Oleoresin Capsicum (OC) Spray: An Assessment of Respiratory Health and its Management Following Accidental and Deliberate Exposures.

Introduced into law enforcement in 1976, the oleoresin capsicum (OC) spray has been labeled as one of the most significant and radical developments in law enforcement. However, epidemiological research on OC health effects is deficient, receiving little public support. The major responses to acute exposure to OC spray can be found in the pulmonary system. The molecular mechanism(s) involved in the action of capsaicinoids, the active constituents in OC, are complex cascades of reactions which end up in necrosis or apoptosis. OC may also damage and deplete biological redox systems in the epithelial lining fluids and within cells and mitochondria, modifying structural proteins and nucleic acids and leading to enzyme inactivation. Since there are no characteristic laboratory tests available for identification or confirmation of OC exposure, and on the basis of prevailing data, reassessment of the health risks of OC exposures in vulnerable populations and in-depth study of the molecular mechanics of receptors is the need of the hour for the development of effective countermeasures. This review aims to consider evidence for adverse effects of OC spray used in ways comparable to their application by law enforcement personnel and civilians, with possible treatment recommendations that are precedent for improved management.

Novel fibrous Ag(NP) decorated clay-polymer composite: Implications in water purification contaminated with predominant micro-pollutants and bacteria.

Due to the potential harm caused by emerging micro-pollutants to living organisms, contaminating water supplies by micro-pollutants like EDCs, pharmaceuticals, and microorganisms has become a concern in many countries. Considering both microbiological and micro-pollutant exposure risks associated with water use for agricultural/or household purposes, it is imperative to create a strategy for improving pollutant removal from treated wastewater that is both effective and affordable. Natural clay minerals efficiently remove contaminants from wastewater, though the pristine clay has less affinity to several organic pollutants. Hydrophilic polymers, viz., poly(ethylene glycol) (PEG), improve the dispersion of particles, flocculation processes, and surface properties. In this study, PEG grafted with attapulgite, thereby providing a high-specific surface-area, mesoporous materials for the adsorption of micro-pollutants like ciprofloxacin (CIP) and 17α-ethinylestradiol (EE2) at high rates. A gentle washing process regenerates the clay-polymer material several times with no performance loss, and the natural water implications show fair applicability of solid in decontaminating the CIP and EE2 in an aqueous medium. Further, greenly synthesized silver nanoparticles in situ disperse with the clay polymer efficiently remove the gram-positive and gram-negative bacterium viz., Bacillus subtilis, and Pseudomonas aeruginosa, which are commonly persistent in aquatic environments. The clay polymer outperformed a modified clay composite to eliminate microorganisms and organic micro-pollutants in significant quantities quickly. These results clearly show the importance of fibrous clay-polymer composite for water purification technologies.

Optimization and establishment of laboratory rearing conditions for Cimex lectularius L. against variable temperature and relative humidity.

Emerging infestations of bed bugs are affecting normal human lifestyle globally. This study has been designed to optimize the rearing conditions for Cimex lectularius L. (Hemiptera), to support the scientific research on them. Bed bugs have been projected onto three different temperature (20 °C, 25 °C, and 30 °C) and relative humidity (50%, 70%, and 90%) conditions to check their overall growth and survival rate. Adult mortality, weight loss, egg laying, percentage hatching, hatching initiation and completion, nymph mortality, and molting have been evaluated to optimize the best conditions. The temperature at 25 °C with 90% RH showed minimum mortality for adults (female 13.33 ± 3.33% and male 6.67 ± 3.33%) and nymphs (13.33 ± 3.33%), while maximum egg laying (40.33 ± 1.86), with highest percentage hatching (98.23 ± 0.58%). At 30 °C with 90% RH, hatching initiation and completion (5.19 ± 0.12 days and 7.23 ± 0.16 days) as well as molting initiation and completion (3.73 ± 0.12 days and 7.00 ± 0.24 days) were found to be fastest. Thus, it can be concluded that 25 °C with 90% RH is ideal for rearing of adults and 30 °C with 90% RH is appropriate for rapid growth of nymphs.

