Biological Actions Research Articles

Therapeutic effect of allicin in a mouse model of intracerebral hemorrhage

Natural compounds with sulfur moiety produce various biological actions that may be beneficial for the therapies of several devastative disorders of the central nervous system. Here we investigated potential therapeutic effect of allicin, an organosulfur compound derived from garlic, in a mouse model of intracerebral hemorrhage (ICH) based on intrastriatal collagenase injection. Daily intraperitoneal administration of allicin (50 mg/kg) from 3 h after induction of ICH afforded neuroprotective effects, as evidenced by the increase of surviving neurons in the hematoma, reduction of axonal transport impairment, and prevention of axon tract injury. In addition, allicin inhibited accumulation of activated microglia/macrophages around the hematoma and infiltration of neutrophils within the hematoma. Allicin also suppressed ICH-induced mRNA upregulation of pro-inflammatory factors such as interleukin 6 and C-X-C motif ligand 2 in the brain, suggesting its anti-inflammatory effect. Moreover, ICH-induced increase of malondialdehyde as well as decrease of total glutathione in the brain was attenuated by allicin. Finally, allicin-treated mice showed better recovery of sensorimotor functions after ICH than vehicle-treated mice. These results indicate that allicin produces a therapeutic effect on ICH pathology via alleviation of neuronal damage, inflammatory responses and oxidative stress in the brain.

Triarylphosphonium compounds as effective vectors for mitochondria-targeted delivery systems: decoration strategies and prospects for clinical application

Mitochondrial dysfunctions lead to the emergence and development of a large number of diseases. The present review gives the first systematic survey of various aspects of studies of mitochondria-targeted nanosystems containing triphenylphosphonium vector groups providing targeted delivery of drug substances to these organelles. Approaches to the design of components and various nanoparticles bearing these groups are summarized and analyzed. The relationship between the key parameters of triphenylphosphonium nanoparticles (chemical composition, size, shape, ζ-potential, drug loading, drug encapsulation efficiency, <i>etc</i>.) and the biological action is discussed; in some cases, the mechanism of mitochondria targeting is given. The design principles and preparation methods for mitochondria-targeted triphenylphosphonium delivery nanosystems are of interest to researchers in the field of nanomaterials, nanotechnology, molecular biology, biotechnology and pharmaceutical chemistry. <br> The bibliography includes 243 references.

Platinum(IV)-based prodrugs as an alternative to Pt(II)-based drugs: synthesis and biological action

The chemotherapy with cisplatin and its analogues widely used in medical practice is associated with undesirable side effects caused by non-selective ligand exchange and binding of the complexes to various biomolecules in the body. An alernative to classical platinum(II)-based drugs are platinum(IV) prodrugs, that is, platinum(II) complexes additionally modified with diverse biologically active axial ligands, including known pharmaceutical products. In recent years, quite a few studies devoted to the design of effective Pt(IV) prodrugs have been published, with some of the developed agents being markedly superior to clinically used cisplatin and carboplatin in therapeutic efficacy. This review summarizes the synthetic approaches to the design of Pt(IV) prodrugs and modification of the axial ligands. The second part of the review is devoted to the biological activity of Pt(IV) prodrugs reported in the period from 2018 to 2023 and comparison of various approaches to the design of effective anticancer agents based on these compounds. The bibliography includes 239 references.

Research progress on structure, structure-activity relationship, and biological activity of Aconiti Lateralis Radix Praeparata polysaccharides

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.

Design, synthesis and molecular modeling of isatin-aminobenzoic acid hybrids as antibacterial and antibiofilm agents

Number of factors, including newly emerging infectious diseases and an increase in multi-drug resistant microbial pathogens with particular relevance for Gram-positive bacteria, make the treatment of infectious diseases in hospital-based healthcare a major challenge in the medical community. 4-Aminobenzoic acid (PABA), has demonstrated a variety of biological actions particularly, antimicrobial activity. In our study we coupled this vitamin-like molecule with different isatin derivatives. We investigated the antibacterial activity of the synthesized Schiff's bases. The compounds showed high selective activity against Gram-positive bacteria and showed weak or no activity against both Gram-negative bacteria and fungi. Compound 2a showed highest activity against S. aureus and B. subtilis (MIC 0.09 mmol/L). Additionally, these substances exhibit strong anti-B. Subtilis biofilm formation. We were able to shed insight on the binding mode of these new inhibitors using in silico docking of the compounds in the binding sites of a 3D structure of B. subtilis histidine kinase/Walk. The binding free energy of the compound 2a to the catalytic domain walk, of histidine kinase enzyme of B. subtilis bacteria, was calculated using molecular mechanics/generalized born surface area scoring. The key residues for macromolecule–ligand binding were postulated. The optimized 3D protein–ligand binding modes shed light on the B. subtilis HK/Walk–ligand interactions that afford a means to assess binding affinity to design new HK/Walk inhibitor as antibacterial agents.

