Accumulation of heavy metals from single and combined olive mill wastewater and pomace in soil and bioaccumulation in tissues of two earthworm species: Endogeic (Aporrectodea trapezoides) and Epigeic (Eisenia fetida).

Soil and earthworms are threatened by anthropogenic contamination resulting from olive mill waste dumping on the soil due to their pollutant properties. While several studies have explored the effects of olive mill waste on soil properties and the accumulation of heavy metals in soil, there is currently a gap in the literature regarding the potential bioaccumulation of heavy metals from olive mill waste in earthworms. In this study, soil with earthworms from two ecological categories (endogeic: Aporrectodea trapezoides and epigeic: Eisenia fetida) was treated with increasing doses of olive mill wastewater (OMWW) and olive mill pomace (OMP), applied individually or combined, in an indoor experiment in plastic containers, under laboratory conditions. The results revealed the presence of significant concentrations of heavy metals in the two types of wastes ranging as follows: Fe˃ Zn˃ Cu˃ Cd˃ Cr for OMWW, and Fe˃ Zn˃ Cu˃ Cr for OMP (with Cd below the detection limit). The study demonstrated distinct effects of OMWW and OMP, both individually and in combination, on soil heavy metal content, ranging as follows: soil OMWW > soil Combination > soil OMP for Cd; soil Combination > soil OMWW > soil OMP for Cr and Fe; and soil Combination > soil OMP > soil OMWW for Cu and Zn. Additionally, our investigation showed that both earthworm species exhibited significant uptake of these metals into their tissues, particularly the endogeic species. Interestingly, the most significant difference between species was in the accumulation of Cu, with the epigeic species accumulating significantly lower amounts.

Chitosan/PLA-loaded Magnesium oxide nanocomposite to attenuate oxidative stress, neuroinflammation and neurotoxicity in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-beta (Aß) aggregation, neuroinflammation, oxidative stress, and dysfunction in the mitochondria and cholinergic system. In this study, the synthesis of chitosan-polylactic acid-loaded magnesium oxide nanocomposite (CH/PLA/MgONCs) was examined using the green precipitation method. The synthesized CH/PLA/MgONCs were confirmed by using the UV-Vis spectrum, FT-IR, SEM-EDAX, and physical properties. The experiments were carried out using male Wistar rats by injecting streptozotocin (STZ) bilaterally into the brain's ventricles through the intracerebroventricular (ICV) route at a dose of 3 mg/kg. We also evaluated the effects of CH/PLA/MgONCs at doses of 10 mg/kg. To assess the cognitive dysfunction induced by ICV-STZ, we performed behavioral, biochemical, and histopathological analyses. In our study results, UV-Vis spectrum analysis of CH/PLA/MgONCs showed 285 nm, FT-IR analyses confirmed that the various functional groups were present, and SEM-EDAX analysis confirmed that a cauliflower-like spherical shape, Mg and O were present. Treatment with CH/PLA/MgONCs (10 mg/kg) showed a significant improvement in spatial and non-spatial memory functions. This was further supported by biochemical analysis showing improved antioxidant enzyme (GSH, SOD, CAT, and GPx activity) activities that significantly attenuated cholinergic activity and oxidative stress. In the CH/PLA/MgONCs-treated group, significant improvement was observed in the mitochondrial complex activity. ICV-STZ-induced neuroinflammation, as indicated by increased levels of TNF-α, IL-6, and CRP, was significantly reduced by CH/PLA/MgONCs treatment. Additionally, CH/PLA/MgONCs treated histological results showed improved healthy neuronal cells in the brain. Furthermore, in silico studies confirm that these molecules have good binding affinity and inhibit Aß aggregation. In conclusion, CH/PLA/MgONCs treatment reversed AD pathology by improving memory and reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. These findings recommend that CH/PLA/MgONCs are possible therapeutic agents to treat AD.

