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.

Modulation of terpenoid indole alkaloid pathway via elicitation with phytosynthesized silver nanoparticles for the enhancement of ajmalicine, a pharmaceutically important alkaloid.

MAIN CONCLUSION: The use of silver nanoparticles as elicitors in cell cultures of Rauwolfia serpentina resulted in increased levels of ajmalicine, upregulated structural and regulatory genes, elevated MDA content, and reduced activity of antioxidant enzymes. These findings hold potential for developing a cost-effective method for commercial ajmalicine production. Plants possess an intrinsic ability to detect various stress signals, prompting the activation of defense mechanisms through the reprogramming of metabolites to counter adverse conditions. The current study aims to propose an optimized bioprocess for enhancing the content of ajmalicine in Rauwolfia serpentina callus through elicitation with phytosynthesized silver nanoparticles. Initially, callus lines exhibiting elevated ajmalicine content were established. Following this, a protocol for the phytosynthesis of silver nanoparticles using seed extract from Rauwolfia serpentina was successfully standardized. The physicochemical attributes of the silver nanoparticles were identified, including their spherical shape, size ranging from 6.7 to 28.8 nm in diameter, and the presence of reducing-capping groups such as amino, carbonyl, and amide. Further, the findings indicated that the presence of 2.5 mg L-1 phytosynthesized silver nanoparticles in the culture medium increased the ajmalicine content. Concurrently, structural genes (TDC, SLS, STR, SGD, G10H) and regulatory gene (ORCA3) associated with the ajmalicine biosynthetic pathway were observed to be upregulated. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were observed. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were also observed. Our results strongly recommend the augmentation of ajmalicine content in the callus culture of R. serpentina through supplementation with silver nanoparticles, a potential avenue for developing a cost-effective process for the commercial production of ajmalicine.

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.

Larvicidal property and active compound profiling of Annona squamosa leaf extracts against two species of diptera, Aedes aegypti and Anopheles stephensi.

Background & objectives: Vector control measures are important in lowering the spread of infections spread by mosquito. Synthetic pesticides used to suppress vector populations during the larval stage have had adverse impacts on people and the environment. The early III instar larvae of Aedes aegypti and Anopheles stephensi were the targets of the current experiment, which assessed the larvicidal ability of petroleum ether, chloroform, methanol, and aqueous extracts of Annona squamosa leaves. Methods: Using the standard World Health Organization (WHO) larval bioassay test, leaf extracts were evaluated for their activity against Ae. aegypti and An. stephensi to determine lethal doses. Phytochemical analysis and gas chromatography-mass spectrometry (GC-MS) were carried out to identify larvicidal components in the extract. Further analysis using a scanning electron microscope (SEM) was done to check the extracts toxicity for both mosquito larvae. Results: The larvicidal active components were identified by GC-MS as tetradecanoic acid, cis-vaccenic acid, and 2,4-di-tert-butylphenol etc. Methanol leaf extracts of A. squamosa (ASME) exhibited strong larvicidal activity against the early 3rd instar larvae of Ae. aegypti and An. stephensi with Lethal concentration (LC50) values of 51.450 ppm and 107.121 ppm. Cell damages to the larva post exposure to ASME were examined. Interpretation & conclusion: This finding showed that the ASME has better larvicidal activity and its components that may be used to kill larvae as larvicides. The extracts toxicity towards damage of midgut of larva further suggests that this plant methanol leaf extracts could be effective in larval growth control approaches.

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.

Frostbite: Current status and advancements in therapeutics.

Frostbite is a severe ischemic injury which occurs due to the tissue vascular damage after sub-zero temperature tissue exposure. Deep frostbite can result in necrosis and may need amputation of affected tissue. Though a serious injury, it is not very well understood, and further scientific exploration is needed. This work explores the current understanding of the pathophysiology of frostbite. We reviewed the current status of the diagnostics, the drugs, the therapies and the surgical practices for prevention and management of frostbite. Advances in nanotechnology and drug delivery had improved the therapeutic outcomes significantly. This review also explored the latest advancements and researches done for development of newer therapeutics and diagnostics for frostbite care.

Design, development and assessment of an essential oil based slow release vaporizer against mosquitoes.

