Ferroptosis, is an iron-dependent cell death, characterized by the accumulation of lipid reactive oxygen species, and various regulatory mechanisms influence the course of ferroptosis. The rapid increase in cardiovascular diseases(CVDs) is an extremely urgent problem. CVDs are characterized by the progressive deterioration of the heart and blood vessels, eventually leading to circulatory system disorder. Accumulating evidence, however, has highlighted crucial roles for ferroptosis in CVDs. Hydrogen sulfide plays a significant part in anti-oxidative stress, which may participate in the general mechanism of ferroptosis and regulate it by some signaling molecules. This review primarily summarized the effects of hydrogen sulfide on ferroptosis and cardiovascular disease, especially its antioxidative stress, and would provide a more effective direction for the clinical study of CVDs.

Ferroptosis is a recently discovered type of cell death caused by the accumulation of iron-dependent lipid peroxides and reactive oxygen species that differs significantly from other cell death pathways such as apoptosis, necrosis, and autophagy. Ferroptosis has an essential role in developing and treating ischemia-reperfusion injury, neurological diseases, cancer, and a variety of other diseases. The ferroptosis mechanism, which can be induced by reagents like erastin and glutamate, and suppressed by antioxidants such as vitamin E and deferoxamine (DFO) chelators, can be regulated at the epigenetic, transcriptional, post-transcriptional, and post-translational levels. Many non-coding RNAs (lncRNA, miRNA, circRNA) that modulate ferroptotic cell death in cancer cells have been determined in a recent study. Furthermore, some anti-cancer drugs (Sorafenib, Sulfasalazine, Acetominofen, Lanperisone, etc.) used in pre-clinical and clinical applications have been shown to induce ferroptosis in various cancer types. However, in addition to the studies in the literature, it is necessary to define novel molecules & non-coding RNAs and determine their effects on the ferroptosis mechanism. Thus, it will be possible to develop effective and safe treatment options.

Bacteria and their enzymatic machinery, also called bacterial cell factories, produce a diverse variety of biopolymers such as polynucleotides, polypeptides and polysaccharides, with different and fundamental cellular functions. Polysaccharides are the most widely used biopolymers, especially in biotechnology. This type of biopolymer, thanks to their physical and chemical properties, can be used to create a wide range of advanced bio-based materials, hybrid materials and nanocomposites for a variety of exciting biomedical applications. In contrast to synthetic polymers, bacterial polysaccharides have several advantages such as biocompatibility, biodegradability, low immunogenicity, non-toxicity, among others. On the other hand, the main advantage of bacterial polysaccharides compared to polymers extracted from other natural sources is that their physicochemical properties such as purity, porosity, malleability, among others, can be adapted to a specific application with the use of biotechnological tools and/or chemical modifications. Another great reason for using bacterial polysaccharides is due to the possibility of developing advanced materials from them using bacterial factories that can metabolize raw materials (recycling of industrial and agricultural wastes) that are readily available and in large quantities. Moreover, through this strategy it is possible to curb environmental pollution. In this article, we project the desire to move towards large-scale production of bacterial polysaccharides taking into account the benefits, weaknesses and prospects in the near future for the development of advanced biological materials for medical and pharmaceutical purposes.

BACKGROUND: Autoimmune diseases are chronic disorders in which the immune system does not recognize and attacks one self's healthy components. In this context, although natural remedies might represent a promising therapeutic strategy, evidence regarding Citrus flavonoids is still controversial. OBJECTIVE: To summarize and critically discuss the clinical evidence on the effects of Citrus flavonoids for the management of autoimmune diseases. METHOD: A systematic review of articles has been carried out independently by two Authors using MEDLINE, Scopus and ISI Web of Science databases. Search terms comprised keywords related to Citrus flavonoids and autoimmune diseases. The last search was performed on March 16, 2021. No language restrictions were applied. Systematic review and study selection were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Before starting the review, Authors defined the types of articles to be included. Three reviewers independently carried out the extraction of papers. RESULTS: Ten clinical studies fulfilled the eligibility criteria and were included in the final review. CONCLUSION: The studies discussed in this review are heterogeneous. Indeed, some studies suggest the use of Citrus flavonoids in the frame of autoimmune disorders, whereas others discourage it. Hence, this systematic review highlights the need of further large-scale clinical studies to define the exact role of Citrus flavonoids in the management of autoimmune diseases (PROSPERO number CRD42021234903).