Gelatin/polyethylene glycol-loaded magnesium hydroxide nanocomposite to attenuate acetylcholinesterase, neurotoxicity, and activation of GPR55 protein in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease marked by mitochondrial dysfunction, amyloid-ß (Aß) aggregation, and neuronal cell loss. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for insulin receptors in diabetes therapy, but GPR55's role in AD is still unidentified. Gelatin (GE) and polyethylene glycol (PEG) polymeric hydrogels are commonly used in the drug delivery system. Therefore, the aim of the present study was the preparation of magnesium hydroxide nanocomposite using Clitoria ternatea (CT) flower extract, GE, and PEG (GE/PEG/Mg(OH)2NCs) by the green precipitation method. The synthesized GE/PEG/Mg(OH)2NCs were used to determine the effect of GPR55 activation of intracerebroventricular administration on streptozotocin (ICV-STC)-induced cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive deficits. The GE/PEG/Mg(OH)2NCs were administered following bilateral ICV-STC administration (3 mg/kg) in experimental rats. Neurobehavioral assessments were performed using a Morris water maze (MWM) and a passive avoidance test (PA). Cholinergic and antioxidant activity, oxidative stress, and mitochondrial complex activity were estimated in the cortex and hippocampus through biochemical analysis. Inflammatory markers (TNF-α, IL-6, and IL-1ß) were determined using the ELISA method. Our study results demonstrated that the GE/PEG/Mg(OH)2NCs treatment significantly improved spatial and non-spatial memory functions in behavioral studies. Moreover, the treatment with GE/PEG/Mg(OH)2NCs group significantly attenuated cholinergic dysfunction, oxidative stress, and inflammatory markers, and also highly improved anti-oxidant activity (GSH, SOD, CAT, and GPx) in the cortex and hippocampus regions. The western blot results suggest the activation of the GPR55 protein expression through GE/PEG/Mg(OH)2NCs. The histopathological studies showed clear cytoplasm and healthy neurons, effectively promoting neuronal activity. Furthermore, the molecular docking results demonstrated the binding affinity and potential interactions of the compounds with the AChE enzyme. In conclusion, the GE/PEG/Mg(OH)2NCs treated groups showed reduced neurotoxicity and have the potential as a therapeutic agent to effectively target AD.

Voglibose attenuates cognitive impairment, Aß aggregation, oxidative stress, and neuroinflammation in streptozotocin-induced Alzheimer's disease rat model.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease hallmarked by Amyloid-ß (Aß) aggregation, cognitive impairment, and neuronal and synaptic loss. In this study, AD was induced in male Wistar rats (n = 6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3 mg/kg/day), and Voglibose (Vog) was administered at various doses (10, 25, and 50 mg/kg), while Galantamine (3 mg/kg) acted as a reference standard drug. Behavioral alterations in both spatial and non-spatial memory functions were evaluated in the experimental rats. At the end of the study, all experimental rats were sacrificed, and their brain parts, the cortex and hippocampus, were subjected to biochemical, western blot, and histopathological analysis. In our study results, the statistically significant dose-dependent results from the behavioral tests show the Voglibose-treated groups significantly improved (p < 0.0001) spatial and non-spatial memory functions when compared with ICV-STZ-treated group. Meanwhile, when compared with ICV-STZ-treated rats, treatment with Voglibose (10, 25, and 50 mg/kg) showed the activities of both acetylcholinesterase (AChE) and malondialdehyde (MDA) were significantly attenuated (p < 0.0001), while the operation of antioxidant enzymes was considerably enhanced (p < 0.0001). The molecular estimation showed that it significantly attenuates (p < 0.0001) the TNF-α, IL-1ß, and CRP activity, and the western blot results demonstrate the significantly attenuated Aß aggregation. The histopathological results showed that the Voglibose treatment had an effective improvement in clear cytoplasm and healthy neuronal cells. In conclusion, our results suggest that Voglibose has potent neuroprotective effects against the ICV-STZ-induced AD model. Furthermore, these results support the possibility of Voglibose as a therapeutic approach to improving cognitive function, suggesting that controlling Aß aggregation might be a novel target for the development of AD.