Radiation-Induced Transfer of Charge, Atoms, and Energy within Isolated Biomolecular Systems.

In biological tissues, ionizing radiation interacts with a variety of molecules and the consequences include cell killing and the modification of mechanical properties. Applications of biological radiation action are for instance radiotherapy, sterilization, or the tailoring of biomaterial properties. During the first femtoseconds to milliseconds after the initial radiation action, biomolecular systems typically respond by transfer of charge, atoms, or energy. In the condensed phase, it is usually very difficult to distinguish direct effects from indirect effects. A straightforward solution for this problem is the use of gas-phase techniques, for instance from the field of mass spectrometry. In this review, we survey mainly experimental but also theoretical work, focusing on radiation-induced intra- and inter-molecular transfer of charge, atoms, and energy within biomolecular systems in the gas phase. Building blocks of DNA, proteins, and saccharides, but also antibiotics are considered. The emergence of general processes as well as their timescales and mechanisms are highlighted.

Secretory Conservation in Insulin Producing Cells: Is There a System-Level Law of Mass Action in Biology?

Altered secretion of insulin from pancreatic β-cells can manifest into disorders. For example, a lack of endogenously produced and/or secreted insulin results in Type 1 diabetes (and other associated subtypes). Pancreatic β-cells are the endocrine secretory cells that promote insulin secretion in response to glucose stimulation. Secretion in response to extracellular triggers is an interplay among various signaling pathways, transcription factors, and molecular mechanisms. The Mouse Insulinoma 6 (MIN6) cell line serves as a model system for gaining mechanistic insights into pancreatic β-cell functions. It is obvious that higher glucose consumption and increased insulin secretion are correlated. However, it has been reported that intracellular ATP levels remain ∼ constant beyond the extracellular glucose (EG) concentration of 10 mM. Therefore, any cause-effect relationship between glucose consumption (GC) and enhanced insulin secretion (eIS) remains unclear. We also found that total cellular protein, as well as total protein content in the culture "supernatant," remains constant regardless of varying EG concentrations. This indicated that eIS may be at the cost of (a) intracellular synthesis of other proteins and (b) secretion of other secretory proteins, or both (a) and (b), somehow coupled with GC by cells. To gain insights into the above, we carried out a transcriptome study of MIN6 cells exposed to hypoglycemic (HoG = 2.8 mM EG) and hyperglycemic (HyG = 25 mM EG) conditions. Expression of transcripts was analyzed in terms of Fragments Per Kilobase of transcript per Million mapped reads and Transcripts Per Million (FPKM and TPM) as well as values obtained by normalizing w.r.t. "∑(FPKM)" and "∑(TPM)." We report that HyG extracellular conditions lead to an ∼2-fold increase in insulin secretion compared to HoG measured by the enzyme-linked immunosorbent assay (ELISA) and transcripts of secreted proteins as well as their isoforms decreased in HyG conditions compared to HoG. Our results show for the first time that eIS in HyG conditions is at the cost of reduced transcription of other secreted proteins and is coupled with higher GC. The higher GC at increased extracellular glucose also indicates a yet undiscovered role of glucose molecules enhancing insulin secretion, since ATP levels resulting from glucose metabolism have been reported to be constant above an EG concentration of 10 mM. While extrapolation of our results to clinical implications is ambitious at best, this work reports novel cellular level aspects that seem relevant in some clinical observations pertaining to Type 1 diabetes. In addition, the conservatory nature of cellular secretions in insulin-secreting cells, discovered here, may be a general feature in cell biology.

