Mediated Synthesis Research Articles

Pharmaconutraceutical Chondroguard®TRIO – chondroprotector with immunomodulatory activity

Understanding the major pathological pathways and the key molecules involved in the pathogenesis of inflammatory processes in joints, particularly in osteoarthritis (OA), is crucial for drug and pharmaconutraceuticals development. OA is a degenerative joint disease that predominantly affects articular cartilage. Destruction of hyaline cartilage and restructuring of subchondral bone are accompanied by synovial inflammation in the joint, including the facet joint of the spine, manifested by pain in the joint, low back pain (LBP), and limitation of functional activity. The article discusses the relationship between immune and inflammatory mechanisms in OA of any location, including the joints of the spine. One of the mechanisms for the formation of a “vicious circle of inflammation” during the activation of discoidin receptors by endogenous type II collagen is discussed, leading to the induction of the synthesis of pro-inflammatory mediators: tumor necrosis factor α(TNFα), metalloproteinases (MMPs) 1 and 13, interleukins (IL) 1 and 6. Inflammation, in turn, leads to a decrease in the synthesis and destruction of endogenous type II collagen and, subsequently, to cartilage destruction. Cartilage fragments entering the joint space of the intercellular matrix enhance the synthesis of TNFα, IL, and MMP and exacerbate the inflammatory process. Oral ingestion of exogenous undenatured type II collagen(NK-II) helps, first, to inactivate the binding of fragments of destroyed endogenous type II collagen to discoidin receptors and to break the "vicious circle of inflammation"; secondly, through the mechanism of oral/intestinal tolerance via the lymphoid system in Peyer's patches of the small intestine, leads to the activation of immune cells (T-lymphocytes) and initiation of the immune response – the synthesis of anti-inflammatory mediators (transforming growth factor β, IL4 and IL10). The new pharmaconutraceutical Chondroguard®TRIO, which contains chondroprotectors (chondroitin sulfate and glucosamine sulfate) as well as NK-II, will make it possible to influence the key sites of the pathological process in OA.

N-Ylide Mediated Synthesis and Resolution of a Chiral Pyrimidinyl Cyclopropane Carboxylic Acid

N-Ylide Mediated Synthesis and Resolution of a Chiral Pyrimidinyl Cyclopropane Carboxylic Acid

Stabilization of activated mast cells by ORAI1 inhibitor suppresses peanut-induced anaphylaxis and acute diarrhea

Mast cell (MC) activation triggered by immunoglobulin E (IgE)-antigen crosslinking involves intracellular Ca2+ influx through the ORAI1 channel, which precedes granule exteriorization and de novo synthesis of mediators. Pharmacologically suppressing MCs via the inhibition of the ORAI1 Ca2+ channel may represent a potential strategy for preventing anaphylaxis. This study demonstrated that peanut-induced anaphylaxis in sensitized mice resulted in significant hypothermia and acute diarrhea. Utilizing the Mcpt5cre-DTA mouse model, we demonstrated that this anaphylactic response was mediated by IgE-antigen-induced MC activation. Prophylactic administration of MC suppressors was an effective means of preventing peanut-induced anaphylaxis. In addition, we observed the potent efficacy of an ORAI1 inhibitor in suppressing the FcεRI-mediated response of murine or human MCs, even when administered concurrently or post-allergen exposure. Mechanistically, the ORAI1 inhibitor was found to prevent the association of Synaptotagmin-2 with the SNARE complex. In an in vivo mouse model of peanut-induced anaphylaxis, the administration of the ORAI1 inhibitor after allergen challenge effectively suppressed allergic acute diarrhea and ameliorated anaphylaxis. Therefore, pharmacological intervention of ORAI1 channel inhibition in MCs represents a promising therapeutic avenue for the treatment of peanut-induced anaphylaxis and acute diarrhea in vivo.

Phytochemical Substances—Mediated Synthesis of Zinc Oxide Nanoparticles (ZnO NPS)

Artemisia absinthium (A. absinthium) leaf extract was successfully used to create zinc oxide nanoparticles (ZnO NPs), and their properties were investigated via several techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), Fourier transform infrared (FTIR), and ultraviolet–visible spectroscopy (UV–Vis spectroscopy). SEM analysis confirmed the spherical and elliptical shapes of the particles. Three different zinc peaks were observed via EDX at the energies of 1, 8.7, and 9.8 keV, together with a single oxygen peak at 0.5 keV. The XRD analysis identified ZnO NPs as having a hexagonal wurtzite structure, with a particle size that decreased from 24.39 to 18.77 nm, and with an increasing surface area (BET) from 4.003 to 6.032 m2/g for the ZnO (without extract) and green ZnO NPs, respectively. The FTIR analysis confirmed the groups of molecules that were accountable for the stabilization and minimization of the ZnO NPs, which were apparent at 3400 cm. Using UV–Vis spectroscopy, the band-gap energies (Egs) for the green ZnO and ZnO (without extract) NPs were estimated, and the values were 2.65 and 2.79 eV, respectively.