Gelatin/polyvinyl alcohol loaded magnesium hydroxide nanocomposite attenuates neurotoxicity and oxidative stress in Alzheimer's disease induced rats.

Amyloid-ß (Aß) plaque formation, neuronal cell death, mitochondrial and cholinergic dysfunction are key indicators of Alzheimer's disease (AD). In this study, gelatin and polyvinyl alcohol (PVA) were tethered with magnesium hydroxide (Mg(OH)2) to synthesize nanocomposite (Ge/PVA/Mg(OH)2) through alkali co-precipitation. The characterization studies using FT-IR, XRD, DLS, and SEM-EDX confirmed the successful formation of Ge/PVA/Mg(OH)2 nanocomposite. Further, in vitro study it clearly demonstrated the impact of Ge/PVA/Mg(OH)2 nanocomposite on biocompatibility, cellular uptake, reduced Aß protein expression and protection of neuronal cell death. The confocal study further confirmed the down-regulation of Aß expression. The subsequent in vivo analysis witnessed the protective effect of Ge/PVA/Mg(OH)2 nanocomposites on the cognitive and synaptic impairments of AD in intraceribroventricular streptozotocin (ICV-STZ) treated rats. Oxidative stress, antioxidant enzymes, cholinergic and mitochondrial complex activity were conducted and revealed that the Acetylcholineesterase (AChE) and Malondialdehyde (MDA) activities were significantly decreased by contrast the antioxidant enzyme activities were found to be increased in the cortex and hippocampus regions of the brain. Thus, the present investigation recommends Ge/PVA/Mg(OH)2 nanocomposite to target AD and clinical translation.

Galantamine tethered hydrogel as a novel therapeutic target for streptozotocin-induced Alzheimer's disease in Wistar rats.

Amyloid-ß (Aß) plaque formation, neuronal cell death, and cognitive impairment are the unique symptoms of Alzheimer's disease (AD). No single step remedy is available to treat AD, so the present study aimed to improve the drugability and minimize the abnormal behavioral and biochemical activities in streptozotocin (STZ) induced AD experimental Wistar rats. In particular, we explored the utilization of methacrylated gelatin (GelMA), which is a biopolymeric hydrogel that mimics the natural tissue environment. The synthesized biopolymeric gel contained the drug galantamine (Gal). Investigations were conducted to evaluate the behavioral activities of STZ-induced AD experimental rats under STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal treatment. The experimental groups comprised the control and STZ, STZ â€‹+ â€‹GelMA, STZ â€‹+ â€‹Gal, and STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal (10 â€‹mg/kg) treated rats. Intracerebroventricular STZ ensures cognitive decline in terms of an increase in the escape latency period, with a decrease in the spontaneous alteration of behavioral activities. Our results indicated decrease Aß aggregation in the hydrogel-based drug treatment group and significant decreases in the levels of acetylcholinesterase and lipid peroxidation (p â€‹< â€‹0.001). In addition, the glutathione and superoxide dismutase activities appeared to be improved in the STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal group compared with the other treatment groups. Furthermore, histopathological and immunohistochemical experiments showed that the GelMA â€‹+ â€‹Gal treated AD rats exhibited significantly improved behavioral and biochemical activities compared with the STZ treated AD rats. Therefore, STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal administration from the pre-plaque stage may have a potential clinical application in the prevention of AD. Thus, we conclude that hydrogel-based Gal drugs are efficient at decreasing Aß aggregation and improving the neuroinflammatory process, antioxidant activity, and neuronal growth.

Vermiremediation of engine oil contaminated soil employing indigenous earthworms, Drawida modesta and Lampito mauritii.

