Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic ...threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence potential. Thus, both thymoquinone and curcumin appeared to be promising anthelmintic compounds for further investigations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adsorption of basic fuchsin (BF) and crystal violet (CV) dyes onto iron-manganese oxide coated kaolinite (IMK) was investigated. The adsorbent was characterized using FT-IR, XRD spectra, EDX and SEM ...images. The effect of various parameters such as initial dye concentration, contact time, adsorbent dose and initial solution pH was examined. The data were fitted into non-linear two-parameter Langmuir, Freundlich, Dubinin–Radushkevich (D–R) and three-parameter Toth isotherm models. The data best fitted the Langmuir and Toth models. Langmuir saturation adsorption capacity (Qo) at 308K for BF and CV was found to be 10.36mg/g and 20.64mg/g, respectively. The value of apparent energy of adsorption obtained from non-linear D–R model (1.10–2.38kJ/mol) suggested physical adsorption of the dyes. The adsorption process followed pseudo-second order kinetics. The negative value of free energy change (2.27–6.125kJ/mol) and positive value of enthalpy change (6.70–6.68kJ/mol) indicated the feasibility, spontaneity and endothermic nature of the adsorption process. The positive value of entropy change (0.028kJ/molK) revealed increased randomness at the adsorbent–adsorbate interface. The results showed that iron-manganese oxide coated kaolinite is a promising low cost adsorbent for the removal of BF and CV dyes from wastewater.
•Iron-manganese oxide-coated kaolinite removes cationic dyes from aqueous solution.•The data best fits the Langmuir and Toth isotherm models for both dyes.•Basic fuchsin and crystal violet adsorption data obeys pseudo-second order kinetics.•Modified kaolinite proved to be a promising adsorbent for basic dye uptake.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Bardet–Biedl syndrome (BBS) is an autosomal recessive multisystemic human genetic disorder characterized by six major defects including obesity, mental retardation, renal anomalies, polydactyly, ...retinal degeneration and hypogenitalism. In several cases of BBS, few other features such as metabolic defects, cardiovascular anomalies, speech deficits, hearing loss, hypertension, hepatic defects and high incidence of diabetes mellitus have been reported as well. The BBS displays extensive genetic heterogeneity. To date, 19 genes have been mapped on different chromosomes causing BBS phenotypes having varied mutational load of each BBS gene. In this review, we have discussed clinical spectrum and genetics of BBS. This report presents a concise overview of the current knowledge on clinical data and its molecular genetics progress upto date.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host‐specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit ...geographical variation, with much higher incidence in parts of the Eastern world compared to the West. These differences are likely to reflect differences in geographical risk factors as well as genetic determinants. Of note, over the past few decades, the incidence rates of CCA appear to change and subtypes of CCA appear to show distinct epidemiological trends. These trends need to be interpreted with caution given the issues of diagnosis, recording and coding of subtypes of CCA. Epidemiological evidences suggest that in general population some risk factors are less frequent but associated with a higher CCA risk, while others are more common but associated with a lower risk. Moreover, while some risk factors are shared by intrahepatic and both extrahepatic forms, others seem more specific for one of the two forms. Currently some pathological conditions have been clearly associated with CCA development, and other conditions are emerging; however, while their impact in increasing CCA risk as single etiological factors has been provided in many studies, less is known when two or more risk factors co‐occur in the same patient. Moreover, despite the advancements in the knowledge of CCA aetiology, in Western countries about 50% of cases are still diagnosed without any identifiable risk factor. It is therefore conceivable that other still undefined etiologic factors are responsible for the recent increase of CCA (especially iCCA) incidence worldwide.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abiotic stresses (such as metals/metalloids, salinity, ozone, UV-B radiation, extreme temperatures, and drought) are among the most challenging threats to agricultural system and economic yield of ...crop plants. These stresses (in isolation and/or combination) induce numerous adverse effects in plants, impair biochemical/physiological and molecular processes, and eventually cause severe reductions in plant growth, development and overall productivity. Phytohormones have been recognized as a strong tool for sustainably alleviating adverse effects of abiotic stresses in crop plants. In particular, the significance of salicylic acid (SA) has been increasingly recognized in improved plant abiotic stress-tolerance via SA-mediated control of major plant-metabolic processes. However, the basic biochemical/physiological and molecular mechanisms that potentially underpin SA-induced plant-tolerance to major abiotic stresses remain least discussed. Based on recent reports, this paper: (a) overviews historical background and biosynthesis of SA under both optimal and stressful environments in plants; (b) critically appraises the role of SA in plants exposed to major abiotic stresses;
Water pollution due to organic contaminants is a serious issue because of acute toxicities and carcinogenic nature of the pollutants. Among various water treatment methods, adsorption is supposed as ...the best one due to its inexpensiveness, universal nature and ease of operation. Many waste materials used include fruit wastes, coconut shell, scrap tyres, bark and other tannin-rich materials, sawdust and other wood type materials, rice husk, petroleum wastes, fertilizer wastes, fly ash, sugar industry wastes blast furnace slag, chitosan and seafood processing wastes, seaweed and algae, peat moss, clays, red mud, zeolites, sediment and soil, ore minerals etc. These adsorbents have been found to remove various organic pollutants ranging from 80 to 99.9%. The present article describes the conversion of waste products into effective adsorbents and their application for water treatment. The possible mechanism of adsorption on these adsorbents has also been included in this article. Besides, attempts have been made to discuss the future perspectives of low cost adsorbents in water treatment.