Role of biomarkers and molecular signaling pathways in acute lung injury.

BACKGROUND: Acute lung injury (ALI) is caused by bacterial, fungal, and viral infections. When pathogens invade the lungs, the immune system responds by producing cytokines, chemokines, and interferons to promote the infiltration of phagocytic cells, which are essential for pathogen clearance. Their excess production causes an overactive immune response and a pathological hyper-inflammatory state, which leads to ALI. Until now, there is no particular pharmaceutical treatment available for ALI despite known inflammatory mediators like neutrophil extracellular traps (NETs) and reactive oxygen species (ROS). OBJECTIVES: Therefore, the primary objective of this review is to provide the clear overview on the mechanisms controlling NETs, ROS formation, and other relevant processes during the pathogenesis of ALI. In addition, we have discussed the significance of epithelial and endothelial damage indicators and several molecular signaling pathways associated with ALI. METHODS: The literature review was done from Web of Science, Scopus, PubMed, and Google Scholar for ALI, NETs, ROS, inflammation, biomarkers, Toll- and nucleotide-binding oligomerization domain (NOD)-like receptors, alveolar damage, pro-inflammatory cytokines, and epithelial/endothelial damage alone or in combination. RESULTS: This review summarized the main clinical signs of ALI, including the regulation and distinct function of epithelial and endothelial biomarkers, NETs, ROS, and pattern recognition receptors (PRRs). CONCLUSION: However, no particular drugs including vaccine for ALI has been established. Furthermore, there is a lack of validated diagnostic tools and a poor predictive rationality of current therapeutic biomarkers. Hence, extensive and precise research is required to speed up the process of drug testing and development by the application of artificial intelligence technologies, structure-based drug design, in-silico approaches, and drug repurposing.

Obesity-associated Airway Hyperresponsiveness: Mechanisms Underlying Inflammatory Markers and Possible Pharmacological Interventions.

Obesity is rapidly becoming a global health problem affecting about 13% of the world's population affecting women and children the most. Recent studies have stated that obese asthmatic subjects suffer from an increased risk of asthma, encounter severe symptoms, respond poorly to anti-asthmatic drugs, and ultimately their quality-of-life decreases. Although, the association between airway hyperresponsiveness (AHR) and obesity is a growing concern among the public due to lifestyle and environmental etiologies, however, the precise mechanism underlying this association is yet to establish. Apart from aiming at the conventional antiasthmatic targets, treatment should be directed towards ameliorating obesity pathogenesis too. Understanding the pathogenesis underlying the association between obesity and AHR is limited, however, a plethora of obesity pathologies have been reported viz., increased pro-inflammatory and decreased anti-inflammatory adipokines, depletion of ROS controller Nrf2/HO-1 axis, NLRP3 associated macrophage polarization, hypertrophy of WAT, and down-regulation of UCP1 in BAT following down-regulated AMPKα and melanocortin pathway that may be correlated with AHR. Increased waist circumference (WC) or central obesity was thought to be related to severe AHR, however, some recent reports suggest body mass index (BMI), not WC tends to exaggerate airway closure in AHR due to some unknown mechanisms. This review aims to co-relate the above-mentioned mechanisms that may explain the copious relation underlying obesity and AHR with the help of published reports. A proper understanding of these mechanisms discussed in this review will ensure an appropriate treatment plan for patients through advanced pharmacological interventions.

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review.

