A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality.

The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression.

Background: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (A. laxiflora) has been indicated in traditional medicine to treat depression. However, scientific rationalization is still lacking. Hence, this study aimed to investigate the antidepressant potential of A. laxiflora using network pharmacology and molecular docking analysis. Materials and methods: The active compounds and potential targets of A. laxiflora and depression-related targets were retrieved from public databases, such as PubMed, PubChem, DisGeNET, GeneCards, OMIM, SwissTargetprediction, BindingDB, STRING, and DAVID. Essential bioactive compounds, potential targets, and signaling pathways were predicted using in silico analysis, including BA-TAR, PPI, BA-TAR-PATH network construction, and GO and KEGG pathway enrichment analysis. Later on, with molecular docking analysis, the interaction of essential bioactive compounds of A. laxiflora and predicted core targets of depression were verified. Results: The network pharmacology approach identified 15 active compounds, a total of 219 compound-related targets, and 14,574 depression-related targets with 200 intersecting targets between them. SRC, EGFR, PIK3R1, AKT1, and MAPK1 were the core targets, whereas 3-acetyloleanolic acid and 3-acetylursolic acid were the most active compounds of A. laxiflora with anti-depressant potential. GO functional enrichment analysis revealed 129 GO terms, including 82 biological processes, 14 cellular components, and 34 molecular function terms. KEGG pathway enrichment analysis yielded significantly enriched 108 signaling pathways. Out of them, PI3K-Akt and MAPK signaling pathways might have a key role in treating depression. Molecular docking analysis results exhibited that core targets of depression, such as SRC, EGFR, PIK3R1, AKT1, and MAPK1, bind stably with the analyzed bioactive compounds of A. laxiflora. Conclusion: The present study elucidates the bioactive compounds, potential targets, and pertinent mechanism of action of A. laxiflora in treating depression. A. laxiflora might exert an antidepressant effect by regulating PI3K-Akt and MAPK signaling pathways. However, further investigations are required to validate.

Evaluation of chalcones as new glycogen phosphorylase inhibitors - an in-vitro and in-silico approach.

Diabetes mellitus (DM) remains one of the pivotal diseases that have drawn the attention of researchers recently and during the last few decades. Due to its devastating symptoms, attempts to develop new drugs with mild side effects have resulted in a number of drugs that are functioning through various mechanisms. Among these, Glycogen phosphorylase (GP) inhibitors emerged as a new strategy for combating DM. GP is an enzyme that regulates blood glucose levels; it catalyses the breakdown of glycogen to glucose-1-phosphate in the liver and tissues with high and fluctuating energy demands. In the present research, we evaluate the possibility of type 2 diabetes therapy with the help of chalcones which are known to have antidiabetic activities. For this purpose, 29 chalcones were modelled, synthesised and investigated for their inhibitory activity against GP using in-vitro methods. Compounds 1, 2, and 3 were found to be the most potent compounds with IC50 values 26.6, 57.1 and 75.6 µM respectively. The observed results were further validated using in-silico methods. Molecular docking simulation revealed interaction patterns that explain the structure-activity relationships of the compounds with GP. Molecular dynamic (MD) simulation demonstrated a stable complex formation between compound 1 and GP through lower value and uniformity in root mean square deviation (RMSD) of the complex and root mean square fluctuation (RMSF) of the protein Cα.

Polymorphism of HLA and Susceptibility of Breast Cancer.

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.

Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration.

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.

Exploring LIPIDs for their potential to improves bioavailability of lipophilic drugs candidates: A review.

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.

Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene-2,4-thiazolidinediones as partial PPAR-γ agonists.