Potential Benefits of Propolis in Large and Small Animal Practices: A Narrative Review of the Literature

Propolis is a resinous substance from a mixture of different plant parts and molecules bees compose. This narrative review article explored the application of propolis in large and small animal practices in PubMed, Scopus, and Google Scholar databases. Propolis is applied in different pharmaceutical forms. Due to its numerous biological actions, such as antimicrobial, anti-inflammatory, antioxidant, antiparasitic, antiulcer, antitumor, and immunomodulatory, propolis can improve animal health and production. Propolis could be used as an alternative treatment for many diseases, such as mastitis, lumpy skin disease, foot and mouth disease, reproductive disorders, and diarrhea in cattle. Moreover, it could improve weight gain in cattle. In equine, propolis has been used as a local anesthetic and for treating dermatomycosis, chronic bronchitis, and skin wounds. In pigs, propolis has been used to treat enzootic pneumonia and as a prophylaxis for gastrointestinal and respiratory diseases in weak pigs. Propolis has been applied to treat caseous lymphadenitis and parasitic diseases in sheep and goats. Furthermore, it improves the immune status of kids and the health status of late pregnant ewes. In dogs and cats, propolis has been applied to treat otitis externa, eye diseases, Cushing’s syndrome, and dermatophytosis. In dogs, propolis can treat transmissible venereal tumors. Moreover, propolis positively affects animal production, average daily gain and milk yield in sheep, growth of calves, lambs, and piglets, and cow’s milk nutritional quality. On the other hand, the addition of propolis to the diet of feedlot bulls and pigs has no effect on their feed intake, hematological, biochemical, and immunological parameters, nutrient digestibility, microbial synthesis, and carcass characteristics. Based on the available clinical studies, propolis has potential benefits for animal health in cattle, equine, sheep, goats, pigs, dogs, and cats. According to the available literature, propolis is a natural promising agent that can alternate conventional pharmaceuticals, particularly antibiotics. It improves animal health and production with no adverse effects and low cost. Most conducted studies on the efficacy of propolis on animal health and production are in vitro. Due to its scarcity, further controlled clinical trials are recommended to evaluate the exact usefulness of propolis in veterinary medicine and to obtain reliable conclusions on the benefits of propolis in animal health and production.

VDR promotes testosterone synthesis in mouse Leydig cells via regulation of cholesterol side chain cleavage cytochrome P450 (Cyp11a1) expression.

The vitamin D receptor (VDR) mediates the pleiotropic biological actions that include osteoporosis, immune responses and androgen synthesis.VDR is widely expressed in testis cells such as Leydig cells, Sertoli cells, and sperm. The levels of steroids are critical for sexual development. In the early stage of steroidogenesis, cholesterol is converted to pregnenolone (precursor of most steroid hormones) by cholesterol side-chain lyase (CYP11A1), which eventually synthesizes the male hormone testosterone. This study aims to reveal how VDR regulates CYP11A1 expression and affects testosterone synthesis in murine Leydig cells. The levels of VDR, CYP11A1 were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blot. Targeted relationship between VDR and Cyp11a1 was evaluated by dual-luciferase reporter assay. The levels of testosterone concentrations in cell culture media serum by enzyme-linked immunosorbent assay (ELISA). Phylogenetic and motif analysis showed that the Cyp11a1 family had sequence loss, which may have special biological functions during evolution. The results of promoter prediction showed that vitamin D response element (VDRE) existed in the upstream promoter region of murine Cyp11a1. Dual-luciferase assay confirmed that VDR could bind candidate VDREs in upstream region of Cyp11a1, and enhance gene expression. Tissue distribution and localizatio analysis showed that Cyp11a1 was mainly expressed in testis, and dominantly existed in murine Leydig cells. Furthermore, over-expression VDR and CYP11A1 significantly increased testosterone synthesis in mice Leydig cells. Active vitamin D3 (VD3) and Vdr interference treatment showed that VD3/VDR had a positive regulatory effect on Cyp11a1 expression and testosterone secretion. VDR promotes testosterone synthesis in male mice by up-regulating Cyp11a1 expression, which played an important role for male reproduction.

The Biological Action and Structural Characterization of Eryngitin 3 and 4, Ribotoxin-like Proteins from Pleurotus eryngii Fruiting Bodies.