Currently, corneal blindness is affecting >10 million individuals worldwide, and there is a significant unmet medical need because only 1.5% of transplantation needs are met globally due to a lack of high-quality grafts. In light of this global health disaster, researchers are developing corneal substitutes that can resemble the human cornea in vivo and replace human donor tissue. Thus, this review examines ROCK (Rho-associated coiled-coil containing protein kinases) inhibitors as a potential corneal wound-healing (CWH) therapy by reviewing the existing clinical and nonclinical findings. The systematic review was done from PubMed, Scopus, Web of Science, and Google Scholar for CWH, corneal injury, corneal endothelial wound healing, ROCK inhibitors, Fasudil, Netarsudil, Ripasudil, Y-27632, clinical trial, clinical study, case series, case reports, preclinical study, in vivo, and in vitro studies. After removing duplicates, all downloaded articles were examined. The literature search included the data till January 2023. This review summarized the results of ROCK inhibitors in clinical and preclinical trials. In a clinical trial, various ROCK inhibitors improved CWH in individuals with open-angle glaucoma, cataract, iris cyst, ocular hypertension, and other ocular diseases. ROCK inhibitors also improved ocular wound healing by increasing cell adhesion, migration, and proliferation in vitro and in vivo. ROCK inhibitors have antifibrotic, antiangiogenic, anti-inflammatory, and antiapoptotic characteristics in CWH, according to the existing research. ROCK inhibitors were effective topical treatments for corneal infections. Ripasudil, Y-27632, H-1152, Y-39983, and AMA0526 are a few new ROCK inhibitors that may help CWH and replace human donor tissue.

Polycyclic aromatic hydrocarbon (PAH) remediation during vermicomposting and composting: Mechanistic insights through PAH-budgeting.

Knowledge on the mechanism of earthworm-induced removal of polycyclic aromatic hydrocarbons (PAH) in vermicomposting systems and interaction with nutrient mineralization and microbial growth is scarce in literature. Moreover, the PAH accumulation capacity of Eudrilus eugeniae has not been studied. This research, therefore, investigates the apportionment dynamics of 13 PAH compounds in aerobic composting and vermicomposting (Eisenia fetida and E. eugeniae) systems using novel budget equations. The PAH removal efficiency of vermicomposting was significantly higher (2-threefold) than composting with concurrent microbial augmentation (p < 0.01). However, the 4-6 ring compounds reduced more significantly (30-50%) than the 3-ring PAHs (p < 0.01), and E. eugeniae was an equally competitive PAH-accumulator compared to E. fetida. The budget equations revealed that although the bioaccumulation capabilities of earthworms were retarded due to PAH exposure, earthworms facilitated PAH-immobilization in decomposed feedstock. A marked increase in bacterial, fungal, and actinomycetes proliferation in PAH-spiked vermibeds with parallel removal of the PAHs indicated that earthworm-induced microbial enrichment plays a vital role in PAH detoxification during vermicomposting. Correlation analyses strongly implied that earthworm-driven mineralization-humification balancing and microbial enrichment could be the critical mechanism of PAH remediation under vermicomposting.

Investigating the effects of dermal exposure to in-vivo animal models on the riot-control properties of a powder formulation of Tragia involucrata leaf hair lining.

Purpose: Riot control agents (RCAs) such as CS, CN, CR, PAVA, and OC, etc., are already in use and has produced numerous health risks, including skin burns, dermatitis, gastrointestinal issues, impairment of respiratory variables, conjunctivitis, etc., and even prolonged and repeated exposure may cause death. Therefore, there is a demand and need for non-lethal, non-toxic RCAs that can effectively control riots without resulting in fatal outcomes. This study was carried out to evaluate the health risks related to a novel formulation made from isolated Tragia involucrata leaf hair lining, that can be used as the best suitable non-lethal RCAs.Methods: According to the OECD guidelines, studies on acute dermal toxicity, dermal irritation/corrosion, and skin sensitisation were carried out. Wistar rats were used in an acute dermal toxicity study, and the results indicated no mortality, morbidity, or abnormal food-and-water intake, biochemical parameters, or histopathological examination findings. A study on dermal irritation in Rabbits produced moderate erythema and the effect was instantaneous and resolved within 72 hrs of post-exposure. A skin sensitisation test was conducted on Guinea pig.Results: The results showed that the formulation had moderate skin-sensitizing properties after the application of the challenge dose. Patchy erythema was seen, and it went away 30 hrs after the gauze patch was removed.Conclusion: The preclinical results did not produce any indication of severe toxicity which supports it to be used as a natural RCAs in the future.