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 < 0.05 to p < 0.0001) among the diabetic control and standard drug rosiglitazone groups. In molecular docking study, compounds 5c and 5d exhibited higher binding energies (- 10.1 and - 10.0 kcal/mol, respectively) than the native ligand, non-thiazolidinedione PPAR-γ partial agonist (nTZDpa) (- 9.8 kcal/mol). MD simulation further authenticated the stability of compound 5c-PPAR-γ complex over the 150 ns duration. The RMSD, RMSF, rGyr, SASA, and binding interactions of compound 5c-PPAR-γ complex were comparable to those of native ligand nTZDpa-PPAR-γ complex, suggesting that the title compounds have the potential to be developed as partial PPAR-γ agonists.

Daidzein from Dietary Supplement to a Drug Candidate: An Evaluation of Potential.

Daidzein (DDZ) is a well-known nutraceutical supplement belonging to the class of isoflavones. It is isolated from various sources such as alfalfa, soybean, and red clover. It demonstrates a broad array of pharmacological/beneficial properties such as cardiovascular exercise, cholesterol reduction, and anticancer, antifibrotic, and antidiabetic effects, which make it effective in treating a wide range of diseases. Its structure and operation are the same as those of human estrogens, which are important in preventing osteoporosis, cancer, and postmenopausal diseases. It is thus a promising candidate for development as a phytopharmaceutical. Addressing safety, efficacy, and physicochemical properties are the primary prerequisites. DDZ is already ingested every day in varying amounts, so there should not be a significant safety risk; however, each indication requires a different dose to be determined. Some clinical trials are already being conducted globally to confirm its safety, efficacy, and therapeutic potential. Furthermore, as a result of its therapeutic influence on health, in order to establish intellectual property, patents are utilized. In light of the vast potential of eugenol, this review presents a detailed data collection on DDZ to substantiate the claim to develop it in the therapeutic category.

Design, optimization, and characterization of Althaea officinalis-loaded transliposomes for the treatment of atopic dermatitis: a Box Behnken Design, in vitro, and ex vivo study.

A chronic skin disorder called atopic dermatitis (AD) is brought on by the deterioration of the skin's barrier function marked by inflammation, dryness, and bacterial infection along with immunological changes. Althaea officinalis (AO), known for its anti-inflammatory and immunomodulatory properties, has been explored as a potential treatment for AD. This study aimed to develop and evaluate a novel transliposomes (TL) formulation containing AO for AD treatment. Using rotary evaporation, AO-TL formulations were created and optimized employing Box Behnken Design. The optimized AO-TL formulation showed consistent characteristics: vesicle size of 145.8 nm, polydispersity index of 0.201, zeta potential of -28.22 mV, and entrapment efficiency of 86.21%. TEM imaging shows the spherical shapes of the vesicle. These findings demonstrate the formulation's stability and ability to encapsulate AO effectively. In vitro drug release studies revealed that the AO-TL formulation released 81.28% of the drug, outperforming conventional AO dispersion (56.80%). Additionally, when applied to rat skin, the TL gel demonstrated deeper penetration (30 µm) in comparison to the standard solution (5.0 µm) based on confocal laser scanning microscopy (CLSM). Ex vivo and dermatokinetics studies showed improved penetration of drug-loaded transliposomes gel in rat skin than the conventional AO gel. Overall, the optimized AO-TL formulation offers promising characteristics and performance for the topical treatment of AD. Its drug release, antioxidant activity, and deeper penetration suggest enhanced therapeutic effects. Further research and clinical trials are needed to validate its efficacy and safety in AD patients.

Anticancer clinical efficiency and stochastic mechanisms of belinostat.

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.

Analytical Techniques for the Characterization and Quantification of Monoclonal Antibodies.

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.

Understanding the Molecular Aspects of Vitamins in Parkinson's Disease: Present-day Concepts and Perspectives.