Integrated transcriptome and miRNA sequencing analyses reveal that hypoxia stress induces immune and metabolic disorders in gill of genetically improved farmed tilapia (GIFT, Oreochromis niloticus).

The survival and growth of fish are significantly impacted by a hypoxic environment (low dissolved oxygen). In this study, we compared tissue structure, physiological changes, and mRNA/miRNA transcriptome, in gills of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) between the hypoxic group (DO: 0.55mg/L, HG) and the control group (DO: 5mg/L, CG). The results showed that the gill filaments in the hypoxic group showed curling, engorgement, and apoptotic cells increased, and that exposure for 96h resulted in a reduction in the antioxidant capacity. We constructed and sequenced miRNA and mRNA libraries from gill tissues of GIFT at 96h of hypoxia stress. Between the HG and CG, a total of 14 differentially expressed (DE) miRNAs and 1557 DE genes were obtained. GO and KEGG enrichment showed that DE genes were mainly enriched in immune and metabolic pathways such as natural killer cell mediated cytotoxicity, steroid biosynthesis, primary immunodeficiency, and synthesis and degradation of ketone bodies. Based on the results of mRNA sequencing and screening for miRNA-mRNA pairs, we selected and verified six DE miRNAs and their probable target genes. The sequencing results were consistent with the qRT-PCR validation results. The result showed that under hypoxia stress, the innate immune response was up-regulated, and the adaptive immune response was down-regulated in the gill of GIFT. The synthesis of cholesterol in gill cells is reduced, which is conducive to the absorption of solvent oxygen. These findings offer fresh information about the processes of fish adaptation to hypoxic stress.

Marine Actinobacterial Streptomyces Sp., Mediated Synthesis of Silver Nanoparticles: Characterization and Different Biological Properties Under In-vitro Condition

Background: Green synthesis of nanomaterials is promising as a biological source for treating different diseases without side effects. Methods: In the present study, marine Streptomyces sp. was used to biosynthesize silver nanoparticles, which were then characterized and evaluated for various therapeutic activities and A 549 breast cancer cell line for cytotoxic evaluation. Results: The Surface Plasmon Resonance exhibited a peak at 434 nm, and the FT-IR spectrum of St- AgNPs revealed the presence of secondary metabolites, which were used for stabilization and capping processes. The St-AgNPs showed an agglomerated spherical shape with a diameter of 10–35 nm. The elemental composition was silver (60.0%), oxygen (14.9%), sodium (14.9%), and carbon (15.0%). The St-AgNPs exhibited significant antioxidant activity in terms of DPPH 62.2 ± 2.1, H2O2 57.76 ± 2.4%, TAA 64.3±2.7, and NO 64.3 ± 2.7 at 100 μg/mL. The cytotoxic activity using A 549 Breast cancer cell line was found to be only 20 % of viable cells at 100 μg concentration. St-AgNPs revealed good antibacterial efficacy against Streptococcus mutants, Klebsiella Sp. and Staphylococcus aureus (MRSA). Conclusion:: The St-AgNPs may be a good choice for antibacterial, antioxidant and cytotoxic agents in the future with further relevant study and may be used in the field of nano biomedicine.

Dietary Implications of Polyunsaturated Fatty Acids during Pregnancy and in Neonates.

Certain limitations exist for animals to modify fatty acid changes. Besides the role of arachidonic acid (AA), docosahexaenoic acid (DHA) and other 20-carbon long-chain polyunsaturated fatty acids (LCPUFAs) for the synthesis of inflammatory mediators as eicosanoids, different LCPUFAs have many other effects, including their abilities to regulate gene expression and downstream events. LCPUFAs are susceptible to autoxidation, which is prevented by the action of antioxidants in the form of enzymes like superoxide dismutases, catalases and peroxidases, as well as antioxidant compounds that protect against oxidation or repair the damage caused. Under normal conditions, the fetus needs both essential fatty acids (EFAs) and LCPUFAs, which are obtained from its mother by placental transfer. In early pregnancy, dietary derived fatty acids are accumulated in maternal adipose tissue. However, during late pregnancy, corresponding to the period of the highest fetal growth, maternal adipose tissue becomes catabolic and LCPUFAs are released into the circulation by adipose lipolytic activity. The released LCPUFAs are taken up by maternal liver to be esterified and released back to the circulation as triacylglycerides (TAGs) in very-low-density lipoprotein (VLDL) that become available to the placenta to be transferred to the fetus in the form of non-esterified fatty acids (NEFAs). An enhanced adipose tissue lipolysis is maintained around parturition and esterified LCPUFAs are diverted to mammary glands thanks to an increased activity of lipoprotein lipase for milk production. Throughout this process, LCPUFAs become available to the newborn during suckling. The important role of both DHA and AA for the development of the nervous system and for growth has motivated their dietary supplement during different postnatal stages. This has been especially important in preterm infants both because under normal conditions, the fetus acquires most of these fatty acids during late pregnancy, and because the immaturity of the enzyme systems for the synthesis of AA and DHA from their respective EFAs.