Toxicological evaluation of a nonlethal riot control combinational formulation upon dermal application using animal models.

Numerous adverse effects on human health have been reported in epidemiological studies of oleoresin capsicum (OC) and other riot control agents (RCAs). Importantly, the daunting risk of such RCAs can be neutralized by optimizing the desired concentration of such agents for mob dispersal. Hence, a nonlethal riot control combinational formulation (NCF) was prepared for dispersing rioters without imparting fatal outcomes. However, for desired utilization of NCF, it is essential to recognize its extent of potential toxicity. Therefore, the current investigation evaluated the dermal toxicity of NCF using experimental animals in compliance with the OECD guidelines. Additionally, few essential metal ions were analyzed and found non -significantly different in the test rats as compared to control rats. Moreover, abnormal dermal morphology and lesions ultrastructural tissue defects were not noticed as evinced by different studies like ultrasonography, histology, and scanning electron microscopy (SEM) respectively. Further, Doppler ultrasonography exhibited non-significantly different blood flow velocity in both groups, whereas miles test demonstrated a significantly increased Evans blue concentration in test rats compared to the control rats, which might be due to an initial increase in blood flow via an instant action of the NCF at the cutaneous sensory nerve endings. However, our results demonstrated NCF can produce initial skin irritating and sensitizing effects in guinea pigs and rabbits without the antecedence of acute toxicity (≤2000 mg/kg) in Wistar rats.

Transient Receptor Potential Vanilloid (TRPV4) channel inhibition: A novel promising approach for the treatment of lung diseases.

Research on transient receptor potential vanilloid-4 (TRPV4) can provide a promising potential therapeutic target in the development of novel medicines for lung disorders. TRPV4 expresses in lung tissue and plays an important role in the maintenance of respiratory homeostatic function. TRPV4 is upregulated in life-threatening respiratory diseases like pulmonary hypertension, asthma, cystic fibrosis, and chronic obstructive pulmonary diseases. TRPV4 is linked to several proteins that have physiological functions and are sensitive to a wide variety of stimuli, such as mechanical stimulation, changes in temperature, and hypotonicity, and responds to a variety of proteins and lipid mediators, including anandamide (AA), the arachidonic acid metabolite, 5,6-epoxyeicosatrienoic acid (5,6-EET), a plant dimeric diterpenoid called bisandrographolide A (BAA), and the phorbol ester 4-alpha-phorbol-12,13-didecanoate (4α-PDD). This study focused on relevant research evidence of TRPV4 in lung disorders and its agonist and antagonist effects. TRPV4 can be a possible target of discovered molecules that exerts high therapeutic potential in the treatment of respiratory diseases by inhibiting TRPV4.

Development of insecticide-impregnated polyester/cotton blend fabric and assessment of their repellent characteristics against Cimex lectularius and dengue vectors Aedes albopictus and Aedes aegypti.

BACKGROUND: Personal protection measures using insecticide-treated fabric is one of the most effective strategies to prevent the bites of hematophagous insects. Many countries have had success treating fabrics with pyrethroids on an individual level. METHODS: In the current study, a new combination of insecticides, alpha-cypermethrin (ACP) and deltamethrin (DET), has been impregnated on fabric composed of a 50:50 blend of polyester and cotton. Residual and morphological analysis was performed along with the evaluation of physical parameters. Biological evaluations were performed to check the repellency, knockdown, and mortality of insecticide-impregnated fabric (IIF) against bed bugs (Cimex lectularius) using Petri plate assay and mosquitoes (Aedes aegypti and Aedes albopictus) using cone bioassay. RESULTS: The results showed the repellency of IIF to be 56.6% for C. lectularius and a knockdown percentage of 53.3% and 63.3% for Ae. aegypti and Ae. albopictus, respectively. A > 80% mortality was found for both species of mosquitoes up to 20 cycles of washing with no significant difference (P > 0.05). From high-performance liquid chromatography (HPLC) analysis, the reduction in the contents of ACP and DET after subsequent washes can be correlated with the overall decrease in bioefficacy. ACP and DET remaining in unit gram of fabric after 20 wash cycles were found to be 5.4 mg and 3.1 mg, respectively. By examining the fabric's surface morphology using scanning electron microscope (SEM) and utilizing energy-dispersive x-ray (EDX) analysis, it was possible to identify the presence of insecticides that were adhered to the fabric. Differential scanning calorimetry (DSC) showed distinctive endothermic peak of insecticide at 98.3 ºC, whereas no change in thermal behavior was observed from thermo-gravimetric analysis (TGA). Furthermore, the physical attributes of IIF provide conclusive evidence for its firmness. CONCLUSION: All experimental findings were consistent with the potential use of IIF as a bed bug- and mosquito-repellent fabric to be used against hematophagous infestations. This fabric can serve as a potential strategy to control vector-borne diseases like dengue, malaria, trench fever, etc.

