Anti-tuberculosis drugs used in a directly observed treatment short course (DOTS) schedule alter endocrine patterns and reduce the ovarian reserve and oocyte quality in the mouse.

CONTEXT: Tuberculosis is one of the major infectious diseases, with people of reproductive age group having a high risk of infection. AIMS: The present study was designed to understand the consequences of anti-tuberculosis drugs (ATDs) used in DOTS (directly observed treatment short course) schedule on ovarian function. METHODS: Adult female Swiss albino mice were orally administered with combinations of ATDs used in the DOTS schedule every day for 4weeks. At 2weeks after the cessation of ATDs administration, the endocrine changes and ovarian function were assessed in mice. KEY RESULTS: Administration of ATDs to mice resulted in a prolonged estrous cycle, reduced ovarian follicle reserve, alteration in FSH, LH, and progesterone level, and decreased the number of ovulated oocytes. Further, the degree of fragmentation, degeneration, abnormal distribution of cytoplasmic organelles, abnormal spindle organisation, and chromosomal misalignment were higher in oocytes that were ovulated following superovulation. Blastocysts derived from ATDs treated mice had significantly lower total cell numbers and greater DNA damage. A marginal increase in the number of resorbed fetuses was observed in all the ATDs treated groups except in the multidrug resistance treatment group. Male progeny of ATDs treated mice had decreased sperm count and lower progressive motility, while female progeny exhibited a non-significant reduction in the number of oocytes ovulated. CONCLUSIONS: Theresults of this study suggest that ATDs can have significant adverse effects on the ovarian reserve, cytoplasmic organisation of oocytes, and can potentially cause transgenerational changes. IMPLICATIONS: The findings of the present study indicate ovarian toxicity of ATDs and warrant further research in the direction of identifying alternate drugs with minimal toxicity, and strategies to mitigate the ovarian toxicity induced by these drugs.

Hsp70 overexpression in Drosophila hemocytes attenuates benzene-induced immune and developmental toxicity via regulating ROS/JNK signaling pathway.

Benzene, a ubiquitous environmental chemical, is known to cause immune dysfunction and developmental defects. This study aims to investigate the relation between benzene-induced immune dysfunction and developmental toxicity in a genetically tractable animal model, Drosophila melanogaster. Further, the study explored the protective role of Heat Shock Protein 70 (Hsp70) against benzene-induced immunotoxicity and subsequent developmental impact. Drosophila larvae exposed to benzene (1.0, 10.0, and 100.0 mM) were examined for total hemocyte (immune cells) count, phagocytic activity, oxidative stress, apoptosis, and their developmental delay and reduction were analyzed. Benzene exposure for 48 h reduced the total hemocytes count and phagocytic activity, along with an increase in the Reactive Oxygen Species (ROS), and lipid peroxidation in the larval hemocytes. Subsequently, JNK-dependent activation of the apoptosis (Caspase-3 dependent) was also observed. During their development, benzene exposure to Drosophila larvae led to 3 days of delay in development, and ~40% reduced adult emergence. Hsp70-overexpression in hemocytes was found to mitigate benzene-induced oxidative stress and abrogated the JNK-mediated apoptosis in hemocytes, thus restoring total hemocyte count and improving phagocytotic activity. Further, hsp70-overexpression in hemocytes also lessened the benzene-induced developmental delay (rescue of 2.5 days) and improved adult emergence (~20%) emergence, revealing a possible control of immune cells on the organism's development and survival. Overall, this study established that hsp70-overexpression in the Drosophila hemocytes confers protection against benzene-induced immune injury via regulating the ROS/JNK signaling pathway, which helps in the organism's survival and development.

2,5-Bis(2,2,2-trifluoroethoxy)phenyl-tethered 1,3,4-Oxadiazoles Derivatives: Synthesis, In Silico Studies, and Biological Assessment as Potential Candidates for Anti-Cancer and Anti-Diabetic Agent.