Ribotoxin-like proteins (RL-Ps) are specific ribonucleases found in mushrooms that are able to cleave a single phosphodiester bond located in the sarcin-ricin loop (SRL) of the large rRNA. The cleaved SRL interacts differently with some ribosomal proteins (P-stalk). This action blocks protein synthesis because the damaged ribosomes are unable to interact with elongation factors. Here, the amino acid sequences of eryngitin 3 and 4, RL-Ps isolated from Pleurotus eryngii fruiting bodies, were determined to (i) obtain structural information on this specific ribonuclease family from edible mushrooms and (ii) explore the structural determinants which justify their different biological and antipathogenic activities. Indeed, eryngitin 3 exhibited higher toxicity with respect to eryngitin 4 against tumoral cell lines and model fungi. Structurally, eryngitin 3 and 4 consist of 132 amino acids, most of them identical and exhibiting a single free cysteinyl residue. The amino acidic differences between the two toxins are (i) an additional phenylalanyl residue at the N-terminus of eryngitin 3, not retrieved in eryngitin 4, and (ii) an additional arginyl residue at the C-terminus of eryngitin 4, not retrieved in eryngitin 3. The 3D models of eryngitins show slight differences at the N- and C-terminal regions. In particular, the positive electrostatic surface at the C-terminal of eryngitin 4 is due to the additional arginyl residue not retrieved in eryngitin 3. This additional positive charge could interfere with the binding to the SRL (substrate) or with some ribosomal proteins (P-stalk structure) during substrate recognition.

The Antioxidant Potential of Resveratrol from Red Vine Leaves Delivered in an Electrospun Nanofiber System.

Despite the wide pharmacological action of polyphenols, their usefulness is limited due to their low oral bioavailability, which is due to their low solubility and rapid first-pass metabolism. Red vine leaf extract is an herbal medicine containing several polyphenols, with resveratrol and polydatin as the main compounds exhibiting antioxidant and anti-inflammatory properties. In the first stage of the work, using the Design of Experiment (DoE) approach, the red vine leaf extract (50% methanol, temperature 70 °C, and three cycles per 60 min) was obtained, which showed optimal antioxidant and anti-inflammatory properties. In order to circumvent the above-described limitations and use innovative technology, electrospun nanofibers containing the red vine leaf extract, polyvinylpyrrolidone (PVP), and hydroxypropyl-β-cyclodextrin (HPβCD) were first developed. The optimization of the process involved the time of system mixing prior to electrospinning, the mixture flow rate, and the rotation speed of the collector. Dissolution studies of nanofibers showed improved resveratrol release from the nanofibers (over five-fold). Additionally, a PAMPA-GIT assay confirmed significantly better buccal penetration of resveratrol from this nanofiber combination (over ten-fold). The proposed strategy for electrospun nanofibers with the red vine leaf extract is an innovative approach to better use the synergy of the biological action of active compounds present in extracts that are beneficial for the development of nutraceuticals.

UHPLC-ESI-QTOF-MS/MS Profiling of Phytochemicals from Araticum Fruit (Annona crassiflora Mart.) and Its Antioxidant Activity.

Araticum is a native species of the Brazilian Cerrado with a high potential for exploitation. Several studies have stated that araticum is a rich source of phytochemicals with multifaceted biological actions. However, little information is available regarding the characterization of phytochemicals found in the pulp of this fruit. In this context, this study aimed to carry out a comprehensive characterization of phytochemicals present in the araticum pulp using ultra-high-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer (UHPLC-ESI-QTOF-MS/MS). The antioxidant potential of araticum pulp was also evaluated. UHPLC-ESI-QTOF-MS/MS profiling of the phytochemicals allowed for the identification and annotation of 139 phytochemicals, including organic acids, jasmonates, iridoids, phenolic compounds, alkaloids, annonaceous acetogenins, fatty acid derivatives, and other compounds. Among them, 116 compounds have been found for the first time in araticum pulp. Phenolic compounds and their derivatives represented about 59% of the phytochemicals identified in the extract. Moreover, araticum pulp showed high total phenolic compound content and antioxidant activity. The majority of identified phytochemicals have been associated with key roles in the plant's defense mechanisms against biotic and abiotic stress factors in the Cerrado environment. Furthermore, many of these phytochemicals found in the araticum pulp are already widely recognized for their beneficial effects on human health. Our findings showed that the araticum fruit contains different classes of phytochemicals that exert various biological activities, both in the plant itself and in humans.