Therapeutic potential of bioactive phytoconstituents found in fruits in the treatment of non-alcoholic fatty liver disease: A comprehensive review.

Nonalcoholic fatty liver disease (NAFLD), a chronic liver condition affects a large number of people around the world with a frequency of 25% of all the chronic liver disease worldwide. Several targets viz. anti-inflammatory, anti-apoptotic and, anti-fibrotic factors, anti-oxidant and insulin-sensitizing pathways, metabolic regulators as well as repurposing traditional medications have been studied for the pharmacologic therapy of NAFLD. Newer pharmacotherapies like caspases blockade, agonists of PPAR and farnesoid X receptor agonists are currently being investigated in treating human NAFLD. However, NAFLD has no FDA-approved pharmacological therapy, therefore there is a considerable unmet therapy need. Apart from the conventional treatment regime, the current approaches to treating NAFLD include lifestyle interventions including healthy diet with adequate nutrition and physical activity. Fruits are known to play a key role in the well-being of human health. Fruits are loaded with a repertoire of bioactive phytoconstituents like catechins, phytosterols, proanthocyanidin, genestin, daidzen, resveratrol, magiferin found in fruits like pear, apricot, strawberries, oranges, apples, bananas, grapes, kiwi, pineapple, watermelon, peach, grape seed and skin, mango, currants, raisins, dried dates, passion fruit and many more. These bioactive phytoconstituents are reported to demonstrate promising pharmacological efficacy like reduction in fatty acid deposition, increased lipid metabolism, modulation of insulin signaling pathway, gut microbiota and hepatic inflammation, inhibition of histone acetyltransferase enzymatic activity to name a few. Not only fruits, but their derivatives like oils, pulp, peel, or their preparations are also found to be equally beneficial in various liver diseases like NAFLD, NASH. Although most of the fruits contains potent bioactive phytoconstituents, however, the presence of sugar in fruits put a question mark on the ameliorative property of the fruits and there has been contrasting reports on the glycemic control post fruit consumption in type 2 diabetic patients. This review is an attempt to summarize the beneficial effects of fruit phytoconstituents on NAFLD based on epidemiological, clinical and experimental evidence, focusing especially on their mechanisms of action.

Synthesis of salicylic acid phenylethyl ester (SAPE) and its implication in immunomodulatory and anticancer roles.