In the present work, a series of new 1-{5-[2,5-bis(2,2,2-trifluoroethoxy)phenyl]-1,3,4-oxadiazol-3-acetyl-2-aryl-2H/methyl derivatives were synthesized through a multistep reaction sequence. The compounds were synthesized by the condensation of various aldehydes and acetophenones with the laboratory-synthesized acid hydrazide, which afforded the Schiff's bases. Cyclization of the Schiff bases yielded 1,3,4-oxadiazole derivatives. By spectral analysis, the structures of the newly synthesized compounds were elucidated, and further, their anti-cancer and anti-diabetic properties were investigated. To examine the dynamic behavior of the candidates at the binding site of the protein, molecular docking experiments on the synthesized compounds were performed, followed by a molecular dynamic simulation. ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) prediction revealed that most of the synthesized compounds follow Lipinski's rule of 5. The results were further correlated with biological studies. Using a cytotoxic assay, the newly synthesized 1,3,4-Oxadiazoles were screened for their in vitro cytotoxic efficacy against the LN229 Glioblastoma cell line. From the cytotoxic assay, the compounds 5b, 5d, and 5m were taken for colony formation assay and tunnel assay have shown significant cell apoptosis by damaging the DNA of cancer cells. The in vivo studies using a genetically modified diabetic model, Drosophila melanogaster, indicated that compounds 5d and 5f have better anti-diabetic activity among the different synthesized compounds. These compounds lowered the glucose levels significantly in the tested model.

Medicinal plants in mitigating electromagnetic radiation-induced neuronal damage: a concise review.

Although the evidence is inconclusive, epidemiological studies strongly suggest that increased exposure to electromagnetic radiation (EMR) increases the risk of brain tumors, parotid gland tumors, and seminoma. The International Agency for Research on Cancer (IARC) has classified mobile phone radiofrequency radiation as possibly carcinogenic to humans (Group 2B). Humans being are inadvertently being exposed to EMR as its prevalence increases, mainly through mobile phones. Radiation exposure is unavoidable in the current context, with mobile phones being an inevitable necessity. Prudent usage of medicinal plants with a long history of mention in traditional and folklore medicine and, more importantly, are safe, inexpensive, and easily acceptable for long-term human use would be an appealing and viable option for mitigating the deleterious effects of EMR. Plants with free radical scavenging, anti-oxidant and immunomodulatory properties are beneficial in maintaining salubrious health. Green tea polyphenols, Ginkgo biloba, lotus seedpod procyanidins, garlic extract, Loranthus longiflorus, Curcuma amada, and Rosmarinus officinalis have all been shown to confer neuroprotective effects in validated experimental models of study. The purpose of this review is to compile for the first time the protective effects of these plants against mobile phone-induced neuronal damage, as well as to highlight the various mechanisms of action that are elicited to invoke the beneficial effects.

Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice.

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.

Synthesis of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives as potential glucosidase inhibitors.

BACKGROUND: A hybrid molecule of different biologically active substances can improve affinity and efficiency compared to a standard drug. Hence based on this fact, we predict that a combination of fluorine, oxadiazole, sulfur, etc., may enhance α-glucosidase inhibition activity compared to a standard drug. METHODS: A series of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives (2a-2i) were synthesized and characterized using spectroscopic techniques such as 1HNMR and LC-MS. In order to evaluate its bioactivity, in vitro α-amylase and α-glycosidase inhibitory activity were performed. In vivo study was carried using a genetic model, Drosophila melanogaster, for assessing the antihyperglycemic effects. RESULTS: The compounds 2a-2i demonstrated α-amylase inhibitory activity in the range of IC50 = 40.00-80.00 µg/ml as compare to standard acarbose (IC50 = 34.71 µg/ml). Compounds 2a-2i demonstrated α-glucosidase inhibitory activity in the range of IC50 = 46.01-81.65 µg/ml as compared to standard acarbose (IC50 = 34.72 µg/ml). Docking studies on a target protein, N-terminal subunit of human Maltase-glucoamylase (PDB:2QMJ) was carried and the compounds were found to dock into the active site of the enzyme (Fig. 1). The predicted binding energies of the compounds were calculated. The in vitro studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. Whereas in vivo study indicates that 2b, 2g, and 2i could lower glucose levels in the Drosophila, but then 17-30% reduced capacity than acarbose and may be overcome by adjusting their dosage. CONCLUSIONS: The in vitro and in vivo studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. This study has recognized that compounds like 2b, 2g, and 2i may be considered potential candidates for further developing a novel class of antidiabetic agents.