Microwave radiation is used as a heating source during the synthesis of heterocyclic compounds. The heating mechanisms involved in microwave-induced synthesis include dipolar polarization and ionic conduction. This heating technology follows the green protocol as it involves the use of recyclable organic solvents during synthesis. The microwave heating approach offers a faster rate of reaction, easier work-up procedure, and higher product yield with purity and also reduces environmental pollution. So, microwave heating is applied as a sustainable technology for the efficient production of pyrimidine compounds as one of the heterocyclic moieties. Pyrimidine is a six-membered nitrogenous heterocyclic compound that plays a significant role due to several therapeutic applications. This moiety acts as an essential building block for generating drug candidates with diverse biological activities including anti-cancer (capecitabine), anti-thyroid (propylthiouracil), antihistaminic (pemirolast), antimalarial (pyrimethamine), antidiabetic (alloxan), antihypertensive (minoxidil), anti-inflammatory (octotiamine), antifungal (cyprodinil), antibacterial (sulfamethazine), etc. This review is focused on the synthesis of pyrimidine analogs under microwave irradiation technique and the study of their therapeutic potentials.

Sydnones are among the most well-known mesoionic compounds. Since their synthesis in 1935 by Earl and Mecknay, numerous researches have shown that the chemical behavior, physical and biological properties of sydnones make them among the most useful compounds in organic chemistry. Sydnones undergo thermal 1,3-dipolar cycloaddition reaction with dipolarophiles (alkynes or alkenes) to give exclusively derivatives containing a pyrazole moiety exhibiting numerous applications such as pharmaceuticals and agrochemicals. However, the sydnone cycloaddition reaction with alkynes requires harsh conditions like high temperatures and long reaction times giving poor regioselectivity on the resulting products. To overcome these constraints, new reactions named CuSAC (Copper-Catalyzed Sydnone-Alkyne Cycloaddition) and SPSAC (Strain-Promoted Sydnone-Alkyne Cycloaddition) and have been developed, leading to pyrazoles with interesting constant kinetics.

Chitosan, the only naturally occurring polycationic polysaccharide derived from chitin, has long case been implicated in the designs of nanosystems for diverse biomedical and pharmaceutical applications owing to its exclusive biodegradability, biocompatibility, cationic property and functional groups. Particularly, some intrinsic characteristics of chitosan equip it with high potential for facile preparation, flexible functionalization and modification, which circumvent the defects of chitosan and account for extensive attempts in cancer therapy and theranostic. In this review, we first give a classifiable explanation of strategies in fabricating rationally-designed chitosan-based polymeric nanomaterials for cancer therapy, which are categorized by the physical, chemical and biological intrinsic characteristics of chitosan respectively. Specifically, examples harnessing cationic charge of chitosan are clarified, the accompanied pH-responsive ability functions frequently is also mentioned. Besides, strategies toward the modification of functional groups (amino and hydroxyl groups) in repeated glycosidic units of chitosan and their additional roles are also discussed here. Lastly, The biological superiority of chitosan as an adjuvant or a ligand for glycoprotein and the application of chitosan-based polymeric nanomaterials in theranostic are summarized. Altogether, this review provides a comprehensive overview of recent advances in chitosan-based polymeric nanomaterials for cancer therapy and theranostics from a brand new perspective.

Tyrosine kinase inhibitors (TKIs) are effective drug molecules for the treatment of a various cancers. Nanomedicinal interventions and approaches may not only provide carrying capacities for TKIs but also has the potential to target tumour specific environments and even to cellular compartments. Nano-inspired drug delivery systems may hence enhance the efficacy of the drugs through enhanced tumour-availability resulting in greater efficacy and decreased side effects. A variety of nanosystems have been developed for the delivery of TKIs for the enhanced treatment of cancers, each with their own preparation methods and physicochemical properties. This review will therefore discuss the applicability of nano-interventions towards combination therapies, dose reduction and greater potential treatment outcomes. The individual nanosystems have been highlighted with emphasis given on the developed systems and their efficacy against various cancer cells lines and models.

Neurodegenerative and mental disorders are a public health burden with pharmacological treatments of limited efficacy. Organoselenium compounds are receiving great attention in medicinal chemistry mainly because of their antioxidant and immunomodulatory activities, with a multi-target profile that can favor the treatment of multifactorial diseases. Therefore, the purpose of this review is to discuss recent preclinical studies about organoselenium compounds as therapeutic agents for the management of mental (e.g., depression, anxiety, bipolar disorder, and schizophrenia) and neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis). We have summarized around 70 peer-reviewed articles from 2016 to the present that used in silico, in vitro, and/or in vivo approaches to assess the neuropharmacology of selenium-containing compounds. Among the diversity of organoselenium molecules investigated in the last five years, diaryl diselenides, Ebselen-derivatives, and Se-containing heterocycles are the most representative. Ultimately, this review is expected to provide disease-oriented information regarding the neuropharmacology of organoselenium compounds that can be useful for the design, synthesis, and pharmacological characterization of novel bioactive molecules that can potentially be clinically viable candidates.