Salicylic acid phenylethyl ester (SAPE) was synthesized by Zn(OTf)2-catalyzed selective esterification of salicylic acid and phenylethyl alcohol and studied for its role as an immunomodulatory and anticancer agent. Low toxicity and favorable physical, Lipinski-type, and solubility properties were elucidated by ADME-tox studies. Molecular docking of SAPE against COX-2 revealed favorable MolDockscore, rerank score, interaction energy, internal pose energy, and hydrogen bonding as compared to ibuprofen and indomethacin. An average RMSD of ~ 0.13 nm for the docked complex with stable dynamic equilibrium condition was noted during the 20 ns MD simulation. A low band gap predicting a strong binding affinity at the enzyme's active site was further predicted by DFT analysis. The ester caused a reduction in the percentage of erythrocyte hemolysis and was shown to be non-cytotoxic against human lymphocytes, CaCo-2, and HepG-2 cells by the MTT assay. Moreover, it's in vitro efficacy in inhibiting COX-2 enzyme under both LPS stimulated intestinal cells and direct sequestration assays was found to be higher than salicylic acid and indomethacin. The anticancer activity of SAPE was tested on the breast cancer cell line MCF-7, and potential efficacy was exhibited in terms of decreased cell viability. Flow cytometry analysis exhibited the arrest of the cell cycle at G1/G0 and S phases, during which induction of autophagic vesicle formation and decrease in mitochondrial membrane potential was observed owing to increased ROS production. Furthermore, at these phases, the onset of apoptosis along with DNA damage was also observed. Pre-treatment with SAPE in colitis-induced Wistar rats displayed low disease activity index and reduction in the extent of intestinal tissue disruption and lipid peroxidation. A marked increase of anti-oxidative enzymes viz., catalase, GGT, and GST, and a decrease of pro-inflammatory cytokines IL-6 and TNF-α in the intestinal tissue extracts of the treated groups was noted. The results of this study have sufficient credence to support that the synthesised ester (SAPE) be considered as an anti-oxidative and anti-inflammatory compound with therapeutic potential for the effective management of cancer.

The fabrication and assessment of mosquito repellent cream for outdoor protection.

Mosquito-borne infections like dengue, malaria, chikungunya, etc. are a nuisance and can cause profound discomfort to people. Due to the objectional side effects and toxicity associated with synthetic pyrethroids, N,N-diethyl-3-methylbenzamide (DEET), N,N-diethyl phenylacetamide (DEPA), and N,N-di ethyl benzamide (DEBA) based mosquito repellent products, we developed an essential oil (EO) based mosquito repellent cream (EO-MRC) using clove, citronella and lemongrass oil. Subsequently, a formulation characterization, bio-efficacy, and safety study of EO-MRC were carried out. Expression of Anti-OBP2A and TRPV1 proteins on mosquito head parts were studied by western blotting. In-silico screening was also conducted for the specific proteins. An FT-IR study confirmed the chemical compatibility of the EOs and excipients used in EO-MRC. The thermal behaviour of the best EOs and their mixture was characterized by thermogravimetric analysis (TGA). GC-MS examination revealed various chemical components present in EOs. Efficacy of EO-MRC was correlated with 12% N,N-diethyl benzamide (DEBA) based marketed cream (DBMC). Complete protection time (CPT) of EO-MRC was determined as 228 min. Cytotoxicity study on L-132 cell line confirmed the non-toxic nature of EO-MRC upon inhalation. Acute dermal irritation study, acute dermal dose toxicity study, and acute eye irritation study revealed the non-toxic nature of EO-MRC. Non-target toxicity study on Danio rerio confirmed EO-MRC as safer for aquatic non-target animals. A decrease in the concentration of acetylcholinesterase (AChE) was observed in transfluthrin (TNSF) exposed Wistar rats. While EO-MRC did not alter the AChE concentrations in the exposed animals. Results from western blotting confirmed that Anti-OBP2A and TRPV1 proteins were inhibited in TNSF exposed mosquitoes. Mosquitoes exposed to EO-MRC showed a similar expression pattern for Anti-OBP2A and TRPV1 as the control group. In silico study revealed eight identified compounds of the EOs play significant roles in the overall repellency property of the developed product. The study emphasizes the mosquito repellent activity of EO-MRC, which could be an effective, eco-friendly, and safer alternative to the existing synthetic repellents for personal protection against mosquitoes during field conditions.

Assessment of toxicological consequences upon acute inhalation exposure to chemically improvised nonlethal riot control combinational formulation (NCF) containing oleoresin capsicum and skatole.