Radioprotective role of uric acid: evidence from studies in Drosophila and human dermal fibroblast cells.

Exposure to ionizing radiation (IR) is a common phenomenon during medical diagnosis and treatment. IRs are deleterious because cellular exposure to IR can cause a series of molecular events that may lead to oxidative stress and macromolecular damage. Radiation protection is therefore essential and significant for improving safety during these procedures. Over decades several antioxidant molecules have been screened to explore their potential as radio-protectors with little success. Therefore, the current study was carried out to confirm the role of uric acid (UA)-a putative antioxidant molecule in radioprotection using radio-resistant insect Drosophila and human dermal fibroblast (HDF) cells. Here, we demonstrate the depleted levels of UA in the mutant flies of Drosophila melanogaster-rosy and by targeting xanthine oxidase (XO an enzyme involved in UA metabolism), through maintaining flies on an allopurinol mixed diet. Allopurinol is a drug that reduces UA levels by inhibiting XO; it reduces the survival percentage in D. melanogaster compared to wild type flies following gamma irradiation at a dose of 1000 Gy. Enzymatic antioxidants such as superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx) and levels of non-enzymatic antioxidants were measured to evaluate the importance of UA. The results indicate that lack of UA reduces the total antioxidant capacity. The activity of SOD was lowered in male flies. Furthermore, we show that supplementation of UA to HDFs cells in media improved their survival rate following gamma irradiation (2 Gy). From the present study we conclude that UA is a potent antioxidant molecule present in high levels among insects. Also, it appears that UA contributes to the radiation resistance of Drosophila flies. Hence, UA emerges as a promising molecule for mitigating radiation-induced oxidative damage in higher organisms.

Levels and fluxes in enzymatic antioxidants following gamma irradiation are inadequate to confer radiation resistance in Drosophila melanogaster.

Ionizing radiation (IR) causes biological effects either by directly damaging the molecules or by generating free radicals. Antioxidant mechanisms are believed to be involved in neutralising free radicals. Levels of antioxidants therefore assume significance in determining the extent of radiation damage. The fruit fly Drosophila melanogaster (D. melanogaster) exhibits remarkable IR tolerance compared to mammals. Present study addresses the questions (1) Whether levels of antioxidants are high in radio-tolerant fruit fly D. melanogaster compared to mammals? (2) Does the antioxidant activity enhance adequately enough post-irradiation? We analysed enzymatic antioxidant profiles and their fluxes prior to and 60 min post-irradiation (50 Gy). Enzymatic antioxidants were analysed in all the developmental stages of D. melanogaster as the fruit fly shows dramatic changes in radiation resistance during development. Activity of superoxide dismutase (SOD) in Drosophila (pre-irradiation) was comparable to that of mammals. Catalase activity was lower than mammals while glutathione peroxidise (DmGPx) activity was significantly higher. Following irradiation SOD showed changes ranging from 1.40 to 1.62 folds only in larval stages. Catalase activity showed positive change of 1.25 folds only in adults. Activity of DmGPx was largely unaffected. Early pupae showed increased (3.67 fold) glutathione S-transferase activity post-irradiation. Non-enzymatic antioxidants such as total antioxidant capacity showed significant whereas reduced glutathione showed insignificant flux. In conclusion, the levels of enzymatic antioxidants in Drosophila compared to IR sensitive mammals and post-irradiation fluxes in antioxidant enzyme levels appear inadequate to explicate the dramatic radiation resistance observed in Drosophila. The observations are in agreement with the recent findings refuting the role of enzymatic antioxidants in radiation resistance.

ON and OFF pathways in Drosophila motion vision.

Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5. Here we examine how these pathways contribute to visual motion detection by combining genetic block and reconstitution of neural activity in different lamina cell types with whole-cell recordings from downstream motion-sensitive neurons. We find reduced responses to moving gratings if L1 or L2 is blocked; however, reconstitution of photoreceptor input to only L1 or L2 results in wild-type responses. Thus, the first experiment indicates the necessity of both pathways, whereas the second indicates sufficiency of each single pathway. This contradiction can be explained by electrical coupling between L1 and L2, allowing for activation of both pathways even when only one of them receives photoreceptor input. A fundamental difference between the L1 pathway and the L2 pathway is uncovered when blocking L1 or L2 output while presenting moving edges of positive (ON) or negative (OFF) contrast polarity: blocking L1 eliminates the response to moving ON edges, whereas blocking L2 eliminates the response to moving OFF edges. Thus, similar to the segregation of photoreceptor signals in ON and OFF bipolar cell pathways in the vertebrate retina, photoreceptor signals segregate into ON-L1 and OFF-L2 channels in the lamina of Drosophila.

Dietary agents in the prevention of radiation-induced nausea and vomiting (RINV): review addressing the scientific observations, benefits, lacunae and future direction.

PURPOSE: Radiation-induced Nausea and Vomiting (RINV) is an important side effect and conservative estimates are that 50-80% of the patients undergoing curative radiotherapy (RT) will experience some sought of retching, nausea, and/or vomiting during the course of their treatment. Conventionally, antiemetic drugs like the 5-hydroxytryptamine receptor antagonists and steroids are the mainstay of treatment. However, the use of these agents, especially steroids, can cause side effects and thereby negate the proposed benefits. The antiemetic effects of Centella asiatica (Indian pennywort), Hippophae rhamnoides (Sea buckthorn), oil of Mentha spicata (Spearmint) and the rhizomes of Zingiber officinale (ginger) have been addressed. CONCLUSIONS: Results indicate that Indian pennywort, Sea buckthorn, Spearmint oil and ginger are beneficial in mitigating RINV. Also, of the four plants investigated in preclinical models of study, mint oil and ginger seem to be more useful and merit structured systematic translational studies to ascertain the benefit of these two agents.

Liposome-based Freezing Medium Improves the Outcome of Mouse Prepubertal Testicular Tissue Cryopreservation.

Cryopreservation of testicular tissue holds an important role in the field of fertility preservation, particularly for prepubertal boys diagnosed with cancer. However, prepubertal testicular tissue cryopreservation is still considered to be in the experimental stage necessitating the refinement of cryopreservation protocol. Considering the fact that loss of membrane lipids is the primary cause of freeze-thaw-induced loss of testicular cell functions, in this study, we explored the beneficial properties of exogenous supplementation of membrane lipids in the form of liposomes in enhancing the cryosurvival of prepubertal testicular tissue. The freezing medium supplemented with liposomes (prepared from soy lecithin, phosphatidylethanolamine, phosphatidylserine, and cholesterol) was used for the experiments. Prepubertal testicular tissues from Swiss albino mice were cryopreserved in a liposome-containing freezing medium (LFM) composed of 0.25 mg/mL liposomes, 5% DMSO, and 30% FCS in the DMEM/F12 medium using a slow freezing protocol. The tissues were thawed and assessed for various testicular cell functions. Freezing in LFM mitigated the loss of viability, decreased malondialdehyde level (p < 0.05), and reduced apoptosis (p < 0.05) in the testicular cells compared to the testicular tissue cryopreserved in the control freezing medium (CFM). Further, DMSO (5%) appears to be the ideal penetrating cryoprotectant for prepubertal testicular tissue cryopreservation with liposome-based freezing medium. Similar enhancement in cryosurvival of cells was observed in adult human testicular tissue frozen with LFM. These findings highlight the translational value of liposome-based freezing medium in the cryopreservation of testicular tissue of prepubertal boys undergoing chemotherapy.

Comprehensive insights into the impact of bacterial indole-3-acetic acid on sensory preferences in Drosophila melanogaster.

