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Since their discovery nearly 30 years ago, fibroblast growth factor homologous factors (FHFs) are now known to control the functionality of excitable tissues through a range of mechanisms. Nervous and cardiac system dysfunctions are caused by loss‐ or gain‐of‐function mutations in FHF genes. The best understood 'canonical' targets for FHF action are voltage‐gated sodium channels, and recent studies have expanded the repertoire of ways that FHFs modulate sodium channel gating. Additional 'non‐canonical' functions of FHFs in excitable and non‐excitable cells, including cancer cells, have been reported over the past dozen years. This review summarizes and evaluates reported canonical and non‐canonical FHF functions. [ABSTRACT FROM AUTHOR]

This article provides a list of references to scientific articles on various topics related to personalized and precision medicine. The references cover subjects such as cardiovascular risk assessment, biomarkers for cancer, machine learning in healthcare, circadian rhythms, and personalized medicine. These articles can serve as a valuable resource for library patrons conducting research on these specific topics. [Extracted from the article]

Genipin polymers are self-forming tensile-load-carrying oligomers, derived from the gardenia fruit, that covalently bond to amines on collagen. The potential therapeutic mechanical benefits of a non-discrete in situ forming mesh of genipin oligomers for degraded spinal discs were first conceived in 1998. Over more than two decades, numerous studies have demonstrated the immediate mechanical effects of this injectable, intra-annular polymeric mesh including an early demonstration of an effect on clinical outcomes for chronic or recurrent discogenic low back pain. This literature review focused on articles investigating mechanical effects in cadaveric animal and human spinal discs, biochemical mechanism of action studies, articles describing the role of mechanical degradation in the pathogenesis of degenerative disc disease, initial clinical outcomes and articles describing current discogenic low back pain treatment algorithms. On the basis of these results, clinical indications that align with the capabilities of this novel injectable polymer-based treatment strategy are discussed. It is intended that this review of a novel nano-scale material-based solution for mechanical deficiencies in biologically limited tissues may provide a helpful example for other innovations in spinal diseases and similarly challenging musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

Combination therapy is a promising approach to address the challenge of antimicrobial resistance, and computational models have been proposed for predicting drug–drug interactions. Most existing models rely on drug similarity measures based on characteristics such as chemical structure and the mechanism of action. In this study, we focus on the network structure itself and propose a drug similarity measure based on drug–drug interaction networks. We explore the potential applications of this measure by combining it with unsupervised learning and semi‐supervised learning approaches. In unsupervised learning, drugs can be grouped based on their interactions, leading to almost monochromatic group–group interactions. In addition, drugs within the same group tend to have similar mechanisms of action (MoA). In semi‐supervised learning, the similarity measure can be utilized to construct affinity matrices, enabling the prediction of unknown drug–drug interactions. Our method exceeds existing approaches in terms of performance. Overall, our experiments demonstrate the effectiveness and practicability of the proposed similarity measure. On the one hand, when combined with clustering algorithms, it can be used for functional annotation of compounds with unknown MoA. On the other hand, when combined with semi‐supervised graph learning, it enables the prediction of unknown drug–drug interactions. [ABSTRACT FROM AUTHOR]

The latest study published in Nature by Andrew R. Burns, Peter J. Roy and co-authors is highlighted in this paper, they investigated a series of novel nematicidal compounds, including Selectivin-A and Selectivin-E, and explored their mechanism of action. Experiments have displayed that the Selectivin compound is inactive to human cells, fish, fungi, insects and even beneficial nematodes. In the exploration of its mechanism of action, it was found that the mechanism of action of Selectivin is different with those of commercial nematocides: Selectivin needs to be activated by biotin produced by nematodes, after that they can be transformed into compounds with high nematicidal activity. This proves that the family of Selectivin compounds has the advantages of high selectivity and environmental friendliness, and their mechanism of action is completely new, proposing a completely new path for the development of new nematicides. [ABSTRACT FROM AUTHOR]

This document is an editorial from the International Journal of Molecular Sciences titled "Recent Advances on Fluorine Chemistry." The purpose of the document is to showcase the latest findings in fluorine chemistry. It discusses the unique properties of fluorine and how they affect the reactivity of molecules. The document also explores various aspects of lanthanide fluoride research, the development of innovative fluorination methods, and the selective addition of fluorine to multiple bonds. Additionally, it highlights the promising areas of aminofluorination reactions, classical methods of functionalization and heterocyclization, and the field of fluoroalkylation. The document concludes by mentioning the use of biocatalysis in fluorination reactions and the formation of the tetrafluoroisopropyl group. [Extracted from the article]

Despite introduction of various novel therapies, treatment options for metastatic castrate resistant prostate cancer (mCRPC) remain limited. This is a retrospective, multi-institution study of 43 patients with mCRPC treated with oral metronomic cyclophosphamide (mCyc), which showed promising, rapid, durable activity and a tolerable toxicity profile in a heavily-pretreated mCRPC population with aggressive clinical, pathologic, and genomic disease features. Introduction: Despite the introduction of various novel therapies for management of metastatic castrate resistant prostate cancer (mCRPC) in recent decades, available treatment options are finite and remain limited. Multiple historical studies have demonstrated activity and a favorable toxicity profile of oral metronomic cyclophosphamide (mCyc) in prostate cancer (PCa). Unlike the cytotoxic immunosuppressive effects of high-dose intravenously-administered cyclophosphamide, continuous low doses of oral mCyc have a unique immune-stimulatory mechanism of action. Materials and Methods: This is a retrospective, multi-institution study of men with 43 patients with mCRPC treated mCyc. Patient demographic information as well as clinical, pathologic, and genomic characteristics of their PCa were extracted. The primary endpoint was the rate of PSA decline by = 50% (ie, PSA50). Additional efficacy and toxicity data as well as cost analysis compared to other commonly used agents in mCRPC was obtained. Results: PSA50 was noted in 20.9% of patients, while an additional 25.6% patients achieved < PSA50 and 6.9% reported improvement in prostate cancer-related symptoms without any PSA reduction. Meanwhile, 9.3% of patients required mCyc dose reduction, 11.6% needed dose interruption due to toxicity, and no treatment discontinuations due to toxicity were observed. mCyc was also cost effective compared to other agents commonly used in mCRPC. Conclusions: Despite the small sample size and retrospective nature of this dataset, mCyc demonstrated promising rapid activity and a tolerable toxicity profile in a heavily pretreated mCRPC population with aggressive clinical, pathologic, and genomic disease features. [ABSTRACT FROM AUTHOR]