Hypervalent Iodine Mediated Synthesis of Sulfinamidines from Sulfenamides.

In this study, we present a novel, efficient method for the oxidative amination of sulfenamides using diacetoxyiodobenzene (PhI(OAc)2) and amines under basic conditions. This innovative technique streamlines the synthesis of sulfinamidines under mild, metal-free conditions, achieving outstanding yields of up to 99%. Furthermore, we propose possible pathways that elucidate the observed molecular sequence of events in this reaction. This cutting-edge approach not only advances the synthesis of valuable sulfinamidine compounds but also expands the synthetic toolbox available to chemists, paving the way for future discoveries in organic synthesis and potential applications in medicinal chemistry.

S1P/S1PR signaling pathway advancements in autoimmune diseases.

Sphingosine-1-phosphate (S1P) is a versatile sphingolipid that is generated through the phosphorylation of sphingosine by sphingosine kinase (SPHK). S1P exerts its functional effects by binding to the G protein-coupled S1P receptor (S1PR). This lipid mediator plays a pivotal role in various cellular activities. The S1P/S1PR signaling pathway is implicated in the pathogenesis of immune-mediated diseases, significantly contributing to the functioning of the immune system. It plays a crucial role in diverse physiological and pathophysiological processes, including cell survival, proliferation, migration, immune cell recruitment, synthesis of inflammatory mediators, and the formation of lymphatic and blood vessels. However, the full extent of the involvement of this signaling pathway in the development of autoimmune diseases remains to be fully elucidated. Therefore, this study aims to comprehensively review recent research on the S1P/S1PR axis in diseases related to autoimmunity.

MSC therapy ameliorates experimental gouty arthritis hinting an early COX-2 induction.

The specific effect of Adipose-Derived Mesenchymal Stem Cells (Ad-MSC) on acute joint inflammation, where the response mostly depends on innate immunity activation, remains elusive. The pathogenesis of gouty arthritis, characterized by the deposition of monosodium urate (MSU) crystals in the joints, associated to acute flares, has been associated to NLRP3 inflammasome activation and subsequent amplification of the inflammatory response. Our aim was to study the effect of human Ad-MSC administration in the clinical inflammatory response of rabbits after MSU injection, and the molecular mechanisms involved. Ad-MSC were administered by intraarterial route shortly after intraarticular MSU crystal injections. Joint and systemic inflammation was sequentially studied, and the mechanisms involved in NLRP3 inflammasome activation, and the synthesis of inflammatory mediators were assessed in the synovial membranes 72h after insult. Ad-MSC and THP-1-derived macrophages stimulated with MSU were co-cultured in transwell system. A single systemic dose of Ad-MSC accelerated the resolution of local and systemic inflammatory response. In the synovial membrane, Ad-MSC promoted alternatively M2 macrophage presence, inhibiting NLRP3 inflammasome and inducing the production of anti-inflammatory cytokines, such as IL-10 or TGF-β, and decreasing nuclear factor-κB activity. Ad-MSC induced a net anti-inflammatory balance in MSU-stimulated THP-1 cells, with a higher increase in IL-10 and IDO expression than that observed for IL-1β and TNF. Our in vivo and in vitro results showed that a single systemic dose of Ad-MSC decrease the intensity and duration of the inflammatory response by an early local COX-2 upregulation and PGE2 release. Ad-MSCs suppressed NF-kB activity, NLRP3 inflammasome, and promoted the presence of M2 alternative macrophages in the synovium. Therefore, this therapeutic approach could be considered as a pharmacological alternative in patients with comorbidities that preclude conventional treatment.