Several bacteria of environmental and clinical origins, including some human-associated strains secrete a cross-kingdom signaling molecule indole-3-acetic acid (IAA). IAA is a tryptophan (trp) derivative mainly known for regulating plant growth and development as a hormone. However, the nutritional sources that boost IAA secretion in bacteria and the impact of secreted IAA on non-plant eukaryotic hosts remained less explored. Here, we demonstrate significant trp-dependent IAA production in Pseudomonas juntendi NEEL19 when provided with ethanol as a carbon source in liquid cultures. IAA was further characterized to modulate the odor discrimination, motility and survivability in Drosophila melanogaster. A detailed analysis of IAA-fed fly brain proteome using high-resolution mass spectrometry showed significant (fold change, ± 2; p ≤ 0.05) alteration in the proteins governing neuromuscular features, audio-visual perception and energy metabolism as compared to IAA-unfed controls. Sex-wise variations in differentially regulated proteins were witnessed despite having similar visible changes in chemo perception and psychomotor responses in IAA-fed flies. This study not only revealed ethanol-specific enhancement in trp-dependent IAA production in P. juntendi, but also showed marked behavioral alterations in flies for which variations in an array of proteins governing odor discrimination, psychomotor responses, and energy metabolism are held responsible. Our study provided novel insights into disruptive attributes of bacterial IAA that can potentially influence the eukaryotic gut-brain axis having broad environmental and clinical implications.

Fruits and their phytochemicals in mitigating the ill effects of ionizing radiation: review on the existing scientific evidence and way forward.

Although helpful in treating cancer, exposure to ionizing radiation can sometimes cause severe side effects, negating its benefit. In addition to its use in clinics, a nontoxic radioprotective agent can also be beneficial in occupational settings where humans are occupationally exposed for prolonged periods to low doses of radiation. Scientific studies using laboratory animals have shown that the fruits Aegle marmelos, Capsicum annuum, Citrus aurantium, Citrullus lanatus, Crataegus microphylla, Eugenia jambolana, Emblica officinalis, Garcinia kola, Grewia asiatica, Hippophae rhamnoides, Malus baccata, Malpighia glabra or Malpighia emarginata, Mangifera indica, Prunus domestica, Prunus avium, Prunus armeniaca, Psoralea corylifolia, Punica granatum, Solanum lycopersicum, Terminalia chebula, Vaccinium macrocarpon, Vitis vinifera and Xylopia aethiopica, and the phytochemicals gallic acid, ellagic acid, quercetin, geraniin, corilagin, ascorbic acid, hesperetin, ursolic acid, lycopene, naringin, hesperidin, rutin, resveratrol, ß-sitosterol, apigenin, luteolin, chlorogenic acid, caffeic acid, mangiferin, diosmin, ferulic acid, and kaempferol are effective in preventing radiation-induced ill effects. Clinical studies with Emblica officinalis and Punica granatum have also shown that fruits help mitigate radiation-induced mucositis, dermatitis, and cystitis. For the first time, the current review summarizes the beneficial effects of fruits and phytochemicals in mitigating radiation-induced damage, the underlying mechanisms and the existing lacunae for future studies to be undertaken for the benefit of humans and the nutraceutical and agri-based industries.

Neuroprotective effects of dietary plants and phytochemicals against radiation-induced cognitive and behavioral deficits: a comprehensive review of evidence and prospects for future research.

Exposure to ionizing radiation (IR) is a common occurrence in clinical practice and incidents involving nuclear detonation or nuclear reactor accidents. IR triggers cellular events that result in oxidative stress and damage to macromolecules, rendering it harmful. While the central nervous system (CNS) was once believed to be resistant to radiation, emerging evidence suggests that even small doses of IR can adversely impact the brain. Exposure to an unsafe dose of radiation can cause increased permeability of the blood-brain barrier (BBB), neuronal apoptosis, reduced neurogenesis, impaired synaptic plasticity, and cognitive dysfunction. In recent years, the potential benefits of dietary agents and phytochemicals for mental health and radiation-induced damage have been widely investigated. Despite this, few studies have explored the protective effects of plants against radiation-induced brain damage. Here, we present a review collating evidence on the beneficial effects of dietary plants on radiation-induced brain damage based on behavioral studies. Notably, Amaranthus paniculatus, Grewia asiatica, Lycium barbarum, and phytochemicals such as vitamin E, corilagin, curcumin, resveratrol, and ursolic acid have demonstrated potential in mitigating radiation-induced damage to the CNS. Furthermore, preliminary studies have indicated that alpha-tocopherol and the micronutrient selenium have neuroprotective effects in cancer survivors previously treated with radiation to the brain. This review focuses exclusively on behavioral outcomes to assess the impact of ionizing radiation on the CNS and the effectiveness of dietary plants and phytochemicals as neuroprotective agents against radiation-induced neuronal damage.

Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aß42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach.

Accumulation of Aß42 peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aß42-induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications. Medhya Rasayana such as Brahmi is known for its neuroprotective properties via resolving memory-related issues, while the underlying molecular mechanism of the same remains unclear. In the present study, we aimed to understand the neuroprotective effects of the aqueous extract of Bacopa monnieri and Centella asiatica (both commonly known as Brahmi) against the Aß42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identified > 90% of differentially expressed proteins from Aß42 expressing D. melanogaster were either restored to their original expression pattern or showed no change in expression pattern upon receiving either Brahmi extract treatment. The Brahmi restored proteins were part of neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also validated by negative geotaxis behavioral analysis suggesting its protective role against behavioral deficits exerted by Aß42 toxicity. We believe that these discoveries will provide a platform for developing novel therapeutics for AD management by deciphering molecular targets of neuroprotection conferred by an aqueous extract of Bacopa monnieri or Centella asiatica.

Polyvinylpyrrolidone-Capped Copper Oxide Nanoparticles-Anchored Pramipexole Attenuates the Rotenone-Induced Phenotypes in a Drosophila Parkinson's Disease Model.

Parkinson's disease (PD) is a progressive, age-related neurodegenerative disease. The disease is characterized by the loss of dopaminergic neurons in the substantia nigra, pars compacta of the midbrain. Pramipexole (PPX) is a novel drug used for the treatment of PD. It has a high affinity for the dopamine (DA) D2 receptor subfamily and acts as a targeted mitochondrial antioxidant. It is less effective in the treatment of PD due to its short half-life, highly inconvenient dosing schedule, and long-term side effects. In recent years, PPX-loaded nanoformulations have been actively reported to overcome these limitations. In the current study, we focused on increasing the effectiveness of PPX by minimizing the dosing frequency and improving the treatment strategy for PD. Herein, we report the synthesis of biodegradable polyvinylpyrrolidone (PVP)-capped copper oxide nanoparticles (PVP-CuO NPs), followed by PPX anchoring on the surface of the PVP-CuO NPs (PPX-PVP-CuO NC), in a simple and inexpensive method. The newly formulated PPX-PVP-CuO NC complex was analyzed for its chemical and physical properties. The PPX-PVP-CuO NC was tested to protect against rotenone (RT)-induced toxicity in the Drosophila PD model. The in vivo studies using the RT-induced Drosophila PD model showed significant changes in negative geotaxis behavior and the level of DA and acetylcholinesterase. In addition, oxidative stress markers such as glutathione-S-transferase, total glutathione, thiobarbituric acid reactive species, and protein carbonyl content showed significant amelioration. The positive changes of PPX-PVP-CuO NC treatment in behavior, neurotransmitter level, and antioxidant level suggest its potential role in mitigating the PD phenotype. The formulation can be used for treatment or pharmacological intervention against PD.

High doses of clethodim-based herbicide GrassOut Max poses reproductive hazard by affecting male reproductive function and early embryogenesis in Swiss albino mice.

Clethodim is a widely used and approved class II herbicide, with little information about its impact on the reproductive system. Herein, we investigated the male reproductive toxicity of clethodim using a mouse model. GrassOut Max (26% clethodim-equivalent) or analytical grade clethodim (≥90%) were given orally to male mice for 10 d in varying doses. All parameters were assessed at 35 d post-treatment. Significant decrease in testicular weight, decreased germ cell population, elevated DNA damage in testicular cells and lower serum testosterone level was observed post clethodim based herbicide exposure. Epididymal spermatozoa were characterized with significant decrease in motility, elevated DNA damage, abnormal morphology, chromatin immaturity and, decreased acetylated-lysine of sperm proteins. In the testicular cells of clethodim-based herbicide treated mice, the expression of Erß and Gper was significantly higher. Proteomic analysis revealed lower metabolic activity, poor sperm-oocyte binding potential and defective mitochondrial electron transport in spermatozoa of clethodim-based herbicide treated mice. Further, fertilizing ability of spermatozoa was compromised and resulted in defective preimplantation embryo development. Together, our data suggest that clethodim exposure risks male reproductive function and early embryogenesis in Swiss albino mice via endocrine disrupting function.