This review explores the potential of Indole-3-Carbinol (I3C) and 3,3-Diindolylmethane (DIM) as promising therapeutic agents for leukemia treatment and cancer chemoprevention. The biochemistry and mechanisms of action of I3C and DIM are examined, including their structures, properties, metabolism pathways, and molecular targets relevant to leukemia and cancer prevention. Preclinical studies investigating the effects of I3C and DIM on leukemia cell lines and animal models are summarized, highlighting key findings and implications for clinical translation. Additionally, clinical trials evaluating the safety, pharmacokinetics, and efficacy of I3C and DIM in leukemia treatment and cancer prevention are reviewed, along with ongoing and future clinical trials. Adverse effects, safety considerations and strategies for mitigating risks associated with I3C and DIM supplementation are discussed. Finally, future directions, challenges and unresolved questions in the field of I3C and DIM-based leukemia therapy and cancer chemoprevention are addressed, including potential synergies with existing treatments, exploration of combination therapies and areas for further research. [ABSTRACT FROM AUTHOR]

Although true allergic drug hypersensitivies are rare, adverse reactions to drugs are common and affects the entire population, regardless of age. Often unexplored, it involves significant morbidity, which could be avoided by carrying out a pharmacovigilance investigation and an allergological work-up. Clinical symptoms of drug hypersensitivity depend on the time to the first symptoms after exposure to the drug and the different immune or pharmacological responses involved. The management of the reaction and the allergological assessment depends on these physiopathological mechanisms and the severity of the reaction. [ABSTRACT FROM AUTHOR]

Pollen allelopathy positively or negatively influences the fertilization of plants and has great significance from ecological perspectives. The release of allelochemicals from foreign pollen grains on the stigmatic surface obstructs the processes of fertilisation, seed establishment, tube formation, stigma receptivity, and pollen germination. So far, pollen allelopathy has received little attention and still a growing topic of ecological studies. Therefore, a literature review was undertaken to provide the valuable information regarding the ecological and reproductive implications of pollen allelopathy, heterospecific pollen transfer mechanisms of allelopathic anemophilous and entomophilous plants, and to shed light on the biochemistry and mode of action of allelochemicals. The majority of entomophilous plants share pollinators within communities, and heterospecific pollen transfer by both anemophilous and entomophilous plants causes a reduction in their reproductive success, like pollen germination, tube development, ovule maturation and seed set. For detailed study of pollen allelopathy, a few factors should be considered like metrological parameters, distance travelled by pollen, pollen viability, and stigma receptivity during foreign pollen deposition. A thorough understanding of the biochemical and enzymatic processes that occur after foreign pollen is deposited on the native stigma will open up new perspectives on plant reproduction. Pollen allelochemicals, which have important significance as biocontrol agents for the maintenance of agroecosystems, need to be identified and characterised. The ecological aspects of pollen allelopathy may be well understood with the help of field studies. [ABSTRACT FROM AUTHOR]

Vitex doniana produces a commonly consumed fruit in many places where the tree grows. This wild fruit could contribute to nutrition and food security. Therefore, nutrients and phyto constituents of aqueous extract of the fruit were investigated to evaluate its benefit to consumers. Samples of the fruits were collected from Navrongo in the Upper East Region of Ghana for laboratory analyses. Calcium, potassium, phosphorus, magnesium, sodium, zinc and manganese, as well as vitamins A, C, and Beta carotene; crude fat, carbohydrates, proteins, fibre, ash, and energy contents were determined in the pulp. Oven determination of moisture content, and Atomic Absorption Spectroscopy determination of minerals were carried out. The other parameters were analysed using other appropriate standard methods. The study found that the fruit pulp contains flavonoids, phenols, alkaloids, terpenoids and saponins, as well as vitamins A, C, and ß-carotene. The proximate compositions were 19.045% of moisture, 31.597% fat, 4.056% crude fiber, 0.698% crude protein, 4.234% ash, 36.610% carbohydrate, with a total energy of 448.283 kcal/100g. The pulp also had high levels of potassium (1422 mg/100g), calcium (350 mg/100g), magnesium (132 mg/100g) among others, and also trace levels of manganese (0.943 mg/100g), zinc (2.770 mg/100g). Copper was undetected. The fruit pulp of Vitex doniana has vital nutrients and vitamins that can complement other sources of nutrients, and contribute to food security and good health. It has potential for making valuable commercial juice. Comprehensive studies of wild fruits are recommended to generate policy on the fruits. [ABSTRACT FROM AUTHOR]

Nitrogen‐containing drugs represent one of the worldwide most extensive sources of treatments for different diseases. Indomethacin as example, is one of the most important non‐steroidal anti‐inflammatories (NSAID) indol‐containing drug. Its relevance has been demonstrated the last 50 years with excellent pharmacological results. Its efficacy as an anti‐inflammatory treatment, inspired us the exploration of indol‐containing structurally less elaborated compounds which kept and/or improve the anti‐inflammatory activity compared with indomethacin. Herein is summarized and discussed our initial findings on the synthesis and anti‐inflammatory effect of different 2,3‐diarylindoles, designed for strategically favoring the plausible and selective interactions with COX‐2, on route to new simple NSAID scaffolds. The TPA model and formalin test were used in this study to generate inflammation in mice for conducting the assays with the synthesized 2,3‐diarylindoles. Docking analysis revealed stronger N−H indolic interactions with COX‐2 for 6‐methoxy‐2‐phenyl‐3‐(4‐chlorophenyl)‐1H‐indole, one of the most active of the synthesized compounds when compared with indomethacin. This, experimentally match with the anti‐inflammatory observed effect and putatively indicates the biochemical action mechanism. [ABSTRACT FROM AUTHOR]

