effect management strategies.

In the original publication [...]

This study was aimed to perform the mechanistic investigations of chalcone scaffold as inhibitors of acetylcholinesterase (AChE) enzyme using molecular docking and molecular dynamics simulation tools. Basic chalcones (C1–C5) were synthesized and their in vitro AChE inhibition was tested. Binding interactions were studied using AutoDock and Surflex-Dock programs, whereas the molecular dynamics simulation studies were performed to check the stability of the ligand–protein complex. Good AChE inhibition (IC50 = 22 ± 2.8 to 37.6 ± 0.75 μM) in correlation with the in silico results (binding energies = −8.55 to −8.14 Kcal/mol) were obtained. The mechanistic studies showed that all of the functionalities present in the chalcone scaffold were involved in binding with the amino acid residues at the binding site through hydrogen bonding, π–π, π–cation, π–sigma, and hydrophobic interactions. Molecular dynamics simulation studies showed the formation of stable complex between the AChE enzyme and C4 ligand.

Over the last 25 years, the human endocannabinoid system (ECS) has come into the limelight as an imperative neuro-modulatory system. It is mainly comprised of endogenous cannabinoid (endocannabinoid), cannabinoid receptors and the associated enzymes accountable for its synthesis and deterioration. The ECS plays a proven role in the management of several neurological, cardiovascular, immunological, and other relevant chronic conditions. Endocannabinoid or endogenous cannabinoid are endogenous lipid molecules which connect with cannabinoid receptors and impose a fashionable impact on the behavior and physiological processes of the individual. Arachidonoyl ethanolamide or Anandamide and 2-arachidonoyl glycerol or 2-AG were the endocannabinoid molecules that were first characterized and discovered. The presence of lipid membranes in the precursor molecules is the characteristic feature of endocannabinoids. The endocannabinoids are released upon rapid enzymatic reactions into the extracellular space via activation through G-protein coupled receptors, which is contradictory to other neurotransmitter that are synthesized beforehand, and stock up into the synaptic vesicles. The current review highlights the functioning, synthesis, and degradation of endocannabinoid, and explains its functioning in biological systems.