Engine oil consists of hazardous substances that adversely affect the environment and soil quality. Bioremediation (employing organisms) is an appropriate technique to mitigate engine oil pollution. In the present study, the earthworm species, Drawida modesta (epigeic) and Lampito mauritii (anecic) were used to restore the soil polluted with polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs) from used engine oil. Four treatments were set up in addition to positive and negative controls. A maximum of 68.6% PAHs and 34.3% TPHs removal in the treatment with soil (1 kg), cow dung (50 g), used engine oil (7.5 mL) and earthworms was recorded after 60 days. Undoubtedly, earthworms effectively removed PAHs and TPHs from the oil-contaminated soil. PAHs were more strongly accumulated in D. modesta (16.25 mg kg-1) than in L. mauritii (13.25 mg kg-1). Further, histological analysis revealed the epidermal surface irregularity, cellular disintegration, and cellular debris in earthworms. The pH (6.3%), electrical conductivity (12.7%), and total organic carbon (35.4%) were significantly (at P < 0.05) decreased after 60 days; while, total nitrogen (62%), total potassium (76.2%), and total phosphorus (19.2%) were substantially increased at the end of the experiment. The seed germination assay with fenugreek indicates that germination percentage (95%), and germination index (179), were dramatically increased in earthworm inoculated treatments when compared to the negative control (without earthworms). The results reveal that there is a great scope for utilizing the earthworms, D. modesta and L. mauritii for the bioremediation of soils contaminated with PAHs and TPHs.

Activation of biochar through exoenzymes prompted by earthworms for vermibiochar production: A viable resource recovery option for heavy metal contaminated soils and water.

The industrial revolution and indiscriminate usage of a wide spectrum of agrochemicals account for the dumping of heavy metals in the environment. In-situ/ex-situ physical, chemical, and bioremediation strategies with pros and cons have been adopted for recovering metal contaminated soils and water. Therefore, there is an urgent requirement for a cost-effective and environment-friendly technique to combat metal pollution. Biochar combined with earthworms and vermifiltration is a suitable emerging technique for the remediation of metal-polluted soils and water. The chemical substances (e.g., sodium hydroxide, zinc chloride, potassium hydroxide, and phosphoric acid) have been used to activate biochar, which also faces several shortcomings. Studies reveal that extracellular enzymes have been used to activate biochar which is produced by earthworms and microbes that can alter the surface of the biochar. The present review focuses on the global scenario of metal pollution and its remediation through biochar activation using earthworms. The earthworms and biochar can produce "vermibiochar" which is capable of reducing the metal ions from contaminated water and soils. The vermifiltration can be a suitable technology for metal removal from wastewater/effluent. Thus, the biochar has a trick of producing entirely new options at a time when vermifiltration and other technologies are least expected. Further attention to the biochar-assisted vermifiltration of different sources of wastewater is required to be explored for the large-scale utilization of the process.

Cleaner production of agriculturally valuable benignant materials from industry generated bio-wastes: A review.

Bio-wastes from different agro-based industries are increasing at a rapid rate with the growing human population's demand for the products. The industries procure raw materials largely from agriculture, finish it with the required major product, and produce huge bio-wastes which are mostly disposed unscientifically. This creates serious environmental problems and loss of resources and nutrients. Traditional bio-wastes disposal possess several demerits which again return with negative impact over the eco-system. Anaerobic digestion, composting, co-composting, and vermicomposting are now-a-days given importance due to the improved and modified methods with enhanced transformation of bio-wastes into suitable soil amendments. The advanced and modified methods like biochar assisted composting and vermicomposting is highlighted with the updated knowledge in the field. Hence, the present study has been carried to compile the effective and efficient methods of utilizing industry generated bio-wastes for circularity between agriculture - industrial sectors to promote sustainability.

Centrality of cattle solid wastes in vermicomposting technology - A cleaner resource recovery and biowaste recycling option for agricultural and environmental sustainability.