Inositol, a group of naturally occurring sugar alcohols, has gained attention for the diverse physiological roles and therapeutic potential. This comprehensive overview examines the administration, efficacy, and potential applications of inositol in various medical contexts. Myo-inositol and D-chiro inositol are the two types of inositol covered in this review, exploring their mechanisms of action and biochemical pathways. Discussions on the administration methods, including supplements and dietary sources, provide insights into optimizing therapeutic outcomes. The review also explores the available data on the effectiveness of inositol in treating diseases like mental health disorders, metabolic disorders, and polycystic ovarian syndrome (PCOS). Furthermore, potential reproductive medicine, neurology, and other areas of applications are explored. This overview provides a comprehensive snapshot of the evolving landscape of inositol research, emphasizing its promising role in various therapeutic interventions and prompting further exploration of its multifaceted benefits. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) was originally described as a small volume of plasma that contains higher concentrations of platelets, compared to peripheral blood. Although currently the use of PRP in most indications is off-label, it is not prohibited. Initially, PRP was used for wound healing and tissue regeneration in fields such as orthopaedics, dermatology, maxillofacial surgery and dentistry. Aim of the study: The aim of this article was to present and summarise the modern production methods, the mechanism of action at the molecular and biochemical level and the most important uses and indications of PRP in present-day medicine. Material and methods: A cross-sectional search of relevant literature was performed in databases using accepted wording. Publications from 2003-2023 were included. The entire process has been supplemented with additional procedures to increase the reliability of this publication. Results: Orthopaedics has gained many minimally invasive therapeutic solutions thanks to PRP. Its effects on ligament and tendon tissues have been studied, where promising data have been proven. Also in aesthetic medicine and dermatology, many treatment strategies have been developed using PRP, mainly for the treatment of acne, androgenic alopecia and delaying tissue ageing as much as possible. Conclusion: Platelet-rich plasma has found application in the treatment of many conditions in orthopaedics, dermatology, aesthetic medicine and dentistry. It is characterised by good therapeutic efficacy, with relatively low risk. However, high-quality studies are still lacking to provide more reliable data. [ABSTRACT FROM AUTHOR]

The underlying mechanisms and biochemical actions responsible for inactivation of pathogenic gram-positive Staphylococcus aureus (S. aureus) and gram-negative Salmonella abony (S. abony) bacteria upon exposure to sub-atmospheric plasma has been investigated. Reduction in colony forming units of the bacteria is established in 60 min and 40 min for S. aureus and S. abony respectively via 6-log reduction curves. The percentage change in reactive oxygen species, such as •OH and H2O2 formed on bacterial membrane during plasma exposure are analysed using spectroflurometer. S. aureus exhibited a significant increase of 324.23% and 1554.84% in •OH and H2O2 radicals respectively. Whereas, 98.14% and 54.49% increase in •OH and H2O2 radicals respectively was observed in S. abony. The oxidation and degradation of DNA is analysed using an ultra violet visible spectrophotometer. The leakage of proteins, lipids, and nucleic acid molecules due to plasma exposure is studied by Attenuated Total Reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). The alteration of secondary protein structure on the cell membrane is observed using Circular Dichroism. Upon exposure to plasma, S. aureus shows a secondary protein structural transition from α-helix (2.4%), β-sheet (78.3%) mixture to modified β-sheet structure (0% α-helix, 79.1% β-sheet). Whereas, S.abony shows a transition from α-helix (1%), β-sheet (64.9%) mixture to modified β-sheet structure (0% α-helix, 74.5% β-sheet). The bacterial morphological study (swelling/shrinking) done using Field Emission Scanning Electron Microscopy (FE-SEM) reveals the deformation of cell membrane. Above findings pave the way for a better understanding of the processes of antimicrobial inactivation strategies when the plasma sterilization process is employed. [ABSTRACT FROM AUTHOR]

The study reports the biochemical characterization and mechanism of action of a novel 19.6 kDa protease inhibitor (PIs) isolated from the seeds of Caesalpinia decapetala belonging to the Fabaceae family. A systematic study was performed to ascertain the purity, specificity, biochemical and structural characterization, and its potential in curbing inflammation in vitro conditions. A two‐step chromatography technique was used to purify the PIs. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and matrix‐assisted laser desorption ionization time of flight were employed to detect the molecular mass of the protein. N‐terminal sequence analysis of the inhibitor showed sequence similarity with the Kunitz family PIs. The in vitro test tube assay was performed for determining the anti‐inflammatory activity and the inhibitor is antiproliferative against macrophage (RAW264.7) and lung cancer cell lines (A549). An effective decrease in the release of inflammatory mediators (NO, IL‐6, TNF‐α) and on the activity of elastase was observed in macrophage cell lines (RAW264.7) which were treated with PIs. The purified inhibitor shows promising results against inflammation. Significance statement: Protease and antiprotease imbalance have an impact on several biological systems which are reported to cause emphysema, thrombosis, clotting disorders, and cancer. Our findings clearly reveal that purified preatease inhibitor, CdTI have significant action as an anti‐proinflammatory and antiproliferative action on lung cancer cells. These findings could lead to protease inhibitors (PIs) being classified as therapeutic potential due to antiproliferative activity on cancer cell lines. These studies provide evidence about the therapeutic potential of serine PIs in inhibiting or regulating the activity of serine proteases secreted by neutrophils. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the protective potential of a pharmaceutically formulated capsule of artichoke leaf powder (ArLP) against aflatoxin B1 (AFB1)-induced hepatotoxicity in male albino rats. In the 42-day experiment, rats were divided into five equal groups: (i) control, treated with sterile water, (ii) treated with 4% DMSO as AFB1 vehicle, (iii) ArLP of 100 mg kg–1 bw, (iv) AFB1 of 72 µg kg–1 bw, and (v) AFB1 plus ArLP. Exposure of rats to AFB1 resulted in hepatotoxicity as manifested by the intensification of oxidative stress, production of free radicals and significant increase in the activity levels of liver function enzymes relative to the control. Significant reductions in both the enzymatic and non-enzymatic antioxidant markers as well as histopathological abnormalities in liver tissues were also observed. Notably, the combined administration of ArLP with AFB1 clearly reduced AFB1-mediated adverse effects leading to the normalization of most of these parameters back to control levels. These findings clearly highlight the potential benefits of artichoke dietary supplements as a safe and natural solution in counteracting the adverse hepatotoxic effects conferred by AFB1 exposure. Further research is warranted to fully dissect the biochemical and molecular mechanism of action of the observed artichoke-mediated hepatoprotection. [ABSTRACT FROM AUTHOR]

The imbalance in metal homeostasis can be associated with several human diseases, and exposure to increasing concentrations of metals promotes cell stress and toxicity. Therefore, understanding the cytotoxic effect of metal imbalance is important to unravel the biochemical mechanism of homeostasis and the action of potential protective proteins against metal toxicity. Several studies, including gene deletion in yeast, provide evidence indicating the possible indirect involvement of cochaperones from the Hsp40/DNAJA family in metal homeostasis, possibly through modulating the activity of Hsp 70.This work first investigated the effect of zinc and copper on the conformation and function of the human Hsp40 cochaperone DNAJA1, a zinc-binding protein. DNAJA1 was capable to complement the phenotype of a yeast strain deleted of the ydj1 gene, which was more sensitive to the presence of zinc and copper than the wild-type strain. To gain further insight about the role of the DNAJA family in metal binding, the recombinant human DNAJA1 protein was studied. Zinc removal from DNAJA1 affected both its stability and ability to act as a chaperone, i.e., to protect other proteins from aggregation. The reintroduction of zinc restored the native properties of DNAJA1 and, surprisingly, the addition of copper partially restored the native properties. [Display omitted] • Human DNAJA1 is capable to complement the phenotype of a yeast strain deleted of the ydj1 gene. • Zinc removal from DNAJA1 affected both its stability and ability to act as a chaperone. • The reintroduction of either zinc restored the native properties of DNAJA1. • The reintroduction of either copper partially restored the native properties of DNAJA1. [ABSTRACT FROM AUTHOR]