Sensory irritation is an acute adverse effect leading to temporary disability posed by riot control agents in various deployable forms are utilized by defense personal in violent mob attacks but their irreversible toxic effects and risk assessment have been a matter of concern. These intimidating risks of available riot control agents have led to exploring the pulmonary toxicity profile of the oil in water emulsion formulation developed for vicious crowd controls containing an irritant oleoresin capsicum, a malodorant (skatole), and a commercial dye, followed by characterization using standard methods. Nonlethal riot control combinational formulation (NCF) has been aimed to be the best possible low-lethal alternative for riot control measures. In this study, 30 min of acute inhalation exposure of NCF was given to Wistar rats and various respiratory parameters like lung dynamics, bronchoalveolar lavage fluid (BALF) cytological assays, pro-inflammatory cytokines estimation, antioxidant activity, collagen accumulation, cytotoxicity, in vivo lung imaging, western blot, histology of lung tissue, etc. were investigated to validate its potentiality and rate of irritation reversibility as nonlethal agents. An exaggerated physiological change like sensory irritation, changes in lung functional variables, increased pro-inflammatory cytokines, etc. were noticed initially without airway obstruction as the expression of nociceptive TRPV1 protein did not alter the physiological regulation of protective proteins like Nrf2 and HO-1 and also no abnormality was found in lung tissue architecture. In conclusion, it can be stated that this formulation can be explored as a nonlethal riot control agent intending to generate discomfort but with early reversibility of sensory irritation and no recurrence of toxicity.

Exploring the frostbite healing potential of hyaluronic acid based hydrogel of Manuka honey through in-silico antithrombotic and anti-platelet studies of major phytoconstituents and in-vivo evaluation in Wistar rat model.

OBJECTIVE: Development of Frostbite healing hydrogel of Manuka honey and hyaluronic acid. SIGNIFICANCE: Frostbite is a cold-induced ischemic vascular injury non-responsive to most of the wound healing products. Thrombus-induced ischemia is the main cause of frostbite-related necrosis. Hyaluronic acid is known to possess significant antithrombotic and wound healing activity. Moreover, Manuka Honey is also rich in flavonoids and polyphenols with potential antithrombotic activity. These two agents were together utilized to develop a frostbite healing formulation. METHODS: In-silico antithrombotic efficacy of major phytoconstituents of Manuka honey was evaluated using in-silico-docking studies against Tissue plasminogen activator and Cyclooxygenase-1 protein. Further in-vivo frostbite healing evaluation was carried out in Wistar rats, by inducing frostbite with a supercooled rod. RESULTS: The results indicate that major leptosin and other major phytoconstituent of Manuka honey has significant antithrombotic property. The hydrogel formulation of HA and MH possess significant antimicrobial efficacy. The wound contraction studies and histopathological evaluation reveals that the hydrogel also has a good frostbite healing activity showing complete wound healing within an 18-day period. The findings of the western blotting studies suggest that the hydrogel acts by VEGF- NRF-2 pathway. CONCLUSION: This result implies that the prepared hydrogel can serve as an effective frostbite healing formulation.

Crosstalk between AdipoR1/AdipoR2 and Nrf2/HO-1 signal pathways activated by ß-caryophyllene suppressed the compound 48/80 induced pseudo-allergic reactions.

Mast cell activation is initiated by two signalling pathways: immunoglobulin E (IgE)-dependent and IgE-independent pathway. It is reported that the IgE-independent type or pseudo-allergy pathway gets activated by G-protein-dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 have been identified as G-protein-coupled receptors (GPCRs). Interestingly, APN replenishment is reported to activate the Nrf2/HO-1 signalling axis. However, no study has been performed interlinking the role of APN and the Nrf2/HO-1 signalling axis in pseudo-allergic reaction. In the present study, we evaluated the anti-pseudo-allergic effects of ß-caryophyllene, an FDA-approved food additive, in activating AdipoR1/AdipoR2 and Nrf2/HO-1 axis signalling pathway. Compound 48/80 (C48/80)-induced systemic and cutaneous anaphylaxis-like shock in BALB/c mice was performed to assess the efficacy of ß-caryophyllene (BCP). To assess the effect of BCP in anaphylactic hypotension, mean arterial pressure was measured in Wistar rats. Inhibitory properties of BCP in mast cell degranulation were estimated in rat peritoneal mast cells (RPMCs). ELISA was performed to estimate interleukin (IL)-6, tumour necrosis factor (TNF), IL-1ß, IgE, ovalbumin (OVA)-IgE and APN and western blotting for protein expression of Nrf2/HO-1 and AdipoR1-AdipoR2. BCP dose-dependently inhibited systemic and cutaneous anaphylaxis-like shock induced by C48/80. BCP dose-dependently inhibited the mast cell degranulation followed by inhibition of histamine release. Also BCP dose-dependently activated the Nrf2/HO-1 and AdipoR1-AdipoR2 signalling axis pathway. Moreover, BCP reversed the drop in blood pressure when the haemodynamic parameters were accessed. Our findings suggest that BCP is a potent AdipoR1/AdipoR2-Nrf2/HO-1 axis pathway agonist that may suppress the IgE-independent pathway towards allergic response to secretagogues.