The current review reports the importance and significance of cattle solid waste in vermicomposting technology concerning biowaste pollution in the environment. Needy increasing population evokes livestock production resulting in the massive generation of livestock wastes, especially cattle dung. Improper disposal and handling of biowastes originating from agriculture, industries, forests, rural and urban areas lead to nutrient loss, environmental pollution and health risks. Among the organic waste disposal methods available, vermicomposting is regarded as an environmentally friendly technology for bioconversion of agricultural, industrial, rural and urban generated organic solid wastes which are serving as reservoirs of environmental pollution. In vermicomposting of organic wastes, cattle dung plays a central role in mineralization, nutrient recovery, earthworm and microbial activity leading to vermifertilizer production. Even though the vermicomposting studies use cattle dung invariably as an amendment material, its importance has not been reviewed to highlight its central role. Hence, the present review mainly emphasizes the key role played by cattle dung in vermicomposting. Vermiconversion of cattle dung alone and in combination with other biowaste materials of environmental concern, mechanisms involved and benefits of vermicompost in sustainable agriculture are the major objectives addressed in the present review. The analysis reveals that cattle dung is indispensable amendment material for vermicomposting technology to ensure agricultural and environmental sustainability by reducing pollution risks associated with biowastes on one hand, and nutrient-rich benign vermifertilizer production on the other hand.

Metallothionein dependent-detoxification of heavy metals in the agricultural field soil of industrial area: Earthworm as field experimental model system.

Earthworms are known to reclaim soil contamination and maintain soil health. In the present study, the concentration of DTPA extractable heavy metals, Cd, Cu, Cr, Pb, and Zn in vermicasts and tissues of the earthworms (anecic: Lampito mauritii; epigeic: Drawida sulcata) collected from the soils of four different industrial sites, Site-I (Sago industry), Site-II (Chemplast industry), Site-III (Dairy industry) and Site-IV (Dye industry) have been studied. The heavy metals in industrial soils recorded were 0.01-326.42 mg kg-1 with higher Cu, Cr, and Zn contents while the vermicasts showed lower heavy metal loads with improved physicochemical properties and elevated humic substances. The higher humic substances dramatically decreased the heavy metals in the soil. The bioaccumulation factors of heavy metals (mg kg-1) are in the order: Zn (54.50) > Cu (17.43) > Cr (4.54) > Pb (2.24) > Cd (2.12). The greatest amount of metallothionein protein (nmol g-1) was recorded in earthworms from Site-IV (386.76) followed by Site-III (322.14), Site-II (245.82), and Site-I (232.21). Drawida sulcata can produce a considerable amount of metallothionein protein than Lampito mauritii as the metallothionein production is dependent upon the presence of pollutants. The molecular docking analysis indicates a binding score of 980 for Cd, Cr and Cu, and 372 for Zn. Pb may bind with a non-metallothionein protein of earthworms and bio-accumulated in the internal chloragogenous tissues. Metallothionein neutralizes the metal toxicity and controls the ingestion of essential elements.

Earthworm intervened nutrient recovery and greener production of vermicompost from Ipomoea staphylina - An invasive weed with emerging environmental challenges.

The invasive weed, Ipomoea staphylina (IS) with cow dung (CD) and mushroom spent straw (MS) in four different combinations (IS:CD:MS), V1 (1:1:0), V2 (2:1:1), V3 (1:0:1) and V4 (1:1:1) were pre-decomposed for 21 days followed by 50 days vermicomposting using Eudrilus eugeniae in triplicates in order to alleviate and to utilize the weed biomass in an environment-friendly manner. The contents of organic matter, organic carbon, cellulose, lignin, C/N and C/P ratios showed a decrease, while electrical conductivity, total NPK, calcium, sodium, and nitrate-nitrogen showed a significant increase in vermicompost over control. Water-soluble organic carbon to organic nitrogen ratio and C/N ratio in V1 (0.52 and 17.55) and V4 (0.43 and 16.56), respectively, were in conformity with the maturity of vermicomposts. Scanning electron micrographs of the end products clearly showed more fragmented, fine, and porous particles in vermicompost. Copper, chromium, cadmium, lead, and zinc in vermicomposts were below the permissible limits. Dehydrogenase, acid phosphatase, alkaline phosphatase, cellulase, and protease activities were significantly higher in V4 than other treatments, implying the role of MS and CD addition during vermicomposting. Though V3 combination supported worm biomass, V4 combination was found to favor the fecundity of Eudrilus eugeniae. Results reveal that 1:1:1 combination of SI + CD + MS (V4) is suitable for utilizing the weed biomass for vermicompost production and nutrient recovery. From the biomass of environmentally problematic weed, Ipomoea staphylina, nutrient-rich vermicompost can be produced through vermitechnology for sustainable environmental management and agriculture.