Context • Lung squamous cell carcinoma (LUSC) accounts for 30% of non-small-cell lung cancers (NSCLC), and an effective pharmacological treatment for LUSC isn’t yet available. The Xihuang Pill is a potent Chinese medicinal preparation widely prescribed for the management of LUSC. Objective • The study intended to use the network-pharmacology method to ascertain the effective active ingredients, targets of action, and cellular-signal transduction involved in the prevention and treatment of LUSC when using the Xihuang Pill and to identify the mechanism of action of the pills against LUSC, to provide a more adequate scientific basis for subsequent studies. Design • The research team performed a genetic study. Setting • The study took place at Shanghai. Outcome Measures • The research team: (1) created the feature sets, for both the LUSC and normal features, using the Cancer Genome Atlas’ (TCGA’s) LUSC dataset; (2) performed a weighted correlation network analysis (WGCNA) of the differentially expressed genes (DEGs) using the R package WGCNA; (3) searched for the chemical components of the Xihuang Pill using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Herb Group Identification Platform, and (4) selected the novel the Matthews correlation coefficient (MCC) algorithm to screen the hub genes. Results • The study found 8713 DEGs between the LUSC and normal groups. The top ten, important, downregulated genes included: (1) advanced glycosylation end product (AGER), (2) chitinase, acidic pseudogene 2 (CHIAP2), (3) CD300 molecule like family member G (CD300LG), (4) solute carrier family 6 member 4 (SLC6A4), (5) carboxypeptidase B2 (CPB2), (6) claudin 18 (CLDN18), (7) gamma-glutamyltransferase light chain 1 (GGTLC1), (8) gastrokine 2 (GKN2), (9) progastricsin (PGC), and (10) pulmonary surfactant-associated protein C (SFTPC). The top 10 upregulated genes included: (1) cancer susceptibility 9 (CASC9), (2) homeobox C13 (HOXC13), (3) keratin 6a (KRT6A), (4) desmoglein 3 (DSG3), (5) keratin 16 (KRT16), (6) forkhead box E1 (FOXE1), (7) preferentially expressed antigen in melanoma (PRAME), (8) calmodulin-like protein 3 (CALML3), (9) KRT68, and (10) aldo-keto reductase family 1 member B10 (AKR1B10). The study found 41 active ingredients and 843 targets for the Xihuang Pill. The PPI network included 10 hub genes, including cyclin dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), pololike kinase 1 (PLK1), aurora kinase B (AURKB), baculoviral IAP repeat containing 5 (BIRC5), cyclin A2 (CCNA2), aurora kinase A (AURKA), centrosome-associated protein E (CENPE), and threonine tyrosine kinase (TTK), which were the principal target genes at the core of the gene-pathway network for the drug compound to central-target relationship. The enrichment analyses used the overlapping genes and the 10 hub genes and found 390 biological processes (BPs), 25 molecular functions (MFs), 43 cellular components (CCs), and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The main enrichment occurred in the regulation of protein serine-threonine kinase activity, mitotic nuclear division, progesterone-mediated oocyte maturation, and the cell cycle. Conclusions • The study found the targets and relevant pathways of the hub genes of Xihuang Pill using biological analysis and molecular docking and demonstrated the interactions of critical chemical compounds with the hub’s targeted genes were. More research is necessary to further determine whether the Xihuang Pill can improve LUSC patients’ survival rate by regulation of those genes. [ABSTRACT FROM AUTHOR]

Isoniazid is a synthetic antimicrobial and one of the most essential first-line drugs used in the treatment of tuberculosis. In addition, isoniazid has been used as a prophylactic drug for patients with latent Mycobacterium tuberculosis infection to prevent the reactivation of the disease. It is a prodrug that is activated by catalase-peroxidase (KatG) enzyme. Catalase peroxidase enzyme converts isoniazid to reactive species. Isoniazid reactive species inhibit enoyl acyl-carrier-protein reductase (InhA) enzyme, which is involved in the biosynthesis of fatty acids of mycobacteria. Isoniazid is metabolized by amidase enzyme into isonicotinic acid and hydrazine. Chronic toxicity of isoniazid results in hepatotoxicity and peripheral neuropathy. For active tuberculosis, isoniazid is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. Multiple extensively and totally drug-resistant strains of Mycobacterium tuberculosis were reported. Due to the development of Mycobacterium tuberculosis resistance to isoniazid, a continuous search for new drugs is a demand to combat this global problem. [ABSTRACT FROM AUTHOR]

Cisplatin (CisPt), a platinum-based chemotherapeutic widely used in the treatment of various cancers, has multiple mechanisms of action, including nuclear DNA (nDNA) and mitochondrial DNA (mDNA) damage and cytoskeletal perturbations affecting, in turn, the membrane transporter activity. CisPt binding to proteins and enzymes may modulate its biochemical mechanism of action and is associated with cancer cell resistance to the drug. In this work, we investigate the interaction between cisplatin and angiogenin (Ang), a protein strongly expressed in many types of cancer and a potent angiogenic factor. The adduct formed upon reaction of CisPt with Ang (Ang@CisPt) was characterized by X-ray crystallography to evidence the exact platination site and by UV-visible (UV-vis) absorption and circular dichroism (CD) spectroscopies to shed light on any possible change in the protein conformation. Furthermore, high-resolution electrospray ionization (ESI) mass spectrometry was utilized to evaluate the Ang : CisPt stoichiometry of the Ang@CisPt adduct. The effect of the Ang@CisPt adduct on a prostate cancer cell line (PC-3) was tested by colorimetric assays in terms of cell viability, at both levels of nuclear and mitochondrial damage, and reactive oxygen species (ROS) production. Cellular imaging by laser scanning confocal microscopy (LSM) was utilized to scrutinize the cytoskeleton actin reorganization and the lysosome and mitochondria organelle perturbation. These studies highlight the possibility of new molecular pathways and targets for CisPt activity. [ABSTRACT FROM AUTHOR]