Mosquitoes (Diptera; Culicidae) are a biting nuisance and are of economic and health importance, especially for people living in tropical countries like India. Given the environmental concerns and health hazards of synthetic insecticides, development of natural products for the control of mosquito and mosquito-borne diseases are needed. In view of this, an essential oil based novel liquid vaporizer formulation with citronella and eucalyptus oils has been developed using a computer aided Artificial Neural Network and Particle Swarm Optimization (ANN-PSO) algorithm approach, aiming to predict the best optimized formulation (OF). Following the development, OF was characterized by Fourier Transform-Infra Red (FT-IR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). The efficacy of the OF was assessed against two major mosquito vectors viz. Anopheles stephensi and Aedes albopictus using a Peet-Grady chamber. Finally, toxicological impacts of the OF following its inhalation were investigated as per the Organization for Economic Co-operation and Development (OECD) guidelines. The results revealed all the ideal characteristics of the OF which were found to provide a slow release of up to 450 h at room temperature. Most importantly, the OF, exhibited 50% mosquito knock down (KT50) within 11.49±1.34 and 14.15±2.15 min against An. stephensi and Ae. albopictus respectively. Toxicity assessment showed a non toxic nature of the OF following inhalation. Thus the present development would be beneficial for controlling both An. stephensi and Ae. albopictus without any associated health hazards.

Amelioration from the ocular irritant Capsaicin: development and assessment of a Capsazepine in situ gel system for ocular delivery.

BACKGROUND: Defense personnel utilize capsaicin-based ocular sprays as non-lethal agents for law implementation during instances of mob violence. This study involves the capsaicin antagonist Capsazepine and the investigation of whether Capsazepine's antagonistic approach can be favorably utilized for defense utilization to block capsaicin-initiated pain and inflammation via the ocular pathway. RESEARCH DESIGN AND METHODS: Ocular capsazepine in situ gels were prepared with polymers Pluronic F-127 and Chitosan; optimized formulation was quantified in ocular tissues chromatographically and by in vivo live ocular imaging; anti-inflammatory efficacy was determined by eye irritation testing, corneal and retinal imaging, ocular prostaglandin estimation, and by viability and proliferation testing using human ocular cell lines, etc. RESULTS: A physicochemically stable Capsazepine in situ gel was formulated which showed little ocular irritation, considerable transcorneal permeation; was precisely quantified in ocular tissues by gas chromatography and in vivo live ocular imaging; showed anti-inflammatory properties against capsaicin by eye imaging experiments, prostaglandin declination and showed acceptable cytocompatibility when studied using human ocular cell lines. CONCLUSIONS: The fabricated in situ Capsazepine gel system might be promising for ocular delivery as it appears a pharmacologically potent and safe development, suitable for utilization in the ocular clinical therapy, provided there is additional research to substantiate it.

Exploration of cytotoxic and genotoxic endpoints following sub-chronic oral exposure to titanium dioxide nanoparticles.

Health hazards of titanium dioxide nanoparticles (TiO2-NPs) have raised severe concerns because of the paucity of information regarding the toxic effects among the population. In the present research, the in vitro and in vivo cytotoxic potential of TiO2-NPs were evaluated using flow cytometric techniques. Further, in vitro and in vivo genotoxic endpoints were estimated by means of comet, micronucleus (MN), and chromosomal aberration (CA) assays. In vitro analysis was performed at the concentration range of 10-100 µg/mL using murine RAW 264.7 cells. In vivo experiments were conducted on Albino mice (M/F) by exposing them to 200 and 500 mg/kg TiO2-NPs for 90 days. Decreased percentage of cell viability with higher doses of TiO2-NPs was evident in both in vitro and in vivo flow cytometric analysis. Further, an impaired cell cycle (G0/G1, S, and G2/M) was reflected in the present investigation following the exposure to TiO2-NPs. Increased comet scores such as tail length, % DNA in tail, tail moment, and olive moment were also observed with the higher doses of TiO2-NPs in vitro and in vivo comet assays. Finally, the in vivo MN and CA assays revealed the formation of MN and chromosomal breakage following the exposure to TiO2-NPs.

Determination of LCt50 of aerosolized paraquat and its pulmonary toxic implications in non-anesthetized rats.

Paraquat (PQ), a highly popular agricultural herbicide, is a serious occupational hazard with lethality reported at doses as low as 35 mg/kg body weight with intoxication occurring via inhalation or dermal route. The main objective of this study was to determine the median lethal concentration (LCt50) of paraquat through whole body exposure in adult male Wistar rats. Aerosolized PQ dissolved in water was delivered in a dose-dependent manner, to fully conscious rats confined in whole body plethysmograph (WBP), in a nebulized form with concentrations ranging from 40-200 mg/kg of air over a 4 h exposure period. Animals were observed up to 24-48 h post-exposure to observe any lethality. LCt50 estimates (±95% confidence interval) were obtained from the sequential stage-wise experiments using probit analysis. Rat lungs were examined radiologically and histopathologically. Gas chromatography-mass spectrometry (GC-MS) analysis determined the correlation of PQ accumulation in the lungs with the actual exposed dose of PQ. The actual LCt50 was found to be 218 g·min/m3 whereas 57.9 ± 2.90 µg/g of PQ accumulated in the lungs of each lifeless animal. All animals exhibited severe respiratory changes and pulmonary abnormalities. This study demonstrated that when compared with the actually exposed dose, the amount of PQ that accumulated in the lungs was very low, but enough to cause death in 50% of animal population and cause pulmonary abnormalities in each of the experimental animal. The PQ exposure carried out in WBP also facilitated the dermal absorption of aerosolized PQ, which replicated the real-life situation in workers operating with PQ.

