Fabrication of poly (lactic-co-glycolic acid)/gelatin electro spun nanofiber patch containing CaCO3/SiO2 nanocomposite and quercetin for accelerated diabetic wound healing.

An open wound or sore on the bottom of the foot caused by diabetes is known as a diabetic foot ulcer. Preventive measures are essential, including consistent foot care and glycemic management. The dangers associated with diabetic foot ulcers can be reduced via early identification and timely treatment. The risk of foot ulcers and limb amputation increases with age and duration of diabetes. Quercetin contains anti-inflammatory and antioxidant properties. Furthermore, the calcium carbonate/silica (CaCO3/SiO2) nanocomposite has a good anti-inflammatory property due to the presence of calcium, which will aid in wound healing. As a result, combining quercetin (plant based anti-inflammatory drug) and CaCO3/SiO2 nanocomposite will boost the wound healing rate. We have synthesized CaCO3/SiO2 nanocomposite in sol-gel method and characterized using XRD, FTIR and TEM. Cell line tests and the MTT assay revealed that the PLGA/gelatin/CaCO3/SiO2/quercetin patch enhanced the proliferation of cells. Its anti-bacterial efficacy against four major bacterial strains often found in wound locations, as well as its water retention, make it an ideal material for diabetic wound healing. In-vivo trials confirms the enhanced diabetic wound healing potential of the patch.

Insights on the Dynamics and Toxicity of Nanoparticles in Environmental Matrices.

The manufacturing rate of nanoparticles (10-100 nm) is steadily increasing due to their extensive applications in the fabrication of nanoproducts related to pharmaceuticals, cosmetics, medical devices, paints and pigments, energy storage etc. An increase in research related to nanotechnology is also a cause for the production and disposal of nanomaterials at the lab scale. As a result, contamination of environmental matrices with nanoparticles becomes inevitable, and the understanding of the risk of nanoecotoxicology is getting larger attention. In this context, focusing on the environmental hazards is essential. Hence, this manuscript aims to review the toxic effects of nanoparticles on soil, water, aquatic, and terrestrial organisms. The effects of toxicity on vertebrates, invertebrates, and plants and the source of exposure, environmental and biological dynamics, and the adverse effects of some nanoparticles are discussed.

A novel, highly sensitive electrochemical 1,4-dioxane sensor based on reduced graphene oxide-curcumin nanocomposite.

1,4-Dioxane is a carcinogenic, non-biodegradable, organic water pollutant which is used as a solvent in various industries. It is also formed as an undesired by-product in the cosmetic and pharmaceutical industry. Given its carcinogenicity and ability to pollute, it is desirable to develop a sensitive and selective sensor to detect it in drinking water and other water bodies. Current works on this sensor are very few and involve complex metal oxide composite systems. A sensitive electrochemical sensor for 1,4-dioxane was developed by modifying a glassy carbon electrode (GCE) with a reduced graphene oxide-curcumin (rGO-CM) nanocomposite synthesized by a simple solution approach. The prepared rGO-CM was characterized by X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy, Raman spectroscopy, UV-Vis spectroscopy, and Scanning Electron Microscopy (SEM). The rGO-CM/GCE sensor was employed for the detection of 1,4-dioxane in the range of 0.1-100 µM. Although, the detection range is narrower compared to reported literature, the sensitivity obtained for the proposed sensor is far superior. Moreover, the limit of detection (0.13 µM) is lower than the dioxane detection target defined by the World Health Organization (0.56 µM). The proposed rGO-CM/GCE also showed excellent stability and good recovery values in real sample (tap water and drinking water) analysis.

Curcumin Is an Iconic Ligand for Detecting Environmental Pollutants.

The rapid increase in industrial revolution and the consequent environmental contamination demands continuous monitoring and sensitive detection of the pollutants. Nanomaterial-based sensing system has proved to be proficient in sensing environmental pollutants. The development of novel ligands for enhancing the sensing efficiency of nanomaterials has always been a challenge. However, the amendment of nanostructure with molecular ligand increases the sensitivity, selectivity, and analytical performance of the resulting novel sensing platform. Organic ligands are capable of increasing the adsorption efficacy, optical properties, and electrochemical properties of nanomaterials by reducing or splitting of band gap. Curcumin (diferuloylmethane) is a natural organic ligand that exhibits inherent fluorescence and electrocatalytic property. Due to keto-enol tautomerism, it is capable of giving sensitive signals such as fluorescence, luminescence, ultraviolet absorption shifts, and electrochemical data. Curcumin probes were also reported to give enhanced meterological performances, such as low detection limit, repeatability, reproducibility, high selectivity, and high storage stability when used with nanosystem. Therefore, research on curcumin-modified nanomaterials in the detection of environmental pollution needs a special focus for prototype and product development to enable practical use. Hence, this article reviews the role of curcumin as a natural fluorophore in optical and electrochemical sensing of environmentally significant pollutants. This review clearly shows that curcumin is an ideal candidate for developing and validating nanomaterials-based sensors for the detection of environmental pollutants such as arsenic, lead, mercury, boron, cyanide, fluoride, nitrophenol, trinitrotoluene, and picric acid and toxic gases such as ammonia and hydrogen chloride. This review will afford references for future studies and enable researchers to translate the lab concepts into industrial products.