Pistacia lentiscus L. var. chia resin (Chios Mastiha), the first natural chewing gum, is widely used in Mediterranean cuisine and has been used in traditional medicine from ancient times. Regarding its chemical composition, Chios Mastiha is known to be rich in triterpenes. Triterpenes have a similar structure to glucocorticoids (GCs), the steroid hormones that exert strong anti-inflammatory activities and play crucial roles in the regulation of cellular metabolism. To simplify the characterization of the bioactive compounds of Mastiha resin, three different polarity fractions were isolated and were further analyzed regarding their main chemical composition and an assessment of their biological activities. The biological assessment focused on the evaluation of the potential anti-proliferative, anti-inflammatory, and apoptotic activities as well as the possible interference of the three different polarity Mastiha fractions with the glucocorticoid receptor signaling, with the aim of characterizing the biochemical mechanisms of the actions of the Mastiha fraction. Applying MTT cell viability assay, luciferase/β-galactosidase assay, and Western blot analysis showed that Chios Mastiha apolar, medium-polar, and polar fractions reduced the HEK293 cell viability in a dose-dependent manner, possibly by mitochondrial-mediated induction of apoptosis. Medium-polar and polar Mastiha fractions also suppressed the GR and NF-κΒ transcriptional activation and the p65 protein levels. These activities were accompanied by the modulation of protein levels of regulatory molecules playing a crucial role in cellular energy homeostasis, such as GR, phosphoenolpyruvate carboxykinase (PEPCK), and/or peroxisome proliferator-activated receptor alpha (PPARα), and by the induction of phosphorylation and the activation of the AMP-activated protein kinase (AMPK). The medium-polar fraction was found to be enriched in triterpenes, such as lupeol, 24Z-masticadienonic acid methyl ester, and 24Z-isomasticadienonic acid methyl ester, and it was the most active one, so we propose that triterpenes in medium-polar fraction are possibly the bioactive compounds responsible for Mastiha's regulatory actions on energy metabolism and anti-inflammatory activities via interference with GR, NF-κΒ, and AMPK signaling. This highlights its potential applications in many fields of pharmaceutical, cosmetic, and nutraceutical interest. [ABSTRACT FROM AUTHOR]

Fraser's photinia 'Red Robin' (Photinia x fraseri Dress, Rosaceae family) is an important primary ornamental landscaping species with optimal hedge or screen effects and low maintenance, but it is difficult to root when propagated by cuttings, although high concentrations of phytohormones are used to optimize rhizogenesis. To our knowledge, there is currently no feasible enhanced method for photinia vegetative propagation through stem cuttings, using seaweed extract-based biostimulants as root promoters. Given the economic importance of the species, this research aims to assess the effects of indole-3-butyric acid (IBA) and seaweed extract-based stimulators on the quality of photinia 'Red Robin' cuttings, in terms of rooting indicators and ground and aboveground agronomic features. The treatments applied were different concentrations of commercial rooting stimulators compared to an untreated control: C0: distilled water; Rhizopon AA: 1% IBA (R1); Kelpak®: 2 mL L−1 (K2); Kelpak®: 3 mL L−1 (K3); Goteo®: 2 mL L−1 (G2); Goteo®: 3 mL L−1 (G3). The first results showed different responses to adventitious rhizogenesis under IBA and both seaweed extract treatments. At 70 DAC (days after cutting), the seaweed extract stimulated the production of over 80% of cuttings with callus; at 240 DAC, the percentage of rooted cuttings treated under R1 was the highest = 34.3%; the worst results were obtained by both biostimulant treatments at the highest doses: K3 = 21.3% and G3 = 20.7%. Furthermore, R1 produced 3.07 roots per cutting, which was 50% higher than the average of all other treatments. The applications of Kelpak® and Goteo® biostimulants, at both concentrations, resulted in an inhibition of root length with values below the untreated control. Rooted cuttings under R1 showed the highest ground (0.35 g) and aboveground (0.47) dry value. Neither seaweed extract, Kelpak® or Goteo®, at different concentrations, improved both the ground and above-ground weights of rooted cutting, compared to the untreated control, indicating that these natural products are not suitable for Fraser's photinia 'Red Robin' propagation using this methodology. The overall quality of cuttings in IBA treatment was the strongest, with 1%, being the optimum concentration. Further research must be conducted to propose effective agronomic protocols by investigating application methods, doses and number of applications, and to clarify the biochemical and molecular mechanisms of action of these seaweed extracts. [ABSTRACT FROM AUTHOR]

Aims The study reports the antifungal and antiaflatoxigenic mechanism activity of freeze-dried culture filtrate of Streptomyces philanthi RL-1-178 (DCF RL-1-178) against two aflatoxigenic strains (Aspergillus parasiticus and A. flavus) and identification of its active component. Methods and Results Significant inhibition in ergosterol biosynthesis by the DCF RL-1-178 appeared on the plasma membrane. Moreover, the DCF RL-1-178 showed dose-dependent inhibition of methylglyoxal (MG) (an aflatoxin inducer) biosynthesis and exhibited a novel antiaflatoxigenic action mechanism. Significant impairments in enzymatic [superoxide dismutase (SOD) and catalase (CAT)] and nonenzymatic [oxidized and reduced glutathione (GSH) and ratio of oxidized and reduced glutathione (GSSG)] anti-oxidative defense molecules were observed in the two aflatoxigenic cells. The active component of the DCF RL-1-178 was identified as natamycin. The natamycin exhibited against A. parasiticus and A. flavus with the minimum inhibitory concentration (MIC) values of 0.5 and 1.0 µg ml−1, respectively, while the minimum fungicidal concentration values were the same (4.0 µg ml−1). Conclusions The DCF RL-1-178 containing natamycin exhibited the following effects: (1) inhibition of cellular ergosterol biosynthesis on plasma membrane, (2) reduction in MG (aflatoxin inducer) confirmed novel antiaflatoxigenic mechanism of action, and (3) caused remarkable debasement in antioxidant defense enzymes (SOD and CAT) and nonenzymatic defense molecules (GSH and GSSG) revealing biochemical mechanism of action. [ABSTRACT FROM AUTHOR]

Cancer is one of the major healthcare challenges across the globe. Several anticancer drugs are available on the market but they either lack specificity or have poor safety, severe side effects, and suffer from resistance. So, there is a dire need to develop safer and target-specific anticancer drugs. More than 85% of all physiologically active pharmaceuticals are heterocycles or contain at least one heteroatom. Nitrogen heterocycles constituting the most common heterocyclic framework. In this study, we have compiled the FDA approved heterocyclic drugs with nitrogen atoms and their pharmacological properties. Moreover, we have reported nitrogen containing heterocycles, including pyrimidine, quinolone, carbazole, pyridine, imidazole, benzimidazole, triazole, β-lactam, indole, pyrazole, quinazoline, quinoxaline, isatin, pyrrolo-benzodiazepines, and pyrido[2,3-d]pyrimidines, which are used in the treatment of different types of cancer, concurrently covering the biochemical mechanisms of action and cellular targets. [ABSTRACT FROM AUTHOR]