Parkinson's disease (PD) is designated as a convoluted nerve cell devastating disorder that encompasses the profound declination of dopaminergic (DArgic) nerve cells of the mesencephalon region. The condition is sketched by four eminent motor manifestations, namely, slow movement, muscle tension, shaking, and disrupted balance, but the pathology behind these manifestations is still vague. Modern-day medicinal treatment emphasizes curbing the manifestations via introducing a gold standard (levodopa) instead of forestalling the DArgic nerve cell destruction. Therefore, the invention and utilization of novel neuroprotective candidates are of paramount importance in overcoming PD. Vitamins are organic molecules engaged in the modulation of evolution, procreation, biotransformation, and other operations of the body. Numerous studies employing varying experimental models have promulgated a prominent linkage between vitamins and PD. Vitamins, owing to their antioxidant and gene expression modulation abilities, might be efficacious in PD therapy. Recent corroborations depict that adequate augmentation of vitamins might de-escalate the manifestations and emergence of PD; however, the safety of daily vitamin intake must be considered. By assembling the comprehensive information obtained from existing publications via searching various renowned medical portals, the investigators render in-depth insights into the physiological association amongst vitamins (D, E, B3, and C) and PD and concerned pathological processes and their safeguarding actions in varied PD models. Furthermore, the manuscript delineates the remedial aptitude of vitamins in PD therapy. Conclusively, augmentation of vitamins (owing to their antioxidant and gene expression regulation capabilities) might appear as a novel and terribly efficacious ancillary therapeutic approach for PD.

Virosome: An engineered virus for vaccine delivery.

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.

Targeting multifunctional magnetic nanowires for drug delivery in cancer cell death: an emerging paradigm.

Apoptosis, often known as programmed cell death is a mechanism used by numerous species to maintain tissue homeostasis. The process leading to cell death is complicated because it requires the stimulation of caspases. According to several studies, nanowires have important medical benefits, can kill cells by adhering to cancer cells, destroying them, and killing the entire cell using a triple attack that integrates vibration, heat, and drug delivery to trigger apoptosis. The sewage effluents and industrial, fertilizer and organic wastes decomposition can produce elevated levels of chemicals in the environment which may interrupt the cell cycle and activate apoptosis. The purpose of this review is to give a thorough summary of the evidence that is currently available on apoptosis. Current review discussed topics like the morphological and biochemical alterations that occur during apoptosis, as well as the various mechanisms that cause cell death, including the intrinsic (or mitochondrial), extrinsic (or death receptor), and intrinsic endoplasmic reticulum pathway. The apoptosis reduction in cancer development is mediated by (i) an imbalance between pro- and anti-apoptotic proteins, such as members of the B-cell lymphoma-2 (BCL2) family of proteins, tumour protein 53 and inhibitor of apoptosis proteins, (ii) a reduction in caspase activity, and (iii) impaired death receptor signalling. This review does an excellent task of outlining the function of nanowires in both apoptosis induction and targeted drug delivery for cancer cells. A comprehensive summary of the relevance of nanowires synthesised for the purpose of inducing apoptosis in cancer cells has been compiled collectively.

Structural Complementarity of Bruton's Tyrosine Kinase and Its Inhibitors for Implication in B-Cell Malignancies and Autoimmune Diseases.

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, ß-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.

Quantification of Luteolin, Apigenin and Chrysoeriol in Tecoma stans by RP-HPLC Method.

Tecoma stans (Fam. Bignoniaceae) is also popularly known as yellow bells and yellow trumpet bush in vernacular terminology. Limited and variable data are available from the literature regarding the quantification of luteolin, apigenin and chrysoeriol, which are considered as the most active pharmacological active constituents. High-performance liquid chromatography-photodiode array detection has been developed for the determination of the bioactive flavonoids, luteolin, apigenin and chrysoeriol, from the methanolic extract of the leaves of T. stans. A column packed with a pentafluorophenyl-based stationary phase was used for the separation of the analytes under gradient elution. The detection wavelength was 345 nm. The validation of the method as per the International Council on Harmonisation (ICH) guidelines (ICH 2005) for linearity, accuracy and precision was investigated and found within limits specified by the ICH guidelines. The method was linear over with a good regression coefficient of more than 0.99. The limit of detection of the method was 0.68, 2.97 and 1.76 µg/mL for luteolin, apigenin and chrysoeriol, respectively. In conclusion, a reliable and reproducible method was devised that can be used for the estimation of the said components from T. stans.