Enriched pressmud vermicompost production with green manure plants using Eudrilus eugeniae.

Vermicomposting of pressmud with cow dung and nitrogenous green manures (Gliricidia sepium and Leucaena leucocephala) was carried out using Eudrilus eugeniae (50 days). The reduction in pH, total organic carbon, C/N ratio, water-soluble organic carbon (Cws)/Norg and C/P ratios, and a pronounced increase in NPK contents and microbial population in vermicompost were observed. An enhanced TKN of 3.80% and 3.45% was recorded in vermicomposts of pressmud + cow dung + L. leucocephala (2:1:1) and pressmud + cow dung + G. sepium (2:1:1) respectively. The C/N and Cws/Norg ratios in vermicompost ranged from 11.86 to 16.66 and 0.53 to 1.33, respectively. The activity of dehydrogenase, urease, acid and alkaline phosphatase declined towards the end, indicating the progression of vermicompost maturity. The pressmud and green manure substrates promoted more biomass of E. eugeniae, while cow dung with green manure combination favored reproduction. The amendment of cow dung and green manure plants to pressmud (2:1:1 ratio) results in nutrient-enriched vermicompost production.

Environment-friendly management of textile mill wastewater sludge using epigeic earthworms: Bioaccumulation of heavy metals and metallothionein production.

In the present study, Eudrilus eugeniae and Perionyx excavatus were used for vermistabilization of textile mill sludge in different combinations with cowdung for 60 days. A higher percentage of metal removal was observed in earthworm treated mixtures for cadmium (54.5%) followed by copper (36.0%), chromium (37.0%) and zinc (35.9%). Vermistabilized textile mill sludge + cowdung (1:1) showed a maximum percentage increase in total NPK, a significant (P < 0.05) increase in bacteria, fungi, and actinomycetes with a better earthworm survival rate. A higher amount of metallothionein protein was produced by E. eugeniae than P. excavatus. Further, 100% textile mill sludge showed a number of histological abnormalities like degeneration of cells, cellular debris, and uneven cellular compartmentation while textile mill sludge with cowdung showed normal earthworm histology. Results suggest that textile mill sludge + cowdung (1:1) combination is suitable for vermistabilization of textile mill sludge.

Studies on the toxic effects of agrochemical pesticide (Monocrotophos) on physiological and reproductive behavior of indigenous and exotic earthworm species.

Earthworms are an ideal biological model in toxicity assays and environmental monitoring studies. In the present study, the reproductive toxicity and histopathological effects of Monocrotophos pesticide on an exotic epigeic Eudrilus eugeniae and an indigenous epigeic Perionyx barotensis earthworm were studied. Earthworm species were exposed to different concentrations of pesticide like 450 ppm, 500 ppm, and 650 ppm for 45 days and the mortality rate and reproductive activity was recorded every 15 days of exposure. There was an increase in mortality and abnormal sperm (asthenospermia, necrospermia, and oligospermia) and defective cocoons in earthworms with increasing concentrations of the pesticide. Histopathological changes like rupture of chloragogenous tissue, longitudinal muscle, fused and extra-villous growth and necrotic cell rupture in earthworm's body wall (epidermis, circular and longitudinal muscles) were observed. Fluorescent probes have detected cell death in pesticide-treated earthworms when compared to the control group after 45 days. The present findings show that Monocrotophos pesticide on exposure to epigeic earthworm species causes significant reproductive toxicity and histopathological abnormalities and these changes could be used as a tool in environmental risk assessment of pesticides.Abbreviations: DDT: Dichlorodiphenyltrichloroethane; MCP: Monocrotophos; EPA: Environment Protection Act; SL: Soluble Liquid; C: N (Carbon: Nitrogen); C: P (Carbon: Phosphorus); LC: Lethal Concentration; PBS: Phosphate Buffer Solution; WHO: World Health Organization; H&E: Hematoxylin and Eosin; SV: seminal vesicles; O: ovary; GP: genital papillae; Ch: chloragogenous tissue; EL: epithelial layer; CM: circular muscle; LM: longitudinal muscle; CD: cell debris.