Propylphosphonic Anhydride (T3P®)‐ Mediated Efficient Synthesis of Substituted 2‐Amino Phenoxazinones

AbstractAn efficient synthesis of substituted 2‐amino phenoxazinones was described using T3P® via oxidative cross coupling of commercially available 2‐amino phenols. The synthesis is a transition metal free, enzyme free and a non‐photo chemical reaction involving shorter reaction times with moderate to good yields.

Agaricus Bisporus Mediated Synthesis of Cobalt Ferrite, Copper Ferrite and Zinc Ferrite Nanoparticles for Hyperthermia Treatment and Drug Delivery

Agaricus Bisporus Mediated Synthesis of Cobalt Ferrite, Copper Ferrite and Zinc Ferrite Nanoparticles for Hyperthermia Treatment and Drug Delivery

Eucalyptus globulus Mediated Green Synthesis of Environmentally Benign Metal Based Nanostructures: A Review.

The progress in nanotechnology has effectively tackled and overcome numerous global issues, including climate change, environmental contamination, and various lethal diseases. The nanostructures being a vital part of nanotechnology have been synthesized employing different physicochemical methods. However, these methods are expensive, polluting, eco-unfriendly, and produce toxic byproducts. Green chemistry having exceptional attributes, such as cost-effectiveness, non-toxicity, higher stability, environment friendliness, ability to control size and shape, and superior performance, has emerged as a promising alternative to address the drawbacks of conventional approaches. Plant extracts are recognized as the best option for the biosynthesis of nanoparticles due to adherence to the environmentally benign route and sustainability agenda 2030 of the United Nations. In recent decades, phytosynthesized nanoparticles have gained much attention for different scientific applications. Eucalyptus globulus (blue gum) is an evergreen plant belonging to the family Myrtaceae, which is the targeted point of this review article. Herein, we mainly focus on the fabrication of nanoparticles, such as zinc oxide, copper oxide, iron oxide, lanthanum oxide, titanium dioxide, magnesium oxide, lead oxide, nickel oxide, gold, silver, and zirconium oxide, by utilizing Eucalyptus globulus extract and its essential oils. This review article aims to provide an overview of the synthesis, characterization results, and biomedical applications of nanoparticles synthesized using Eucalyptus globulus. The present study will be a better contribution to the readers and the students of environmental research.

Influence of titanium and zirconia substrates on the synthesis of inflammatory mediators.

The repair and homeostasis of peri-implant tissues depend on several factors such as the local presence of pathogenic bacteria and their products. Among other events, peri-implant tissue response is also related to the implant material used, which interferes with cells and extracellular matrix interactions, affecting the osseointegration process. In this study, the influence of zirconia (Zr) and titanium (Ti) substrates on the response of preosteoblasts (MC3T3) and murine macrophages (RAW 264.7) exposed to lipopolysaccharide (LPS, P. gingivalis) was evaluated. Zr and Ti disks were obtained and subjected to surface roughness standardization, which was analyzed by scanning electronic microscopy (SEM). The cells were subsequently cultured on Zr and Ti surfaces in AlphaMEM culture medium for 24 h, followed by LPS stimulus for 4 h. The production of reactive oxygen species (ROS) and gene expression of inflammatory markers were determined. SEM images showed that Ti disks exhibited higher surface roughness than that of Zr disks. Cells that seeded onto Ti and Zr had increased expression of inflammatory mediators and ROS production in the presence of LPS; however, such cell responses were more evident for Ti disks. These data indicate that contact of cells with Zr surfaces may lead to a lower inflammatory potential than Ti surfaces. Elucidation of the inflammatory response triggered by LPS for cells in contact with titanium and zirconia may contribute to the selection of materials for installation of osseointegrated implants.

Polyunsaturated Fatty Acids And Lipid Mediators Controlling Chronic Inflammation In Asthma

Asthma is a common chronic heterogeneous inflammatory respiratory disease with complex pathogenesis. Chronic lung inflammation can be the result of a defect in the resolution of the inflammatory process caused by an imbalance between the synthesis of proinflammatory and pro-resolving lipid mediators. The identification of immunomodulatory effects of eicosanoids, specialized pro-resolving mediators (SPMs), and endocannabinoids synthesized from polyunsaturated fatty acids (PUFAs) allows taking a fresh look at the ways of controlling inflammation rather than solely at its mechanisms. The use of ω-3 PUFA-containing food supplements in combination with standard therapy leads to improved asthma control due to the ability of ω-3 PUFAs to stimulate SPM synthesis and inhibit intracellular signaling pathways of inflammation. Lipid mediators are agonists of peroxisome proliferator-activated receptors (PPARs) and glucocorticoid receptors (GR) that have anti-inflammatory properties. The receptors that are widely expressed in the pulmonary epithelium, endothelium, dendritic cells, eosinophils, fibroblasts, and macrophages play an important role in the regulation of immunometabolic homeostasis in the bronchopulmonary system. Our review systematizes the published data on the properties and mechanism of action of biologically active ω-3 and ω-6 PUFAs involved in the inflammatory process in asthma. Also, this article presents the prospects of using ω-3 PUFAs for the resolution of inflammation in asthma.

