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.

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.

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.

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.

Ligand-conjugated mesoporous silica nanorattles based on enzyme targeted prodrug delivery system for effective lung cancer therapy.

Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA2α activity, arachidonic acid release and cell proliferation were considerably reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems.

A correlation of fecal volatiles and steroid hormone profiles with behavioral expression during estrous cycle of goat, Capra hircus.

Chemical signals (both volatile and non-volatile) form the major communication channels in animals. These signals are transferred mainly through excretory sources to facilitate inter-individual communication. In particular, the reproductive cycle of female mammals, including goats, exhibits significant changes in the constituents of their excretory products, and female mammals also express different behavioral patterns. We propose that feces is one of the important sources of chemo-signals in goats. However, the behavioral patterns and analysis of excretory sources based on chemical communication have not yet been studied in the Indian goat, Capra hircus. To validate our hypothesis, we analyzed the behavioral patterns and the volatiles and steroid hormone profiles in the feces samples of female goats during the estrous cycle. Here, we synchronized the estrous cycle in six female goats and obtained feces samples. The samples were extracted with dichloromethane and analyzed using gas chromatography-mass spectrometry. A portion of the sample was used for hormone assay to confirm the phases in the estrous cycle. Induction of she-goats into estrus was detected from the vaginal swelling, mucus discharge, restlessness, reduced milk secretion, bellowing, bleating, frequent urination, standing heat, allowing the male to mount, mounting on other females and teasing of males. The repeated male behaviors viz., flehmen, mounting, penile protrusion, body rubbing, dominance over other males and finally coitus with estrus female by male goats were observed. Analysis of volatiles revealed a total of twenty-four compounds combining all the phases in the estrous cycle. Among those, some of the volatile compounds and two antioxidants (ascorbic acid and vitamin E) were estrus-specific. Based on the fecal steroid analysis, higher level of estradiol during estrus and higher level of progesterone during post-estrus were observed. The behavioral patterns of female and male goats combined with qualitative differences in the volatile compounds and the two antioxidants rendered the estrus identifiable. Furthermore, the fecal steroid analysis also supported the detection of hormonal status during the estrous cycle. To the best of our knowledge, this is the first report correlating the behavior with volatiles and hormones in the feces samples from female Indian goats. It is concluded that the volatile pattern and hormone profile in feces, supported by specific behavioral patterns, should be considered a better modality of non-invasive estrus detection in goats.

Response of male mice to odours of female mice in different stages of oestrous cycle: self-grooming behaviour and the effect of castration.

The behavioural assays were carried out in a Y-maze wherein intact, castrated and testosterone-treated male mice were exposed to oestrus and non-oestrus urine samples. The intact male mice investigated more frequently and spent more time in the Y-maze arm with oestrus urine than in that with non-oestrus urine. In contrast, the castrated mice were not attracted to oestrus urine, whereas testosterone-treated mice showed preference for oestrus urine. The rate of self-grooming was higher in intact males in case of exposure to oestrus urine while the rate was lower with respect to non-oestrus urine. However, castrated mice exhibited less self-grooming behaviour which was partially restored by testosterone treatment. The results suggest that self-grooming behaviour is an indicator of detection and discrimination of oestrus by males, and supports the androgen role in male chemosensory ability to discriminate between oestrus and non-oestrus female odours.

Antioxidant and in vitro anticancer effect of 2-pyrrolidinone rich fraction of Brassica oleracea var. capitata through induction of apoptosis in human cancer cells.

The aim of this study was to analyze if the 2-pyrrolidinone rich fraction of Brassica oleracea var. capitata exhibiting antioxidant and in vitro anticancer activities. 2-Pyrrolidinone is an active compound present in Brassica oleracea var. capitata. Our findings explored the potential use of 2-pyrrolidinone in cancer treatment. This compound was identified and isolated by gas chromatography-mass spectrometry and high-performance liquid chromatography from the leaf of Brassica oleracea var. capitata. The resultant rich active compound exhibited in vitro cytotoxicity in HeLa and PC-3 human cancer cell lines, and it also exhibited antioxidant activity in cell free assays. DAPI staining, an apoptotic analysis and cell cycle analysis were performed to evaluate the anticancer activity of 2-pyrrolidinone against the above cell lines. The IC50 value of 2-pyrrolidinone was determined to be of 2.5 µg/ml for HeLa, 3 µg/ml for PC-3 cells at 24 h and 1.5 µg/ml for HeLa and 2 µg/ml for PC-3 cells at 48 h, respectively. However, cell cycle analysis revealed that the anti-proliferative effects of the 2-pyrrolidinone were mediated through cell cycle arrest in the G0/G1 phase. These results from the current study suggest that the 2-pyrrolidinone have potential anticancer effects, which will lead to the development of new anticancer agents for arresting cancer cells growth in vitro.

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.

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.

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.

Label-Free Electrochemical Detection of the Cancer Biomarker Platelet-Derived Growth Factor Receptor in Human Serum and Cancer Cells.