Characterization of NCC-RbC-51, an RB cell line isolated from a metastatic site.

Retinoblastoma (RB) is a childhood eye tumor, caused by the RB1 gene mutation. Since RB is a rapidly proliferating tumor, the patient presents with a Group-D/E tumor at the time of diagnosis. Enucleation is preferred in most unilateral cases to prevent metastasis. Various cell lines have been established to study the tumor's growth pattern and target the cancer cells. The commonly used cell lines are WERI-Rb-1 and Y79, both isolated from the primary tumor of RB. Cell lines established from the metastatic site of RB have not been characterized before. In this study, we have characterized NCC-RbC-51, derived from RB tumor to cervical lymph node site and investigated its potential to represent a highly aggressive and metastatic tumor. We compared the proliferative and invasive properties of NCC-RbC-51 with a cell line isolated from the primary site, WERI-Rb-1. NCC-RbC-51 had higher rates of proliferation and apoptosis and had better invasive ability. Copy number variation analysis and the pathways predicted from these show that the pathways altered in NCC-RbC-51 could contribute to its metastatic nature. In all, the results suggest that NCC-RbC-51, a cell line isolated from metastatic site, could be a potential model to study aggressive/invasive RB.

Non-cytotoxic effect of green synthesized silver nanoparticles and its antibacterial activity.

Silver nanoparticles (AgNPs) were green synthesized using ethanolic extract of fenugreek leaves and characterized using UV-Vis spectroscopy, Fourier transform infra-red spectroscopy (FTIR), X-ray diffraction (XRD), high resolution transmission electron microscopy HRTEM and energy dispersive X-ray analysis (EDX) techniques. The HRTEM results revealed the formation of highly stable, mono dispersed, spherical shaped AgNPs with the size ranging from 20 to 30nm. The presence of flavonoids and their interaction with the AgNPs were confirmed using FTIR. Antibacterial activities of the AgNPs were studied against pathogenic gram-positive Staphylococcus aureus (S. aureus) and gram negative Escherichia coli (E. coli) bacteria. The synthesized AgNPs displayed the enhancement of antibacterial activity against E. coli. The morphological changes in the bacterial cell membrane was observed using SEM analysis. Leakage of protein from the bacterial cells increased at every time intervals (2 and 4h). MTT assay was carried out for the AgNPs against human skin cell line (HaCaT). Interestingly, cytotoxicity of the synthesized AgNPs was less toxic to HaCaT cells as compared to bacteria cells, which suggests that the synthesized AgNPs by this method is eco-friendly in nature.

Green Synthesis of Silver Nanorods and Optimization of Its Therapeutic Cum Toxic Dose.

Germinated Fenugreek seeds are relatively rich in flavonoids and polyphenols than dry seeds. Therefore, germinated fenugreek seeds possess better pharmacological activities. We have used an aqueous extract of germinated fenugreek seeds to reduce silver nitrate into nanoscale silver rods. The silver nanorods showed Surface Plasmon peak at 450 nm as revealed from UV visible spectrum. Field Emission Scanning Electron Microscopy images revealed the monodispersity and rod morphology. X ray diffraction spectrum revealed the FCC crystal structure of nanorods. Fourier transform infrared spectroscopy peaks revealed the interaction between the phytochemicals of germinated fenugreek seeds and the silver nanorods. Characterization studies reveal the validation of the proposed green synthesis protocol to produce monodispersed silver nanorods with phytochemical capping. The phytosynthesized silver nanorods exhibited anticancer activity in skin cancer cell line, which may be due to its nanoscale dimension and the surface functionalization. For the first time, we have optimized the therapeutic cum toxic dose of phytostabilized silver nanorods using skin cancer cell model.

Determination of LC50 and sub-chronic neurotoxicity of diesel exhaust nanoparticles.