P2Y receptors (P2YRs) are G protein-coupled receptors that are activated by extracellular nucleotides. The P2Y6 receptor (P2Y6R) is specifically activated by UDP, causing PKC activation and intracellular calcium ion release through the PLC pathway. Based on receptor tissue distribution and related pathways, several studies have reported that P2Y6R plays a physiological role in mediating inflammation, which suggests that P2Y6R could be a promising molecular target for the treatment of inflammatory diseases. In the past ten years, several P2Y6R antagonists have been discovered as new therapeutic strategies for inflammatory diseases. In this article, we systematically summarize the role of P2Y6R in inflammation and highlight the anti-inflammatory mechanism of a key P2Y6R antagonist, MRS2578. Insight into recent progress on the discovery of P2Y6R antagonists are also discussed.

BACKGROUND: Type-2 diabetes is a chronic progressive metabolic disease resulting in severe vascular complications and mortality risk. Recently, DPP-4 inhibitors are conceived as a favorable class of agents for the treatment of type 2 diabetes due to the minimal side effects. METHODS: Sitagliptin is the first medicine approved for DPP-4 inhibitor. Its structure involved three fragments: 2,4,5-triflorophenyl fragment pharmacophore, enantiomerically β-amino carbonyl linker, and tetrahydrotriazolopyridine. Herein, we are drawn to the possibility of substituting tetrahydrotriazolopyridine motif present in Sitagliptin with a series of new fused pyrazolopyrimidine bicyclic fragment to investigate potency and safety. RESULTS: Two series of fused 6-(aminomethyl)pyrazolopyrimidine and 6-(hydroxymethyl)pyrazolopyrimidine derivatives containing β-amino ester or amide as linkers were successfully designed for the new DPP-4 inhibitors. Most fused 6-methylpyrazolopyrimidines were evaluated against DPP-4 inhibition and selectivity capacity. Based on research study, β-amino carbonyl fused 6-(hydroxymethyl)pyrazolopyrimidine possesses the significant DPP-4 inhibition (IC50 ≤ 59.8 nM) and presents similar with Sitagliptin (IC50 = 28 nM). Particularly, they had satisfactory selectivity over DPP-8 and DPP-9, except for QPP. CONCLUSION: β-Amino esters and amides fused 6-(hydroxymethyl)pyrazolopyrimidine were developed as the new DPP-4 inhibitors. Those compounds with a methyl group or hydrogen in N-1 position and methyl substituted group in C-3 of pyrazolopyrimidine moiety showed better potent DPP-4 inhibition (IC50 = 21.4-59.8 nM). Furthermore, they had satisfactory selectivity over DPP-8 and DPP-9 Finally, the docking results revealed that compound 9n was stabilized at DPP-4 active site and would be a potential lead drug.

BACKGROUND: Last years, nanotechnology-based systems have gained the interest of numerous scientists, especially for biomedical applications. Then, as called, nanocarriers present tunable abilities, can be easily functionalized to target specific epithelial cells, tissues, and organs while various materials can be chosen and generate nanosized particles. At the present, nanoparticles that possess bioadhesion have been studied as potent drug carriers since they can easier penetrate and target organs. OBJECTIVE: Aim of this study was to explore the various applications of the bioadhesive nanoparticles found in the literature. METHOD: Authors have studied the literature finding that bioadhesive nanoparticles can be administered via routes such as oral, topical, ocular, dermal, vaginal, etc according to the clinician's opinion and treatment choice. Therefore, the knowledge of general characteristics of bioadhesive nanoparticles, the bioadhesion theory, and other properties of nanoparticles should be known for the development of innovative bioadhesive drug nanocarriers. RESULTS: In this review article, the authors state the current knowledge of bioadhesion theories. In addition, the present categories of nanoparticles and their basic characteristics are also discussed. Finally, the biomedical applications of bioadhesive nanocarriers and the several administration routes are extensively reviewed. CONCLUSION: The review article aims to cover the most current bioadhesive nanoparticles for drug delivery to assist any scientist who desires to study or develop innovative bioadhesive formulations.