Overexpression of the platelet-derived growth factor receptor (PDGFR) was already associated with the loss of p53 function as cancer progresses in lung, breast, and cervical cancers. Cancer biomarker detection has faced challenges and barriers due to various limitations, including a high limit of detection, low sensitivity, time-consuming techniques, and expensive equipment. Hence, the present investigation is designed to develop a cost-effective novel biosensor based on a charge-based affinity bait molecule to detect the PDGFR, thus overcoming the limitations and challenges with an immune technique based on antigen-antibody interactions. We employed EDC-NHS coupling between poly (diallyl dimethylammonium chloride) and poly(acrylic acid) to attach the multiwall carbon nanotube surface. As a result, we performed electrochemical PDGFR conversion sensing with a dynamic range of 1-10,000 ng/mL and a detection limit of 1.5 pg/mL, which is comparable to the best current results. The biosensor also displayed good selectivity, 2.51% repeatability (RSD, n = 5), and 30 days of stability. Our study provides a pathway for the design of diagnostic interfaces in biosystems, as well as the emergence of new sensor types based on ligand-receptor interactions.

Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism.

The ATP-sensitive potassium (K(ATP)) channel controls insulin secretion by coupling glucose metabolism to excitability of the pancreatic beta-cell membrane. The channel comprises four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by KCNJ11 and ABCC8, respectively. Mutations in these genes that result in reduced activity or expression of K(ATP) channels lead to enhanced beta-cell excitability, insulin hypersecretion and hypoglycaemia, and in humans lead to the clinical condition congenital hyperinsulinism (CHI). Here we have investigated the molecular basis of the focal form of CHI caused by one such mutation in Kir6.2, E282K. The study led to the discovery that Kir6.2 contains a di-acidic ER exit signal, (280)DLE(282), which promotes concentration of the channel into COPII-enriched ER exit sites prior to ER export via a process that requires Sar1-GTPase. The E282K mutation abrogates the exit signal, and thereby prevents the ER export and surface expression of the channel. When co-expressed, the mutant subunit was able to associate with the wild-type Kir6.2 and form functional channels. Thus unlike most mutations, the E282K mutation does not cause protein mis-folding. Since in focal CHI, maternal chromosome containing the K(ATP) channel genes is lost, beta-cells of the patient would lack wild-type Kir6.2 to rescue the mutant Kir6.2 subunit expressed from the paternal chromosome. The resultant absence of functional K(ATP) channels leads to insulin hypersecretion. Taken together, we conclude that surface expression of K(ATP) channels is critically dependent on the Sar1-GTPase-dependent ER exit mechanism and abrogation of the di-acidic ER exit signal leads to CHI.

Properties of mouse vomeronasal receptor and assessment of its role in pheromone signalling.

Vomeronasal type 2 receptor (V2Rx) from Swiss mouse (Mus musculus (L.)) was analyzed by high-resolution ion-exchange chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), Ion Spray tandem mass spectrometry (MS/MS), 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 1-aminoanthracene (1-AMA) fluorometric assay. Vomeronasal sensory neuronal cell bound proteins were resolved into major protein peaks. Several proteins were identified and subsequently purified as the V2Rx receptor on 10% SDS-PAGE with trace amounts of other protein bands. The molecular weight of the identified V2Rx was 109 kDa. MALDI-TOF and micro-sequencing experiments demonstrated that the identified V2Rx receptor shared considerable sequence similarity with vomeronasal receptor type 2 (NCBI Accession Number AB267725), which is a seven transmembrane peptide with 912 amino acid residues. The molecular characterization revealed that the N-terminus of the V2Rx receptor contained the 11GAEAAE16 domain involved in pheromone signalling. The biometric assay (octanamine-V2Rx binding) showed the identified V2Rx receptor and mouse sex pheromone to 2-octanamine (methyl heptyl) in a 1:1 ratio. Uptake of odourants determined in physiological condition showed enhanced V2Rx receptors as volatile hydrophobic pheromone receptors in the vomeronasal neuron of the Swiss mouse.

Biochemical analysis of female mice urine with reference to endocrine function: a key tool for estrus detection.

Species-specific chemical signals released through urine, sweat, saliva and feces are involved in communication between animals. Urinary biochemical constituents along with pheromones may contribute to variation across reproductive cycles and facilitate to estrus detection. Hence, the present study was designed to analyze such biochemical profiles, such as proteins, carbohydrates, lipids, fatty acids, in response with steroid hormones such as estradiol and progesterone. The experimental groups were normal, prepubertal, ovariectomized, and ovariectomized with estrogentreated female mice. In normal mice, the protein and lipid concentrations in urine were significantly higher in proestrus and estrus phases and the quantity of fatty acids was also comparatively higher in estrus. Furthermore, certain fatty acids, namely tridecanoic, palmitic and oleic acids, were present during proestrus and estrus phases, but were exclusively absent in ovariectomized mice. However, the carbohydrate level was equally maintained throughout the four phases of estrous cycle. For successful communication, higher concentrations of protein and specific fatty acids in estrus are directly involved. The significant increase in estradiol at estrus and progesterone at metestrus seems to be of greater importance in the expression pattern of biochemical constituents and may play a notable role in estrous cycle regulation. Thus, we conclude that the variations observed in the concentration of the biochemical constituents depend on the phase of the reproductive cycle as well as hormonal status of animals. The appearance of protein and specific fatty acids during estrus phase raises the possibility to use these as a urinary indicators for estrus detection.