Quantum Tunneling Mediated Low-Temperature Synthesis of Interstellar Hemiacetals.

Sugars and sugar-related molecules are ubiquitous in carbonaceous meteorites and in star-forming regions, but the underlying mechanisms of their formation have remained largely elusive. Herein, we report an unconventional synthesis of the hemiacetal, (R/S)-1-methoxyethanol (CH3OCH(OH)CH3), through quantum tunneling mediated reactions in low-temperature interstellar model ices composed of acetaldehyde (CH3CHO) and methanol (CH3OH). The detection of racemic 1-methoxyethanol through a bottom-up synthesis from simple, abundant precursor molecules within interstellar ices represents a vital starting point to the formation of complex interstellar hemiacetals. Once synthesized, hemiacetals may act as possible precursors to interstellar sugars and sugar-related molecules in deep space.

Eggshell Membrane Mediated Synthesis of CdO–NiO Nanocomposite for Multifunctional Applications

Eggshell Membrane Mediated Synthesis of CdO–NiO Nanocomposite for Multifunctional Applications

Schisandrin A ameliorates airway inflammation in model of asthma by attenuating Th2 response

Asthma is a persistent respiratory ailment that displays periodicity and is linked to the equilibrium of T cells. Several compounds obtained from Chinese herbal medicines display beneficial impacts on T cell regulation and the attenuation of inflammatory mediator synthesis. Schisandrin A, an active lignan derived from the Schisandra fruit, exhibits anti-inflammatory characteristics. In the present study, the network analysis conducted revealed that the nuclear factor-kappaB (NF-κB) signaling pathway is likely a prominent contributor to the anti-asthmatic effects of schisandrin A. In addition, it has been established that the inhibition of cyclooxygenase 2 (COX-2/PTGS2) is likely a significant factor in this process. The results of in vitro experiments have substantiated that schisandrin A can effectively lower the expression of COX-2 and inducible nitric oxide synthase (iNOS) in 16 HBE cells and RAW264.7 cells in a manner that is dependent on the dosage administered. It was able to effectively reduce the activation of the NF-κB signaling pathway while simultaneously improving the injury to the epithelial barrier function. Furthermore, an investigation utilizing immune infiltration as a metric revealed an inequity in Th1/Th2 cells and a surge in Th2 cytokines in asthma patients. In the OVA-induced asthma mice model, it was observed that schisandrin A treatment effectively suppressed inflammatory cell infiltration, reduced the Th2 cell ratio, inhibited mucus secretion, and prevented airway remodeling. To summarize, the administration of schisandrin A has been found to effectively alleviate the symptoms of asthma by impeding the production of inflammation, which includes reducing the Th2 cell ratio and improving the integrity of the epithelial barrier function. These findings offer valuable insights into the potential therapeutic applications of schisandrin A for the treatment of asthma.

Rutin Mediated Synthesis of Silver Nanoparticles derived from Melia dubia and Evaluation of Antioxidant and Antimicrobial Activity

Researches based on bio inspired synthesis of noble metal nano materials has become a promising one in today’s biomedical approach in therapy and diagnosis due to multidimensional applications. Furthermore, silver nanoparticles were reported to have several medicinal applications. Hence the present study was to explore the antioxidant and antimicrobial efficacy of silver nanoparticles (AgNPs) synthesized from rutin isolated from the methanolic extract of leaves of Melia dubia. The biosynthesized nanoparticles were analyzed using UV-Visible, FT-IR, XRD and SEM techniques. The band at 398.5nm in the UV-Visible spectra confirmed the formation of AgNPs. The characteristic shift in OH and C=O peak after the formation of silver nano particles shows the participation of biomaterial (Rutin) in the reduction process which is further supported by SEM report. The average size of the particle (19 nm) was determined from XRD analysis using the Scherrer’s equation. The antimicrobial and antioxidant efficacy of harvested nanoparticles were compared for their potential with rutin and silver salt. The synthesized material was shown to have good antimicrobial activity towards the tested bacteria and fungi and potentially active towards free radicals. Thus, the silver nanoparticles (AgNps) synthesized using bio-flavanoid viz. rutin are potentially good and therefore can be further studied for pharmacological activities.

Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors' previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli via synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1β and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.