► The manuscript describes the removal of pollutants by inexpensive & eco-friendly adsorbents. ► The manuscript also explicates the conversion of wastes into effective adsorbents. ► The article discusses the application of low cost adsorbents in water treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Systemic therapy for metastatic clear cell renal cell carcinoma (mccRCC) has greatly evolved over the last 15yr. More recently, combination strategies involving contemporary immunotherapy have ...emerged as key opportunities to further shift the treatment landscape.
To review the evidence regarding the efficacy and safety of standard therapeutic options in mccRCC as well as combination immunotherapy options on the horizon.
PubMed/Medline, Embase, Web of Knowledge, and Cochrane Library databases were searched up to February 2018 and according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A narrative review of studies was performed.
Twenty-six studies were included regarding therapies for metastatic RCC including vascular endothelial growth factor (VEGF)-directed therapy (n=9), mTOR inhibitors (n=2), cytokines (n=3), vaccines (n=3), and immune checkpoint inhibitors (ICIs, n=9). VEGF tyrosine kinase inhibitor monotherapy had been the standard therapy, and its use is evolving in the front-line setting with ICIs; cabozantinib provides superior progression-free survival versus sunitinib in intermediate- and poor-risk patients, by International Metastatic RCC Database Consortium criteria. The mTOR therapy is largely inferior to VEGF-directed therapy, although it has a role in combination strategies. Cytokines have largely been replaced in current practice throughout most regions, and vaccines have failed to show improved survival in phase III studies to date. ICIs have now become standard care in untreated patients with intermediate and poor risks, given overall survival benefit seen with CheckMate-214 study; survival data from IMmotion 151 are not yet mature. Several ongoing phase III combination trials, with promising early-phase data, are due to be read out.
The treatment landscape for mccRCC has evolved since the introduction of VEGF inhibitors. Combination therapies involving checkpoint inhibitors could be the next standard of care.
With the expanding role of immune checkpoint inhibitors in metastatic renal cell carcinoma, the treatment paradigm has shifted to include combination therapy in the untreated setting. As the field advances, the bar has been raised in evaluating ongoing combination strategies.
With the expanding role of immune checkpoint inhibitors in metastatic renal cell carcinoma, the treatment paradigm has shifted to include combination therapy in the untreated setting. As the field advances, the bar has been raised in evaluating ongoing combination strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The influence of salicylic acid (SA) in alleviation of salt stress in mungbean (Vigna radiata L.) through modulation of glycinebetaine (GB) and ethylene was studied. SA application at 0.5 mM ...increased methionine (Met) and GB accumulation in plants concomitant with the suppression of ethylene formation by inhibiting 1-aminocyclopropane carboxylic acid synthase (ACS) activity more conspicuously under salt stress than no stress. The increased GB accumulation together with reduced ethylene under salt stress by SA application was associated with increased glutathione (GSH) content and lower oxidative stress. These positive effects on plant metabolism induced by SA application led to improved photosynthesis and growth under salt stress. These results suggest that SA induces GB accumulation through increased Met and suppresses ethylene formation under salt stress and enhances antioxidant system resulting in alleviation of adverse effects of salt stress on photosynthesis and growth. These effects of SA were substantiated by the findings that application of SA-analogue, 2, 6, dichloro-isonicotinic acid (INA) and ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG) resulted in similar effects on Met, GB, ethylene production, photosynthesis and growth under salt stress. Future studies on the interaction between SA, GB and ethylene could be exploited for adaptive responses of plants under salt stress.
•Salicylic acid modulates glycinebetaine and ethylene production.•Salicylic acid regulates ethylene synthesis to increase salt tolerance.•Salicylic acid increases plants' sensitivity to ethylene.•Salicylic acid improves photosynthesis and growth under salt stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
With the advent of next-generation sequencing, we have an unprecedented ability to study tumor and host genomes as well as those of the vast array of microorganisms that exist within living ...organisms. Evidence now suggests that these microbes may confer susceptibility to certain cancers and may also influence response to therapeutics. A prime example of this is seen with immunotherapy, for which gut microbes have been implicated in influencing therapeutic responses in preclinical models and patient cohorts. However, these microbes may influence responses to other forms of therapy as well and may also affect treatment-associated toxicity. Based on these influences, there is growing interest in targeting these microbes in the treatment of cancer and other diseases. Yet complexities exist, and a deeper understanding of host-microbiome interactions is critical to realization of the full potential of such approaches. These concepts and the means through which such findings may be translated into the clinic will be discussed herein.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cancer and the associated secondary bacterial infections are leading cause of mortality, due to the paucity of effective drugs. Here, we have synthesized silver nanoparticles (AgNPs) from organic ...resource and confirmed their anti-cancer and anti-microbial potentials. Microwave irradiation method was employed to synthesize AgNPs using
leaf extract. Anti-cancer potential of AgNPs was evaluated by scratch assay on the monolayer of rat basophilic leukemia (RBL) cells, indicating that the synthesized AgNPs inhibit the migration of RBL cells. The synthesized AgNPs showed MIC value of 4-16 μg/mL against both Gram +ve and Gram -ve bacterial strains, exhibiting the anti-microbial potential. Biofilm inhibition was recorded at sub-MIC values against Gram +ve and Gram -ve bacterial strains. Violacein and alginate productions were reduced by 89.6 and 75.6%, respectively at 4 and 8 μg/mL of AgNPs, suggesting anti-quorum sensing activity. Exopolysaccharide production was decreased by 61-79 and 84% for Gram -ve and Gram +ve pathogens respectively. Flagellar driven swarming mobility was also reduced significantly. Furthermore,
study confirmed their tolerability in mice, indicating their clinical perspective. Collective, we claim that the synthesized AgNPs have anti-metastasis as well as anti-microbial activities. Hence, this can be further tested for therapeutic options to treat cancer and secondary bacterial infections.
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