Columnar cells necessary for motion responses of wide-field visual interneurons in Drosophila.

Wide-field motion-sensitive neurons in the lobula plate (lobula plate tangential cells, LPTCs) of the fly have been studied for decades. However, it has never been conclusively shown which cells constitute their major presynaptic elements. LPTCs are supposed to be rendered directionally selective by integrating excitatory as well as inhibitory input from many local motion detectors. Based on their stratification in the different layers of the lobula plate, the columnar cells T4 and T5 are likely candidates to provide some of this input. To study their role in motion detection, we performed whole-cell recordings from LPTCs in Drosophila with T4 and T5 cells blocked using two different genetically encoded tools. In these flies, motion responses were abolished, while flicker responses largely remained. We thus demonstrate that T4 and T5 cells indeed represent those columnar cells that provide directionally selective motion information to LPTCs. Contrary to previous assumptions, flicker responses seem to be largely mediated by a third, independent pathway. This work thus represents a further step towards elucidating the complete motion detection circuitry of the fly.

Aqueous Extract of Emblica officinalis Linn (Indian gooseberry) in Combination with Iodine is More Efficacious than Iodine Alone in Mitigating Mucositis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: Retrospective Observations.

Mucositis is a very painful unavoidable and common side effect in head and neck cancer patients undergoing curative radiotherapy and can affect the planned treatment. In this study, attempt is made at understanding the efficacy of Emblica officinalis Linn (amla) when combined with providone iodine in mitigating radiation-induced mucositis, weight loss and tumor control. This was a retrospective chart based study and was carried out by extracting the data from the files of patients with cancer of head and neck who used amla in combination with iodine or iodine alone during the course of the curative radiotherapy (> 60 Gy). The data was entered in to Microsoft excel and subjected to statistical analysis using SPSS 17 software. The results indicate that when compared with iodine alone, the group where iodine and amla gargling were used was very effective in delaying mucositis, reduced incidence of intolerable mucositis (P = 0.027), quantitative grade of weight loss (P = 0.016), incidence of severe weight loss (P = 0.03) without affecting tumor response. The results suggest that when compared with iodine alone, amla when combined with iodine was more effective in mitigating radiation mucositis and by not interfering with the tumor cell kill. As far as the authors are aware of this is the first study that shows the usefulness of combining iodine with Amla in mitigating radiation-induced mucositis.

Study of Serum Zinc and Copper Levels and Tumor Pathology: A Pilot Study in People Affected with Head and Neck Cancers.

This study aimed to determine understanding the role of serum copper, zinc and copper/zinc ratio with tumor staging in people newly diagnosed to be affected with Head and Neck cancer and by comparing with age matched health individuals devoid of any orodental maladies. The study included patients confirmed to be affected with HN cancer with histological diagnosis of Head and Neck cancer (60) and age matched healthy volunteers (N = 23). The demographic details like age, domicile, menopausal status and pathological details (like tumor stage, number of lymph node involvement, tumor size) were collected from the patient's hospital data file. The serum levels of zinc and copper assayed as per standard procedures and the zinc/copper was calculated for the cancer patients and controls. The data were subjected to unpaired "t" test and ANOVA with Bonferroni's multiple comparisons. The association between zinc and copper levels with pathological details between the variables was ascertained using the Pearson correlation coefficient(r). A statistical value of p < 0.05 was considered to be significant in agreeance to the accepted norms. Results: This result of the study indicates that when compared to the healthy individuals, the serum levels of copper, and zinc, and copper/zinc ratio were high in patients with H&N cancer. Also when compared with controls, the levels of zinc decreased, while that of copper and copper/zinc ratio increased in people affected with H&N cancer (p = 0.017 to 0.0001) and with the stage of the tumor (p = 0.03 to 0.001). The results of the study suggest that levels of serum zinc were significantly lower and that of copper higher in H&N cancer patients than that in controls and also that it was dependent on the tumor stage. When analyzed cumulatively the results hint that zinc and copper, due to their role in free radical generation and prevention have an important role in cancer progression and possible prevention by judicious intervention.