The Current Landscape of Bioactive Molecules against DENV: A Systematic Review.

With a 30-fold increase in incidence over the previous 50 years, dengue fever is now the most widespread viral disease transmitted by mosquitoes in the world. The intricate interaction of the human defense system, hereditary predisposition, and specific bitterness elements is more likely to be the pathogenesis of dengue. There are presently no viable treatments for dengue. Synthetic drugs which are used against this ailment also show major side effects. There must be a deeper understanding of the underlying mechanism generating severe symptoms to develop auguring markers, cutting-edge diagnostics, and treatments and finally a well-rounded and secure antiserum. Hence, the aim is to search for safer and more potent drugs derived from plants. Plants or herbs are mainly targeting replication or its enzyme or specific stereotypes, though an exact mechanism of phytoconstituents interfering with the viral replication is still undiscovered. The present attempt provided the update with the objective to bringing up forward pathophysiological eventualities involved in dengue virus along with the naturally derived treatment relevant to provide the impregnable therapy by evading the noxious symptoms for dengue fever. Governor's plum, Cryptocarya chartacea, magnolia berry, and Chinese ginger are such plants exhibiting many effective phytoconstituents against DENV and can be further explored for novel drug discovery by medicinal scientists.

Heavy Metal Contamination in Leafy Vegetables Grown in Jazan Region of Saudi Arabia: Assessment of Possible Human Health Hazards.

The food chain, through vegetable consumption, is considered to be an important route of heavy metal exposure. Therefore, in this study, heavy metal concentrations in leafy vegetables grown in the Jazan region of Saudi Arabia were assessed using an ICP-MS. Lettuce, radish, mint, parsley and jarjir (Arugula) were selected for study and subjected to digestion using HCl. The results indicated that the Fe level was highest in all vegetables, while jarjir was the most contaminated vegetable. However, no tested metal exceeded the maximum permissible limits set by the FAO/WHO and European Committee. The possible health hazards associated with the exposure to metal contaminants via vegetable consumption were evaluated by estimating target hazard quotient (THQ) values, and the results revealed that the vegetables grown in close proximity of Jazan city were the most contaminated and those in Darb the least. However, the daily intakes of all the tested metals were well below the corresponding oral reference doses (RfDs), and the THQ values were less than unity, suggesting that the vegetables grown in the studied region were safe and the heavy metal exposure via vegetable consumption was unlikely to cause adverse effects to the local inhabitants of the region.

Combined Effect of Drying Temperature and Varied Gelatin Concentration on Physicochemical and Antioxidant Properties of Ginger Oil Incorporated Chitosan Based Edible Films.

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.

Therapeutic Molecular Insights into the Active Engagement of Cannabinoids in the Therapy of Parkinson's Disease: A Novel and Futuristic Approach.

Parkinson's disease is a neurodegenerative disorder which is characterised mostly by loss of dopaminergic nerve cells throughout the nigral area mainly as a consequence of oxidative stress. Muscle stiffness, disorganised bodily responses, disturbed sleep, weariness, amnesia, and voice impairment are all symptoms of dopaminergic neuron degeneration and existing symptomatic treatments are important to arrest additional neuronal death. Some cannabinoids have recently been demonstrated as robust antioxidants that might protect the nerve cells from degeneration even when cannabinoid receptors are not triggered. Cannabinoids are likely to have property to slow or presumably cease the steady deterioration of the brain's dopaminergic systems, a condition for which there is now no treatment. The use of cannabinoids in combination with currently available drugs has the potential to introduce a radically new paradigm for treatment of Parkinson's disease, making it immensely useful in the treatment of such a debilitating illness.