Amelioration of UV radiation-induced photoaging by a combinational sunscreen formulation via aversion of oxidative collagen degradation and promotion of TGF-ß-Smad-mediated collagen production.

The presence of 40-50% more UV radiation in high altitude areas renders the plethora of sunscreen products available in the market virtually ineffective. In this light of event, four US FDA approved UV filters were combined with melatonin and pumpkin seed oil to produce a broad spectrum sunscreen cream, which is envisaged to provide optimum sunprotection along with enhanced antioxidant activity. The objective of this study is to evaluate the protective effect of the sunscreen cream against UV radiation-induced skin photoaging in adult Wistar albino rats and identify its possible underlying mechanism. Wistar rats were exposed to broad spectrum UV radiation for 28 days. The test group received the sunscreen formulation dermally every day prior to UV radiation. The effects of the formulation against UV induced symptoms; viz. skin thickness and edema, in vivo antioxidant activities, inflammatory cytokines, collagen content, histopathological examination and expression of specific genes established the protective activity of the formulation. The test formulation was able to mitigate the harmful effects of UV radiation by increasing in vivo SOD, GSH-Px, CAT and collagen levels; decreasing skin edema, skin thickness and cytokines like IL-6, IL-1ß, TNF-α and TGF-ß1. UV radiation induced changes in histological architecture and arrangement of collagen and elastin fibers were also prevented by the test formulation. Finally, the formulation was able to regulate the expression of COL3A1, COX-2, bFGF, VEGF-C, Smad2, Smad4, Smad7 genes which induced significant photoprotective activity. The sunscreen formulation ameliorated UV induced photoaging by preventing oxidative collagen degradation and augmentation of TGF-ß-Smad-mediated collagen production.

Graphene Family of Nanomaterials: Reviewing Advanced Applications in Drug delivery and Medicine.

Graphene in nano form has proven to be one of the most remarkable materials. It has a single atom thick molecular structure and it possesses exceptional physical strength, electrical and electronic properties. Applications of the Graphene Family of Nanomaterials (GFNs) in different fields of therapy have emerged, including for targeted drug delivery in cancer, gene delivery, antimicrobial therapy, tissue engineering and more recently in more diseases including HIV. This review seeks to analyze current advances of potential applications of graphene and its family of nano-materials for drug delivery and other major biomedical purposes. Moreover, safety and toxicity are the major roadblocks preventing the use of GFNs in therapeutics. This review intends to analyze the safety and biocompatibility of GFNs along with the discussion on the latest techniques developed for toxicity reduction and biocompatibility enhancement of GFNs. This review seeks to evaluate how GFNs in future will serve as biocompatible and useful biomaterials in therapeutics.

Safety evaluation of an oat grain alkaloid gramine by genotoxicity assays.

Gramine is a natural indole alkaloid that has been isolated from different raw plants occurring mainly in Avena sativa, etc. The study was aimed to investigate the possible in vitro antioxidant, in vitro mutagenic, in vitro antimutagenic, and in vivo genotoxic activity of gramine using ferric reducing ability of plasma (FRAP) assay, Metal chelating, Ames bacterial reverse mutation test, and the mouse bone marrow micronucleus assay as well as chromosomal aberration. Four concentrations of gramine viz. 250, 500, 1000, and 2000 µg/mL were evaluated for its antioxidant activity in FRAP Assay and Metal Chelating Test. Four concentrations of gramine (1250 µg/plate, 2500 µg/plate, 5000 µg/plate, and 10 000 µg/plate) were employed in Salmonella typhimurium strains to study the mutagenicity in the presence and absence of standard mutagens, 2-aminofluorene (2-AF), sodium azide (SA), and 2-nitrofluorene (2-NF). Three doses, i.e. 0.1, 0.2, and 0.3 × the LD50 of gramine (i.e. 50 mg/kg, 100 mg/kg, and 150 mg/kg) were administered orally to either sex of Swiss albino mice for 48 h to study the genotoxic activity in micronucleus assay as well as chromosomal aberration. Gramine showed potent antioxidant activity in both the assay. Gramine at the given dose lacks mutagenicity as well as found to possess antimutagenic efficacy. Interestingly, S9 enzymes increase the antimutagenic activity in a dose-dependent manner. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs), as well as no significant difference in the percentage of chromosomal aberrations was observed between the gramine groups and the negative groups but percentage of polychromatic erythrocytes (PCEs) is found to be higher in all the gramine groups. These results indicate significant antioxidant, non-mutagenic as well as non-genotoxic activity of gramine in vitro and in vivo in the given doses.