Drug-Carrying Capacity and Anticancer Effect of the Folic Acid- and Berberine-Loaded Silver Nanomaterial To Regulate the AKT-ERK Pathway in Breast Cancer.

Currently, in clinics, breast cancer is treated with free chemotherapeutic drugs, as a result there is not much therapeutic effect in treated models, leading to substantial systemic toxicity. To overcome these critical problems for the primary outcome, we developed the formulated nanomaterial (FA-PEG@BBR-AgNPs) aimed to specifically target cancer cells via nanoscopic-based drug delivery for getting better therapeutic effectiveness. In the present study, an isoquinoline alkaloid, berberine (BBR), was chosen as a cancer therapeutic agent, encapsulated on citrate-capped silver nanoparticles (AgNPs) through electrostatic interactions (BBR-AgNPs). Then, BBR-AgNPs were conjugated with polyethylene glycol-functionalized folic acid (FA-PEG) via hydrogen bonding interactions (FA-PEG@BBR-AgNPs). The transmission electron microscopy study shows the cellular invasion of the formulated FA-PEG@BBR-AgNPs, indicating the accretion of the nanomaterial at the tumor-specific site. Hence, FA conjugated with the nanomaterial suggests an efficient release of BBR molecules into the specific cancer site. Consequently, the results showed an increase in apoptotic induction via reactive oxygen species and condensed nuclei in cancer cells. Moreover, the western blotting analysis shows reduced/increased expression of PI3K, AKT, Ras, Raf, ERK, VEGF, HIF1α, Bcl-2, Bax, cytochrome c, caspase-9, and caspase-3, thereby enhancing apoptosis. Likewise, the in vivo antitumor efficiency of FA-PEG@BBR-AgNPs showed a significant restraint of tumor progression, and histopathological observations of lung, liver, kidney, heart, and brain tissues proved lesser toxicity of FA-PEG@BBR-AgNPs. Thus, the successfully formulated nanomaterial can serve as a potential drug-discharging vehicle to combat cancer cells by a molecular-based targeting approach.

Protective effect of Triphala on cold stress-induced behavioral and biochemical abnormalities in rats.

Stress is one of the basic factors in the etiology of number of diseases. Cold-stress occurs when the surrounding temperature drops below 18 degrees C, the body may not be able to warm itself, and hence serious cold-related illnesses, permanent tissue damage and death may results. The present study was aimed to investigate the effect of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) against the cold stress-induced alterations in the behavioral and biochemical abnormalities in four different groups (saline control, Triphala, cold-stress and Triphala with cold-stress) of Wistar strain albino rats. In this study cold-stress (8 degrees C for 16 h/d/15 days) was applied and the oxidative stress was assessed by measuring the extent of lipid peroxidation (LPO) and the changes in corticosterone levels. Upon exposure to the cold-stress, a significant (P<0.05) increase in immobilization with decrease in rearing, grooming, and ambulation behavior was seen in open field. Following cold-exposure, significant increase in the LPO and corticosterone levels was observed. Oral administration of Triphala (1 g/kg/animal body weight) for 48 days significantly prevented these cold stress-induced behavioral and biochemical abnormalities in albino rats. The results of this study suggest that Triphala supplementation can be regarded as a protective drug against stress.