Air pollution is a major problem faced globally and is seen associated with central nervous system (CNS) disorders like neuropathology and neuro-inflammation. Here, we investigated the CNS disorders as a result of sub-chronic exposure (90 days) to diesel exhaust nanoparticles (DENPs) and explored the minimal levels of DENPs needed to exhibit the early mediators of neuro-inflammation and neuropathology. Male and female wistar rats (6 rats per group) were exposed to DENPs (1/5th, 1/10th and 1/15th LC50) by inhalation for 4h per day, 5 days per week over 90 days and neurotoxicity end-points were analyzed. DENP exposure caused elevation in levels of pro-inflammatory cytokines, amyloid beta 42 (Aß 42), reactive oxygen species (ROS), hydrogen peroxide (H2O2), nitrate (NO3(-)), nitrite (NO2(-)) and apurinic/apyrimidinic sites (AP) at varying degrees at different sections of rat brain. Hence, exposure to DENPs resulted in dose-dependent toxicity and was closely correlated to increased inflammation, DNA damage and oxidative stress.

Facile Synthesis of Curcumin Nanocrystals and Validation of Its Antioxidant Activity Against Circulatory Toxicity in Wistar Rats.

Our investigation was carried out in two phases. First we synthesized curcumin nanocrystals using a simple precipitation method and characterized their absorbance, crystallinity, size, and morphology by UV-visible spectroscopy, X-ray diffraction (XRD) spectroscopy, High Resolution Transmission Electron Microscopy (HRTEM) and Particle size Analyzer (PSA), in comparison with bulk curcumin. Characterization studies revealed that the protocol we standardized resulted in Curcumin nanocrystals with 10-200 nm size which was fairly soluble in water in contrast to bulk curcumin. Due to its crystallinity, nanocurcumin that we synthesized was also referred as Curcumin Nanocrystals. In Phase 2, we have assessed the comparative antioxidant efficacy of Curcumin nanocrystals and bulk Curcumin in the circulation of 1,2-dimethyl hydrazine-treated rats by investigating lipid peroxidation, antioxidant enzymes (superoxide dismutase, catalase), GSH and GSH-dependent detoxification enzymes (glutathione peroxidase, gIutathione-S-transferase). Curcumin nanocrystals exerted its antioxidant effect by decreasing lipid peroxidation, and by enhancing the activities of antioxidant and detoxification enzymes studied. Curcumin nanocrystals exhibited its antioxidant action at 40 mg dose whereas the bulk curcumin exerted its effect at 80 mg dose. This may be due to enhanced solubility, dispersibility, and crystallinity of the nanocrystals, which might have enhanced its bioavailability when compared to poorly soluble bulk curcumin.

Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis.

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer

Chemoprevention of colon cancer by a synthetic curcumin analog involves amelioration of oxidative stress.

The modulating effects of a bisdemethoxycurcumin analog (BDMC-A) on 1,2-dimethylhydrazine (DMH)-induced oxidative stress during colon carcinogenesis was investigated in male Wistar rats. The effects were compared with those of curcumin, a known anticarcinogen. All the animals given a weekly subcutaneous injection of DMH (20 mg/kg body wt.) for 15 weeks developed colon tumors. The colon and intestine administered DMH showed a decrease in lipid peroxidation with a concomitant increase in the activities of GSH-dependent enzymes (glutathione peroxidase, glutathione S-transferase) when compared to untreated control rats. In groups of animals given DMH and BDMC-A no tumors were observed, and the lipid peroxidation as well as the GSH-dependent enzymes showed a pattern similar to that of untreated control rats. We speculate that BDMC-A modulates DMH-induced oxidative stress and offers chemoprevention against colon carcinogenesis, and the modulatory effect is comparable with that of curcumin. Thus, lipid peroxidation and antioxidant status together could be used as markers of colon cancer chemoprevention by BDMC-A.

Fenugreek affects the activity of beta-glucuronidase and mucinase in the colon.

The effect of fenugreek seeds on the activities of beta-glucuronidase and mucinase during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats was studied. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight, for 15 weeks. Fenugreek seed powder was weighed depending upon the weight of individual rats and incorporated in the powdered pellet diet at a dose of 2 g/kg body weight. After an experimental period of 30 weeks the activity of beta-glucuronidase significantly increased in the colon, intestine, liver and colon contents in DMH administered rats when compared to an untreated control group. Increase in beta-glucuronidase may increase the hydrolysis of carcinogen-glucuronide conjugate, liberating carcinogen and/or co-carcinogen within the colonic lumen. Inclusion of fenugreek seed powder in the diet significantly decreased the activity of beta-glucuronidase in all the tissues studied. This may prevent the free carcinogens from acting on colonocytes. Mucinase helps in hydrolysing the protective mucin. Mucinase activity was increased in the colon content and fecal content of animals given DMH when compared to control, while the activity was significantly reduced in animals given DMH + fenugreek when compared to animals given DMH only. Our study shows that supplementation of fenugreek seeds in the diet inhibits colon carcinogenesis, by modulating the activities of beta-glucuronidase and mucinase. The beneficial effect may be attributed to the presence of fibre, flavonoids and/or saponins.

Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model.

1,2-Dimethylhydrazine (DMH) is a toxic environmental pollutant which was reported also to be a colon-specific carcinogen. This study was performed to study the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxycurcumin analog (BDMC-A) on DMH-induced colon carcinogenesis in male Wistar rats and effects were compared with that of the reference drug, curcumin. Rats were given a weekly subcutaneous injection of DMH (20mg/kg body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization) tumor incidence was 100% in DMH-treated rats. Tumor was identified histologically as adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in DMH-treated rats. However, there was no colonic tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total bile acids and cholesterol in 24h fecal samples were significantly lower in DMH administered rats when compared to control rats, while, the excretion of bile acids and cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In DMH-induced tumor bearing rats the levels of colonic and intestinal cholesterol was significantly increased whereas, the levels of phospholipid was decreased with a concomitant increase in the activities of phospholipase A (PLA) and phospholipase C (PLC), compared to untreated control rats. Intragastric administration of BDMC-A and curcumin to DMH administered rats significantly lowered the cholesterol content and raised the phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of BDMC-A during DMH-induced colon carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii). bile acids, (iii). cholesterol, and (iv). phospholipid metabolism in the target organ. Absence of histological changes in the colon of rats treated with BDMC-A, shows that long term administration of BDMC-A is nontoxic to experimental animals. Our study suggest that BDMC-A may emerge as a potent anticarcinogenic agent against colon cancer. As both BDMC-A and curcumin are equipotent in inhibiting the DMH-induced colon tumor incidence and normalizing histological changes, it could be concluded that the terminal phenolic group and the conjugated double bonds in the central seven carbon change may be responsible for the beneficial effects.

Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis.

The protective effect of a curcumin analog [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] was investigated on hepatic lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. The effects were compared with that of curcumin, a known antioxidant and anticarcinogen. Colon cancer was induced by sub-cutaneous injection of DMH at a dosage of 20mg/kg body weight (15 doses, at 1-week intervals). DMH administered rats developed gross tumours in the colon. Enhanced lipid peroxidation in the liver of colon tumour bearing rats was accompanied by a significant decrease in the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Intragastric administration of curcumin (80mg/kg body weight) and curcumin analog (80mg/kg body weight) to DMH-injected rats significantly reduced the number and size of tumour in the colon, lowered lipid peroxidation and enhanced the activities of GPx, GST, SOD and CAT in the liver. We speculate that the curcumin analog used in the present study exerts chemoprevention against cancer development at extrahepatic sites by modulating hepatic biotransformation enzymes and antioxidant status. The effect is comparable with that of curcumin. This shows that the hydroxyl group in the aromatic ring is responsible for the protective effect rather than the methoxy group.

Enhancement of circulatory antioxidants by fenugreek during 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

We have investigated the modulatory effect of fenugreek seeds (a spice) on circulatory lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Enhanced LPO in the circulation of tumor bearing animals was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase. Inclusion of fenugreek in the diet significantly decreased LPO with simultaneous enhancement of circulating antioxidants. We report that fenugreek exert its chemopreventive effect by decreasing circulatory LPO and enhancing antioxidant levels.

Lipid peroxidation, osmotic fragility and antioxidant status in children with acute post-streptococcal glomerulonephritis.

Plasma and erythrocyte samples from acute post-streptococcal glomerulonephritis (APSGN) children and control children were enrolled in this study. Lipid peroxidation (LPO), measured in terms of thiobarbituric acid-reactive substances (TBARS) was found to be significantly increased in plasma and RBCs of APSGN children (P<0.05) than in control children. Osmotic fragility of erythrocytes was examined. RBCs of APSGN patients were found to be osmotically more sensitive towards hypotonic saline (50% hemolysis at 7 g/l saline) when compared to control RBCs (50% hemolysis at 4 g/l saline). The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were significantly lowered (P<0.05) in APSGN RBCs when compared to control RBCs. Plasma ascorbic acid, reduced glutathione (GSH), RBC ascorbic acid, GSH and RBC total sulphydryl content (TSH) were significantly depleted in APSGN children relative to controls. The susceptibility of RBCs of APSGN children to lipid peroxidation was confirmed in this study.