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Currently, recent innovations describe the preparation and use of platelet concentrates to stimulate tissue regeneration and healing of both hard and soft tissues. Platelet-rich fibrin (PRF) corresponds to the second generation of these preparations. Its mechanism of action based on the growth factors found in platelets favors reparative processes at the cellular level in the surgical area. The present observational, analytical, and descriptive research aims to study biological properties and the use of PRF in root coverage procedures. [ABSTRACT FROM AUTHOR]

Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate. [ABSTRACT FROM AUTHOR]

• O/W Emulsion was found to have good kinetic stability. • Formulating Oil-in-water emulsion using Zingiber Officinal, Mentha Arvensis and Cuminum Cyminum plants extracts. • The O/W emulsion shows good therapeutic potential. • Tween-80 and Span-80 are highly efficient emulsifiers even at very low concentration. • The physicochemical properties confirm emulsion stability. Emulsion is a biphasic dosage form consisting of a distributed phase covering droplets distributed uniformly within an adjacent liquid, which constitutes the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize thermodynamically unstable emulsion. Different types of emulsion, including water-in-oil (W/O), oil-in-water (O/W), microemulsions, and multiple emulsions, are employed for delivering specific drugs within the body. They can be used to provide nutraceuticals as a medicine delivery mechanism. In present research project the aqueous extracts of three plants i.e. Zingiber Officinal, Mentha Arvensis and Cuminum Cyminum were combined in formulation of oil-in-water emulsion. Different analytical techniques were employed to characterized the sample. The foremost parameter was to determine the organoleptic properties (color, odor and texture). Afterwards, viscosity, electrical conductivity, thermal stability, Karl Fischer titration, and pH studies indicated the stability of the formulation. The continuous phase showed no visible coalescence or sedimentation in SEM image. The infrared spectra identify the presence of secondary metabolites, PDI and AAS were the characterization procedures adapted, that reveal the sample to be free of toxic constituents. The sample was subjected to deoxyribose degradation test. We used different concentration 0.01, 0.02, 0.03 and 0.05 %. The highest potential was recorded 12.71 % at Conc. 0.05 %. It was further confirmed by antioxidant DPPH assay. Same concentrations were used for antioxidant assay. The sample emulsion shows good potential 16 and 20 % at concentration 0.10 and 0.20 %. Highest potential 27 % was observed at highest concentration 0.80 %. We also performed the metal iron chelation activity. As compared to control O/W emulsion shows 7.78 % activity at concentration 0.05 %. It was further increases with increase in concentration i.e. 17.41, 19.13 and 23.15 % at conc. 0.1, 0.2 and 0.8 %. It was found that the sample is stable and less toxic. The primary screening of the sample gives the basis for future use however, further molecular studies are needed to decode the exact biochemical mechanism of action. [ABSTRACT FROM AUTHOR]

Background: Ruminants consume pasture and forages, but occasionally they do not have the necessary capacity for this, affecting digestibility. One of the strategies to improve quality is the utilization of exogenous enzymes that break down the structure of the cell wall, and permit better nutrient intake. Aim. To conduct a comprehensive study on the action mechanisms of exogenous fibrolytic enzymes in ruminant nutrition. Development: Plant cell wall is made of cellulose, hemicellulose, and lignin. The cellulases, hemicellulases, and lignocellulolytic enzymes are engaged in their degradation, being used satisfactorily in the diet to enhance digestibility with positive effects on other species’ production. Conclusions: This practice favors greater nutrient availability for digestion and absorption, and it contributes to the improvement of physiological processes, and on many occasions, it is evidenced through livestock yield increases. [ABSTRACT FROM AUTHOR]

Background and purpose: Therapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation. Methods: An international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion. Results: These recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5 °C) hypothermia was identified as the most promising treatment strategy. Conclusions: These recommendations provide a general outline for the use of TH afterminimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population. [ABSTRACT FROM AUTHOR]

Skin aging is a biological process leading to visible skin alterations. The mechanism of action, clinical efficacy and tolerance of a novel anti-wrinkle technology were evaluated in two skin care products formulated for different skin types. Two single-arm monocentric, open-label observational clinical studies, which were 56 days long, evaluated a cream-gel (n = 30) and a cream (n = 33) on the face and neck. Morphometric analyses of five types of wrinkles were performed at 0, 7, 28 and 56 days. Structural changes in extracellular matrix (ECM) including collagen, elastin and hyaluronic acid (HA) were visualized and quantified by histochemical imaging after daily treatment of skin explants for 6 days. Protein and gene expression related to barrier and hydration were analyzed using ELISA and qRT-PCR, respectively, in a reconstituted human skin model treated daily for 48 h. A decrease in wrinkle dimensions was found in the majority of parameters after 28 days of treatment. Collagen, elastin, HA, procollagen type I, hyaluronan synthases, HAS2 and HAS3 were all stimulated. Based on significant and consistent changes in our investigations, we conclude that the underlying mechanism of action of the novel anti-wrinkle technology could be the remodeling of dermal ECM, and both the test formulations were efficacious and well tolerated. [ABSTRACT FROM AUTHOR]

The article highlights newer therapies enhancing the treatment of inflammatory bowel disease (IBD), providing insights into their mechanisms of action, contraindications, and side effects. Topics include S1P receptor modulators, JAK inhibitors, and IL-23 inhibitors, with discussions on their efficacy and considerations for patient management.