Simultaneous removal of phosphorus, zinc, and lead from oligotrophic ecosystem by iron-driven denitrification: Performance and mechanisms

Based on the current situation of complex pollution caused in surface water by oligotrophic condition and heavy metal release from river and lake bottom sediments. This study aimed to achieve the simultaneous removal of nitrate, phosphorus, Zn2+ and Pb2+ through microbial approach. At nitrate concentration of 4.82 mg L−1, carbon to nitrogen ratio of 1.5, pH of 6.0, and Fe2+ concentration of 5.0 mg L−1, the nitrate removal efficiency of Zoogloea sp. FY-6 reached 95.17%. The addition of pollutants under these conditions resulted in 88.76% removal of total phosphorus at 18 h, and 85.46 and 78.59% removal of Zn2+ and Pb2+ respectively, and there was competition for adsorption between Zn2+ and Pb2+. Extracellular polymers and fluorescence excitation-emission substrates confirmed that Fe2+ reduced heavy metal toxicity through promoting bacterial production of secretions and promotes denitrification as a carbon source. Meanwhile, contaminant removal curves and Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy demonstrated the synchronous removal of Zn2+ and Pb2+ mainly through biological action and the formation of nanoscale iron oxides. Biological-iron precipitation also provided adsorption sites for phosphorus. This research provides the theoretical foundation for applying microorganisms to restore oligotrophic source water (rivers and lakes) containing complex pollutants.

Natriuretic Peptide Receptors (NPRs) as a Potential Target for the Treatment of Heart Failure.

Heart failure is defined as a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The natriuretic peptide is known to exert its biological action on the kidney, heart, blood vessels, renin-angiotensin system, autonomous nervous system, and central nervous system. The natriuretic peptide-natriuretic receptor system plays an important role in the regulation of blood pressure and body fluid volume through its pleiotropic effects. The clinical and animal studies suggest that natriuretic peptide-natriuretic receptors are important targets for the treatment of heart failure and other cardiovascular diseases. Even though attempts targeting natriuretic peptide receptors are underway for heart failure treatment, they seem insufficient despite the receptor systems' potential. This review summarizes natriuretic peptide-natriuretic receptor system's physiological actions and potential target for the treatment of heart failure. Natriuretic peptides play multiple roles in different parts of the body, almost all of the activities related to this receptor system appear to have the potential to be harnessed to treat heart failure or symptoms associated with heart failure.

An update on galanin and spexin and their potential for the treatment of type 2 diabetes and related metabolic disorders

Spexin (SPX) and galanin (GAL) are two neuropeptides widely expressed in the central nervous system as well as within peripheral tissues in humans and other species. SPX and GAL mediate their biological actions through binding and activation of galanin receptors (GALR), namely GALR1, GALR2 and GLAR3. GAL appears to trigger all three galanin receptors, whereas SPX interacts more specifically with GALR2 and GLAR3. Whilst the biological effects of GAL have been well-described over the years, in-depth knowledge of physiological action profile of SPX is still in its preliminary stages. However, it is recognised that both peptides play a significant role in modulating overall energy homeostasis, suggesting possible therapeutically exploitable benefits in diseases such as obesity and type 2 diabetes mellitus. Accordingly, although both peptides activate GALR’s, it appears GAL may be more useful for the treatment of eating disorders such as anorexia and bulimia, whereas SPX may find therapeutic application for obesity and obesity-driven forms of diabetes. This short narrative review aims to provide an up-to-date account of SPX and GAL biology together with putative approaches on exploiting these peptides for the treatment of metabolic disorders.

Potential Role of Natural Antioxidants in Countering Reperfusion Injury in Acute Myocardial Infarction and Ischemic Stroke.

Stroke and acute myocardial infarction are leading causes of mortality worldwide. The latter accounts for approximately 9 million deaths annually. In turn, ischemic stroke is a significant contributor to adult physical disability globally. While reperfusion is crucial for tissue recovery, it can paradoxically exacerbate damage through oxidative stress (OS), inflammation, and cell death. Therefore, it is imperative to explore diverse approaches aimed at minimizing ischemia/reperfusion injury to enhance clinical outcomes. OS primarily arises from an excessive generation of reactive oxygen species (ROS) and/or decreased endogenous antioxidant potential. Natural antioxidant compounds can counteract the injury mechanisms linked to ROS. While promising preclinical results, based on monotherapies, account for protective effects against tissue injury by ROS, translating these models into human applications has yielded controversial evidence. However, since the wide spectrum of antioxidants having diverse chemical characteristics offers varied biological actions on cell signaling pathways, multitherapy has emerged as a valuable therapeutic resource. Moreover, the combination of antioxidants in multitherapy holds significant potential for synergistic effects. This study was designed with the aim of providing an updated overview of natural antioxidants suitable for preventing myocardial and cerebral ischemia/reperfusion injuries.