Background- Even though the battle against cancer has advanced remarkably in last few decades and the survival rate has improved very significantly, an ultimate cure for cancer treatment stills remains an undeterred problem. In such scenario, nanoinformatics, which is bioinformatics coupled with nanotechnology, endows with many novel research opportunities in the preclinical and clinical development of specially personalized nanosized drugs and carriers bestowing newer dimensions in anticancer research and therapy. Personalized nanomedicines tends to serve as a promising treatment option for cancer owing to their noninvasiveness and their novel approach. Explicitly, the field of personalized medicine is expected to have an enormous impact in clinical research owing to its diverse advantages and its versatility to adapt a drug to a cohort of patients. Objective- The current review attempts to explain the implications of nanoinformatics as a new emerging field in the field of pharmacogenomics and precision medicine. This review also recapitulates how nanoinformatics could accelerate the developments of personalized nanomedicine in anticancer research, which is undoubtedly the need of the hour. Conclusion- The approach and concept of personalized nanomedicine has been facilitated by humongous impending field of Nanoinformatics. The breakthrough progressions made through nanoinformatics have prominently changed the insight of the future personalized medicinal drug in cancer research. Nanoparticle based medicine has been developing and has created a center of attention in recent years, with a prime focus on proficient delivery mechanisms for various chemotherapy drugs. Nanoinformatics has allowed merging of all recent advances from creating nanosized particles that contain drugs targeting cell surface receptors to other potent molecules designed to kill cancerous cells and its subsequent application to personalize medicine.

Sulfur and oxygen containing-compounds are a relevant class of derivatives that is constantly growing due to their wide range of pharmacological activity, including the antiviral one. As a proof of this, there are several FDA approved antiviral compounds having sulfur and oxygen in their structures. Among RNA viruses, the flavivirus genus (e.g. Dengue, West Nile, Yellow Fever and Zika viruses) holds a relevant place within zoonotic pathogens and thus flavivirus infections are considered a growing risk for the public health. As a consequence, the drug discovery process aimed at identify new anti-flavivirus agents is of great relevance and will help to find effective therapies not available yet. One of the most alarming features of flaviviruses is their ability to co-infect the host, thus aggravating the symptoms of the disease. Therefore, finding compounds endowed with a broad-spectrum anti-flavivirus activity is now becoming a pressing need. In this review, we describe the most promising compounds having both sulfur and oxygen in their structures characterized by a broad-spectrum activity against different flaviviruses. Furthermore, the synthetic procedures applied for the preparation of the described derivatives are also reported. Readers can be inspired by the contents of this review to design and synthesize more effective anti-flavivirus agents as well as to select viral or host targets to achieve an antiviral activity as broad as possible.

BACKGROUND: Mouse Double Minute 2 Homolog (MDM2) oncogenic protein is the principal cellular antagonist of the p53 tumor suppressor gene. Restoration of p53 activity by inhibiting the MDM2-P53 interactions at the molecular level has become the cornerstone of cancer research due to its promising anticancer effects. Natural medicinal products possess various chemical structures and represent an essential source for drug discovery. α-Mangostin (AM) and gambogic acid (G250) are plant-derived compounds that showed inhibitory effects on MDM2-P53 interactions in-vitro and in-vivo. METHODS: Despite the many clinical studies which performed deeper insight about the molecular understanding of the structural mechanisms exhibited by α-Mangostin and Gambogic acid-binding to MDM2 remains critical. In this study, comparative molecular dynamics simulations were performed for each Apo and bound p53 and MDM2 proteins to shed light on the MDM2-p53 interactions and get a better understanding of the inhibition mechanisms. RESULTS: Results revealed atomistic interaction of AM and G250 within the MDM2-p53 interaction cleft. Both compounds mediate the interaction between the α-helix motifs of the p53 amino-terminal domain. Which caused a significant separation between orthogonally opposed residues, specifically Lys8 and Gly47 residues of the p53 and MDM2, respectively. Contrasting changes in magnitudes were observed in per-residue fluctuation on AM and G250 (~0.04 nm and ~2.3 nm, respectively). The Radius of gyration (~0.03 nm and 0.04 nm, respectively), C-alpha deviations (~0.06 nm and 0.1 nm, respectively). The phenolic group of AM was found to establish hydrogen interactions with Glu28 and His96 residues of MDM2. The trioxahexacyclo-ring of G250 also forms hydrogen bond interactions with Lys51 and Leu26 residues of MDM2. CONCLUSION: Utilizing the information provided on the inhibitory binding mode adopted by each compound in this study may further assist in the tailored designs for cancer therapeutics.