Major progress has been made in the upfront treatment of multiple myeloma, but the disease ultimately relapses and leads to death in the vast majority of those afflicted. New treatment strategies and modalities are necessary to treat myeloma in relapse, particularly in cases of triple-refractory status defined by disease progression during or shortly after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibody therapy. In this manuscript, we review recent promising developments in the treatment of triple-class refractory myeloma including bispecific antibodies and T cell engagers, chimeric antigen receptor cellular therapies, as well as chemotherapeutics with novel mechanisms of action. [ABSTRACT FROM AUTHOR]

Zimbabwean pharmacists undergo university level education to understand the biochemical mechanisms and actions of medicines but are limited in their scope of practice. They are called medicines experts, yet they are not allowed to apply their specialized knowledge independently in direct patient management. We aim to obtain Zimbabwean pharmacists' perceptions on extending their scope of practice and to evaluate the Zimbabwe pharmacy honours degree curriculum to determine the competencies covered and whether these are in-line with an extended scope of practice. Qualitative semi-structured interviews with selected pharmacists were conducted to gather perspectives on the BPharm (Hons) curricula and extending pharmacists' scope of practice. A desktop review of the pharmacy curricula was also conducted to determine competencies covered. The results showed that pharmacists are keen to extend their scope of practice but the curriculum does not equip them with the required exit level competencies. "The pharmacist is obviously not equipped currently but needs to be involved in direct patient care such as identifying and managing medicine therapy problems, prescription extension, ordering and reviewing laboratory data and administrationof vaccines and immunizations". There exists an opportunity for pharmacists to extend their scope of practice in order to achieve universal health coverage. [ABSTRACT FROM AUTHOR]

The methoxy substituent is prevalent in natural products and, consequently, is present in many natural product-derived drugs. It has also been installed in modern drug molecules with no remnant of natural product features because medicinal chemists have been taking advantage of the benefits that this small functional group can bestow on ligand–target binding, physicochemical properties, and ADME parameters. Herein, over 230 methoxy-containing small-molecule drugs, as well as several fluoromethoxy-containing drugs, are presented from the vantage point of the methoxy group. Biochemical mechanisms of action, medicinal chemistry SAR studies, and numerous X-ray cocrystal structures are analyzed to identify the precise role of the methoxy group for many of the drugs and drug classes. Although the methoxy substituent can be considered as the hybridization of a hydroxy and a methyl group, the combination of these functionalities often results in unique effects that can amount to more than the sum of the individual parts. [Display omitted] • There are over 230 methoxy-containing small-molecule drugs. • The role of the methoxy group was elucidated through SAR and X-ray structures. • Advantages (e.g., binding) and disadvantages (e.g., metabolism) are discussed. • The combination of O and CH 3 results in unique hydrophilic and lipophilic effects. • Drugs containing the fluoromethoxy group were also compared and discussed. [ABSTRACT FROM AUTHOR]

• Chemical characterization of Trachyspermum ammi essential oil (TAEO). • TAEO showed potent antifungal activity against Aspergillus flavus. • TAEO causes alteration in fungal cell membrane and its metabolic activity. • Molecular dynamics revealed cell membrane as a potential target site of TAEO. • The study demonstrated the potential of TAEO as green antifungal agent. The present investigation explored the antifungal effectiveness of Trachyspermum ammi essential oil (TAEO) against Aspergillus flavus , aflatoxin B 1 (AFB 1) contamination, and its mechanism of action using biochemical and computational approaches. The GC–MS result revealed the chemical diversity of TAEO with the highest percentage of γ-terpinene (39 %). The TAEO exhibited minimum inhibitory concentration against A. flavus growth (0.5 µL/mL) and AFB 1 (0.4 µL/mL) with radical scavenging activity (IC 50 = 2.13 µL/mL). The mechanism of action of TAEO was associated with the alteration in plasma membrane functioning, antioxidative defense, and carbon source catabolism. The molecular dynamic result shows the multi-regime binding of γ-terpinene with the target proteins (Nor1, Omt1 , and Vbs) of AFB 1 biosynthesis. Furthermore, TAEO exhibited remarkable in-situ protection of Sorghum bicolor seed samples against A. flavus and AFB 1 contamination and protected the nutritional deterioration. Hence, the study recommends TAEO as a natural antifungal agent for food protection against A. flavus mediated biodeterioration. [ABSTRACT FROM AUTHOR]

The extensive consumption of antibiotics has been reported to significantly promote the generation of antibiotic resistance (ABR), however, a quantitative causal relationship between antibiotic exposure and ABR response is absent. This study aimed to pinpoint the accurate regulatory concentration of fluoroquinolones (FQs) and to understand the biochemical mechanism of the mutual action between FQ exposure and FQ resistance response. Highly sensitive analytical methods were developed by using UPLC-MS/MS to determine the total residual, extracellular residual, total intracellular, intracellular residual and intracellular degraded concentration of three representative FQs, including ciprofloxacin (CIP), ofloxacin (OFL) and norfloxacin (NOR), with detection limits in the range of 0.002–0.057 μg/L, and recoveries in the range of 80–93%. The MICs of Escherichia coli (E. coli) were 7.0–31.4-fold of the respective MIC 0 after 40-day FQ exposure, and significant negative associations were discovered between the intracellular (residual, degraded or the sum) FQ concentrations and FQ resistance. Transcriptional expression and whole-genome sequencing results indicated that reduced membrane permeability and enhanced multi-drug efflux pumps contributed to the decreasing intracellular concentration. These results unveiled the pivotal role of intracellular concentration in triggering FQ resistance, providing important information to understand the dose-response relationship between FQ exposure and FQ resistance response, and ascertain the target dose metric of FQs for eliminating FQ resistance crisis. [Display omitted] • A UPLC-MS/MS method was developed to determine five concentration metrics of FQs. • FQs induced irreversible antibiotic resistance of E. coli. • Intracellular FQ concentrations sharply decreased in the early stage of evolution. • FQ resistance negatively associated with intracellular concentrations of FQs. • Variation of membrane permeability and efflux pumps contributed to the result. [ABSTRACT FROM AUTHOR]