Investigation of the impact of nonsynonymous mutations on thyroid peroxidase dimer.

Congenital hypothyroidism is one of the most common preventable endocrine disorders associated with thyroid dysgenesis or dyshormonogenesis. Thyroid peroxidase (TPO) gene defect is mainly responsible for dyshormonogenesis; a defect in the thyroid hormone biosynthesis pathway. In Bangladesh, there is limited data regarding the genetic etiology of Congenital Hypothyroidism (CH). The present study investigates the impact of the detected mutations (p.Ala373Ser, and p.Thr725Pro) on the TPO dimer protein. We have performed sequential molecular docking of H2O2 and I- ligands with both monomers of TPO dimer to understand the iodination process in thyroid hormone biosynthesis. Understanding homodimer interactions at the atomic level is a critical challenge to elucidate their biological mechanisms of action. The docking results reveal that mutations in the dimer severely disrupt its catalytic interaction with essential ligands. Molecular dynamics simulation has been performed to validate the docking results, thus realizing the consequence of the mutation in the biological system's mimic. The dynamics results expose that mutations destabilize the TPO dimer protein. Finally, principal component analysis exhibits structural and energy profile discrepancies in wild-type and mutant dimers. The findings of this study highlight that the mutations in TPO protein can critically affect the dimer structure and loss of enzymatic activity is persistent. Other factors also might influence the hormone synthesis pathway, which is under investigation.

Elexacaftor/VX-445–mediated CFTR interactome remodeling reveals differential correction driven by mutation-specific translational dynamics

Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report that variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry multiplexed with isobaric tandem mass tags was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knockdowns sensitize P67L to VX-445 and further enhance the trafficking correction of this variant. Partial inhibition of protein translation also mildly sensitizes P67L CFTR to VX-445 correction, supporting a role for translational dynamics in the rescue mechanism of VX-445. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize nonresponsive CFTR variants to known and available correctors.

An insight into the advances in ionic liquids and its applications in medicine

Ionic liquids (ILs) are intriguing non-molecular compounds of sole ions and have been emerging as major players with a wider application spectrum in the science and technological domains of nanoscience, synthesis, catalysis, extraction, analytics, electrochemistry, and biotechnology due to their highly customizable nature, outstanding capabilities, and greener alternative to conventional organic solvents. Aside from physical and chemical features and potentials, ionic liquids have higher biological activities that excite the curiosity of researchers, biochemists, ecologists, and medical professionals towards innovations and smart procedures. The evidence of ionic liquids' biological activity, including their antibacterial and cytotoxic capabilities, has been further explored and examined in light of their potential uses in drug production and drug delivery systems. The biological actions and their prospective applications, such as a revolutionary active pharmaceutical ingredient, ionic liquid (API-IL), in medicine, have been gaining special attention. The primary goal of this review is to elaborate on the enticing potential of chemical and biological characteristics and their advancements in ionic liquids for pharmaceutics and medicinal applications.

Recent Advancement in Synthesis and Bioactivities of 1,3,4-Oxadiazole.

Derivatives of 1,3,4-oxadiazole are effective in the treatment and cure of a wide range of diseases in medical chemistry, while industrial development has shown that they can be utilised as corrosion inhibitors and light-emitting diodes. The researchers discovered several promising synthetic strategies that created 1,3,4-oxadiazoles in extraordinarily high yields while using environmentally friendly methods. These compounds can potentially be used in a wide range of lifechanging applications. Stable isomeric oxadiazole forms of pleconaril, raltegravir, butalamine, fasiplon, oxolamine, and several other drugs are among the numerous potent and effective pharmaceuticals that are now on the market. Fasiplon, butalamine, raltegravir, and pleconaril treat HIV/AIDS patients. This article has attempted to bring attention to the chemistry and pharmacology of oxadiazole and its derivatives. Oxadiazole derivatives have been used extensively as prospective therapeutic agents in clinical research, and this has become standard practice. The use of biological and in-silico models has enabled scientists to identify more synthetic analogues of cancer prevention, antifungal, and anti-HIV medications. This article provides recent information regarding procedures for synthesizing 1,3,4-oxadiazoles and their biological actions on the body.