ß-caryophyllene ameliorated obesity-associated airway hyperresponsiveness through some non-conventional targets.

BACKGROUND: Obesity worsens airway hyperresponsiveness (AHR) in asthmatic subjects by up-regulating macrophage polarization that leads to excessive secretion of pro-inflammatory adipokines from white adipose tissue followed by generation of oxidative stress in the respiratory system. Treatment through conventional signaling pathways proved to be inadequate in obese asthmatics, so a therapeutical approach through a non-conventional pathway may prove to be effective. PURPOSE: This study aimed to investigate the efficacy of a FDA-approved food additive, ß-caryophyllene (BCP) in obesity-associated AHR. METHOD: A repertoire of protein expression, cytokine and adiponectin estimation, oxidative stress assays, histopathology, and fluorescence immune-histochemistry were performed to assess the efficacy of BCP in C57BL/6 mice model of obesity-associated AHR. Additionally, human adipocyte was utilized to study the effect of BCP on macrophage polarization in Boyden chamber cell culture inserts. RESULTS: Obesity-associated AHR is ameliorated by administration of BCP by inhibition of the macrophage polarization by activation of AMPKα, Nrf2/HO-1 and AdipoR1 and AdipoR2 signaling pathway, up-regulation of adiponectin, GLP-1, IFN-γ, SOD, catalase and down-regulation of NF-κB, leptin, IL-4, TNF, and IL-1ß. Browning of eWAT by induction of thermogenesis and activation of melanocortin pathway also contributed to the amelioration of obesity-associated AHR. We conclude that BCP ameliorated the obesity-associated AHR via inhibition of macrophage polarization, activation of AMPKα, Nrf2/HO-1, and up-regulation of AdipoR1 and AdipoR2 expression and down-regulation of NFκB expression in lung of animal. CONCLUSION: Being an FDA-approved food additive, BCP may prove to be a safe and potential agent against obesity-associated AHR.

bFGF and collagen matrix hydrogel attenuates burn wound inflammation through activation of ERK and TRK pathway.

Burn injuries are most challenging to manage since it causes loss of the integrity of large portions of the skin leading to major disability or even death. Over the years, hydrogels are considered as a significant delivery system for wound treatment because of several advantages over other conventional formulations. We hypothesized that the bFGF-collagen-AgSD incorporated hydrogel formulation can accelerate the rate of burn healing in animal model and would promote fibroblast cell proliferation. Neovascularization and re-epithelialization is a hall mark of burn wound healing. In the present study, histopathological investigation and scanning electron microscopy of skin tissue of Wistar rats showed almost complete epithelialisation after 16 days in the treatment group. The developed hydrogel showed significantly accelerated wound closure compared with a standard and control group. The faster wound closure resulted from increased re-epithelialization and granulation tissue formation because of the presence of collagen and growth factor. Expressions of proteins such as TrkA, p- TrkA, ERK1/2, p-ERK1/2, NF-kß, and p-NF-kß involved in nerve growth factor (NGF) signalling pathway were analysed by western blot. All the findings obtained from this study indicated that the hydrogel can be considered as a promising delivery system against second degree burn by faster healing.