Medical oxygen-ozone (O2-O3) is a successful therapeutic approach accounting on the assessed beneficial action of ozone in the range 30–45 μg/ml (expanded range 10–80 μg/ml according to different protocols), as in this dosage range ozone is able to trigger a cellular hormetic response via the modulating activity of reactive oxygen species (ROS), as signaling molecules. The ozone-dependent ROS-mediated fatty acid oxidation leads to the formation of lipid ozonization products (LOPs), which act as signal transducers by triggering ROS signaling and therefore mitohormetic processes. These processes ultimately activate survival mechanisms at a cellular level, such as the Nrf2/Keap1/ARE system activation, the AMPK/FOXO/mTOR/Sir1 pathway and the Nrf2/NF-kB cross talk. Furthermore, indirectly, via these pathways, LOPs trigger the HIF-1α pathway, the HO-1 signaling and the NO/iNOS biochemical machinery. Ozone-driven shift of cytokine activation pathways, from pro-inflammatory to anti-inflammatory immediately afterwards, also exert direct immunoregulatory effects on regulatory T lymphocytes as well as on the intestinal microbiota, which in turn can affect immune response thus influencing the progression of the disease. In this review, we will describe the biological and biochemical mechanisms of action of ozone therapy with the aim of evaluating both positive and critical aspects of ozone use as a therapeutic adjuvant in the light of emerging viral infections, such as SARS-CoV-2 and microbiome-associated disorders related to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Nitrosative stress is an adverse physiological condition mediated by an excessive level of reactive nitrogen species (RNS). RNS react with the different macromolecules in vivo and result in the inactivation of these molecules. But the mechanism to counteract the effect of nitrosative stress is poorly understood. Escherichia coli is one of the best understood and well-studied microorganism. Although several studies have been reported on Escherichia coli to characterize the effect of various stress response but fewer works are there to see the effect of nitrosative stress. Escherichia coli encounter numerous stresses during its growth, survival, and infection. They respond to various stress conditions by activating common regulator proteins and thiols. These stress conditions result in the accumulation of these regulator proteins and thiols that allow cells to adjust to specific stress situations, conferring stress tolerance and survival. In this review, different enzymatic and non-enzymatic mechanisms to counteract the effect of nitrosative stress in Escherichia coli have been discussed and a hypothesis for the working mechanism of hybrid cluster protein that helps to combat nitrosative stress has been proposed. Here, we have tried to give a clear scenario about the mode of action of stress-responsive elements present in Escherichia coli. [ABSTRACT FROM AUTHOR]

A review of literary sources shows the prevalence of the problem of the development of oxidative stress as a side effect of many pathological processes in animals and humans. It is essential to develop ways and means of its prevention and correction since its correction can be a non-specific therapy in developing many pathological processes. The development of oxidative stress caused deviations in redox processes, the permeability of cellular membranes, and their integrity. Overcoming the effects of oxidative stress requires bio-preparations with high bioavailability, which can stimulate the body's natural antioxidant defense system and neutralize the toxic effects of xenobiotics. Reducing the manifestation of oxidative stress is often adapting the body's natural antioxidant protection system to increase the supply or formation of reactive oxygen species and free radical oxidation products. Macro- and microelements are absorbed by the body of animals and humans mainly through the digestive system. To correct deficiencies of certain elements, mineral, and vitamin-mineral supplements used in the diet, and drugs for parenteral administration - under acute deficiency. Chelates of chemical elements are increasingly used in therapeutic practice, as they are characterized by higher bioavailability compared to organic and inorganic salts of the same elements. The use of compounds with higher bioavailability makes it possible to introduce a smaller amount of the drug in terms of metal, which will avoid the irritating effect and improve the organoleptic indicators, preserving or even enhancing the therapeutic effect. Chelates have a lower irritating effect at the same concentrations as in saline solutions. Therefore, the study of the biochemical mechanisms of action of the drug (in particular, in the correction of oxidative stress) is an urgent issue that prompts us to study it to develop a drug with high bioavailability and confirm its effectiveness. [ABSTRACT FROM AUTHOR]

Real-time, advanced diagnostics of the biochemical state within cells remains a significant challenge for research and development, production, and application of cell-based therapies. The fundamental biochemical processes and mechanisms of action of such advanced therapies are still largely unknown, including the critical quality attributes that correlate to therapeutic function, performance, and potency and the critical process parameters that impact quality throughout cell therapy manufacturing. An integrated microfluidic platform has been developed for in-line analysis of a small number of cells via direct infusion nano-electrospray ionization mass spectrometry. Central to this platform is a microfabricated cell processing device that prepares cells from limited sample volumes removed directly from cell culture systems. The sample-to-analysis workflow overcomes the labor intensive, time-consuming, and destructive nature of existing mass spectrometry approaches for analysis of cells. By providing rapid, high-throughput analyses of the intracellular state, this platform enables untargeted discovery of critical quality attributes and their real-time, in-process monitoring. [ABSTRACT FROM AUTHOR]

Apolipoprotein D is a chordate gene early originated in the Lipocalin protein family. Among other features, regulation of its expression in a wide variety of disease conditions in humans, as apparently unrelated as neurodegeneration or breast cancer, have called for attention on this gene. Also, its presence in different tissues, from blood to brain, and different subcellular locations, from HDL lipoparticles to the interior of lysosomes or the surface of extracellular vesicles, poses an interesting challenge in deciphering its physiological function: Is ApoD a moonlighting protein, serving different roles in different cellular compartments, tissues, or organisms? Or does it have a unique biochemical mechanism of action that accounts for such apparently diverse roles in different physiological situations? To answer these questions, we have performed a systematic review of all primary publications where ApoD properties have been investigated in chordates. We conclude that ApoD ligand binding in the Lipocalin pocket, combined with an antioxidant activity performed at the rim of the pocket are properties sufficient to explain ApoD association with different lipid-based structures, where its physiological function is better described as lipid-management than by long-range lipid-transport. Controlling the redox state of these lipid structures in particular subcellular locations or extracellular structures, ApoD is able to modulate an enormous array of apparently diverse processes in the organism, both in health and disease. The new picture emerging from these data should help to put the physiological role of ApoD in new contexts and to inspire well-focused future research. [ABSTRACT FROM AUTHOR]

Agarwood from Aquilaria plants, also known as Chen Xiang (沉香), is traditionally used for the treatment of abdominal pain and as a sedative. Because of the great demand and the rareness of agarwood, extensive harvesting of Aquilaria plants has nearly led to the extinction of the species. To fully utilize this resource, the use of different parts of Aquilaria needs to be investigated. This article will focus on the pharmacological properties and the mechanism of action of different parts of Aquilaria plants. [ABSTRACT FROM AUTHOR]

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma. [ABSTRACT FROM AUTHOR]

Background. Solute carrier family 12 member 5 (SLC12A5) has been reported to play an oncogenic role in certain malignancies. Its prognostic roles and immune mechanisms of action in human cancers, however, remain largely unknown. Methods. Data derived from TCGA, GEPIA, and TIMER databases were utilized to delve into the expressing patterns, prognostic values, clinical significances, and tumor immunity of SLC12A5 in tumors. Additionally, the association of SLC12A5 expressions with tumor mutation burden (TMB), methyltransferases, and mismatch repairs (MMRs) was also analyzed. Results. Herein, we observed that SLC12A5 was significantly overexpressed in various malignancies, and SLC12A5 levels correlated with overall survival, disease-specific survival, and tumor stage of certain cancers. Furthermore, we noticed that SLC12A5 was distinctly associated with methyltransferases, mismatch repair proteins, TMB, and MSI in human cancers. Conclusions. SLC12A5 may act as a potential prognostic and immunological biomarker and therapeutic target for human cancers. [ABSTRACT FROM AUTHOR]