Phyto-drug conjugated nanomaterials enhance apoptotic activity in cancer.

Cancer continues to be one of the leading causes of death worldwide and is a major obstacle to increased life expectancy. However, survival has not improved significantly with average cancer standard treatment strategies over the past few decades; survival rates have remained low, with tumor metastasis, adverse drug reactions, and drug resistance. Therefore, substitute therapies are essential to treat this dreadful disease. Recently, research has shown that natural compounds in plants, such as phytochemicals, are extensively exploited for their anticarcinogenic potential. Phytochemicals may show their anticancer activity different cancer cell markers may alter molecular pathways, which promote in cellular events such as cell cycle arrest and apoptosis, regulate antioxidant status, cell proliferation, migration, invasion and toxicity. Although their outstanding anticancer activity, however, their pharmacological budding is hindered by their low aqueous solubility, poor bioavailability, and poor penetration into cells, hepatic disposition, narrow therapeutic index, and rapid uptake by normal tissues. In this situation, nanotechnology has developed novel inventions to increase the potential use of phytochemicals in anticancer therapy. Nanoparticles can improve the solubility and stability of phytochemicals, specific tumor cell/tissue targeting, enhanced cellular uptake, reduction of phytochemicals. Therapeutic doses of phytochemicals for a long time. Additional benefits include better blood stability, multifunctional design of nanocarriers and improvement in countermeasures. This review summarizes the advances in the use of nanoparticles for the treatment of cancer, as well as various nano-drug deliveries of phytochemicals against cancer. In particular, we are introducing several applications of nanoparticles in combination with phyto-drug for the treatment of cancer.

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.

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.

Induction of intrinsic apoptotic signaling pathway in A549 lung cancer cells using silver nanoparticles from Gossypium hirsutum and evaluation of in vivo toxicity.

In the past decade, the research communities raised wide concerns on using medicinal plants for synthesis of nanomaterials due to its effective biological activity, lower side effects and also eco-friendly manner. Our previous report concentrated on the biomedical efficacy of fine characterized silver nanoparticles (AgNPs) from Gossypium hirsutum (cotton) leaf extract. Further, the current examination is planned to reveal the molecular mechanisms involving for activation of mitochondria-mediated signaling pathway by AgNPs in human lung cancer cells (A549) using various biological endpoints such as apoptotic induction by HOECHST 33342, AO/EtBr and Rhodamine 123 staining, cell cycle analysis using flow cytometry, gene and protein expressions by RT-PCR and immunoblotting respectively. This study was further extended to identify the toxicity of AgNPs using an animal model. Interestingly, we observed that A549 cells treated with AgNPs resulted in G2/M arrest and ultimately leads to induction of apoptosis cell death. Moreover, gene analysis demonstrated that diminished expression of anti-apoptotic (Bcl-2) and enhanced expression of pro-apoptotic (Bax) mitochondrial genes. The alterations in the gene pattern may interrupt of mitochondrial membrane potential which facilitates the releasing of cytochrome c (cyt c) into cytosol. The cyt c act as a key molecule for activation of caspases (9 and 3) to initiate intrinsic apoptotic signaling cell death process. The histological analysis proven the application of AgNPs in nanomedicine is quietly harmless and would not cause any discernible stress like swelling and inflammation to the organs of mice. Taken together, this investigation may provide solid evidence for cotton crop mediated AgNPs induced apoptosis cell death pathway and offer a novel approach for cancer therapy.

Gelatin-polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics.

Gelatin is a promising material as scaffold with therapeutic and regenerative characteristics due to its chemical similarities to the extracellular matrix (ECM) in the native tissues, biocompatibility, biodegradability, low antigenicity, cost-effectiveness, abundance, and accessible functional groups that allow facile chemical modifications with other biomaterials or biomolecules. Despite the advantages of gelatin, poor mechanical properties, sensitivity to enzymatic degradation, high viscosity, and reduced solubility in concentrated aqueous media have limited its applications and encouraged the development of gelatin-based composite hydrogels. The drawbacks of gelatin may be surmounted by synergistically combining it with a wide range of polysaccharides. The addition of polysaccharides to gelatin is advantageous in mimicking the ECM, which largely contains proteoglycans or glycoproteins. Moreover, gelatin-polysaccharide biomaterials benefit from mechanical resilience, high stability, low thermal expansion, improved hydrophilicity, biocompatibility, antimicrobial and anti-inflammatory properties, and wound healing potential. Here, we discuss how combining gelatin and polysaccharides provides a promising approach for developing superior therapeutic biomaterials. We review gelatin-polysaccharides scaffolds and their applications in cell culture and tissue engineering, providing an outlook for the future of this family of biomaterials as advanced natural therapeutics.