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PDF file - 94KB, Effect of RES on body weight and food consumption in PTEN knockout mice

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PDF file - 60KB, Apoptosis in SIRT1 knockdown DU145 cells

PDF file - 79KB, Effect of RES on the protein levels of p4E-BP1 and FOXO-3 in prostate cancer cells

This file contains detailed methods for publication as supplementary information.

(S1) List of primer pairs used in qPCR, (S2) list of upregulated genes following NQO1 KD, (S3) list of down-regulated genes following NQO1 KD.

(S1) Basal NQO1 levels in different cancer cells, (S2) Transduction efficiency of NQO1 KD, (S3 and S4) Effects of KD on cellular redox state and AR signaling, (S5) heat maps of differential gene expression with NQO1 KD, (S6) inhibition of NQO1 activity on NFkB-p65 signaling, (S7) Quantification of increased nuclear IKKa following NQO1 KD and (S8) Basal IL-8 message in prostate cancer cells.

NADPH reductase NAD(P)H:quinone oxidoreductase 1 (NQO1) is needed to maintain a cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on the basis of studies in NQO1-deficient mice. In this work, we sought deeper insights into how NQO1 contributes to prostate carcinogenesis, a setting in which oxidative stress and inflammation are established contributors to disease development and progression. In the TRAMP mouse model of prostate cancer, NQO1 was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells increased levels of nuclear IKKα and NF-κB while decreasing the levels of p53, leading to interactions between NF-κB and p300 that reinforce survival signaling. Gene expression analysis revealed upregulation of a set of immune-associated transcripts associated with inflammation and tumorigenesis in cells in which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased migration, including under conditions of androgen deprivation. These results reveal a molecular link between NQO1 expression and proinflammatory cytokine signaling in prostate cancer. Furthermore, our results suggest that altering redox homeostasis through NQO1 inhibition might promote androgen-independent cell survival via opposing effects on NF-κB and p53 function. Cancer Res; 74(19); 5644–55. ©2014 AACR.

This research investigates the heavy metals (Zn, Cd, Cu and Pb) concentration in water, sediments and macrophytes in Ghodaghodi Lake during winter and summer seasons of 2019 to find out the bioaccumulation of metals and phytoremediation potential of locally available macrophytes. Atomic absorption spectrophotometer with acid digestion method was used for analysis of heavy metals. The mean heavy metals concentration during summer and winter season were in the order: Zn > Cu > Pb > Cd in water and sediments. The mean concentrations of Cd, Cu and Pb were significantly higher in winter (0.79±0.71, 12.99±3.16, and 11.39±6.88 mg/g, respectively) than summer season (0.01±0.00, 9.13±5.21, and 2.16±6.64 mg/g, respectively) in sediments which is also supported by geo-accumulation index. Zinc had also higher concentrations in winter (65.29±13.13 mg/g) compared to summer (44.00±21.08 mg/g), though not significant. Ludwigia sp. was more capable of accumulating heavy metals than the Nymphaea sp. in winter season. On the other hand, Nelumbo sp. was more effective of accumulating heavy metals (except Zn) compared to Ludwigia sp. in summer season. The highest bioaccumulation factor (macrophyte/sediment) for Ludwigia sp. (common in both seasons) was observed for Cd in winter and Pb in summer season. Thus, although there were some variations in potentiality of bioaccumulation among the species, these macrophytes are capable of accumulating heavy metals providing scope in bioremediation field.

With the development of immune checkpoint blockade to treat a variety of malignancies, better predictive biomarkers as well as new targets to further improve anti-tumor immunity remains a need. Our understanding of the role of angiogenesis in immune regulation continues to improve, and combinations of anti-angiogenesis and immune checkpoint blockade demonstrate improved clinical efficacy, as well as mechanisms for improved immune cell trafficking. Tumor biopsies from a phase I study with 46 advanced melanoma patients treated with Ipilimumab and Bevacizumab combination (Ipi-Bev) therapy, revealed activated endothelium accompanied by lymphocyte infiltration. To discover possible targets involved in the observed clinical benefit, a serological screen was performed using human protein arrays with post-treatment plasma samples of long-term patients with clinical benefit to Ipi-Bev therapy (Wu et. al., 2017; Hodi et. al., 2014). EDIL3 (EGF Like Repeats and Discoidin Domains 3), a pro-angiogenic extracellular matrix protein, was identified. Humoral responses against EDIL3 were associated with favorable clinical outcomes including improved response rates (p=0.003) and overall survival (p=0.03) to Ipi-Bev therapy. The anti-EDIL3 response was also observed to be significantly (p=0.03) related to Ipi-Bev treatment when compared with patients treated with Ipilimumab alone, anti-PD1 therapy alone, or the combination of Ipilimumab and Nivolumab in a combined analysis. Transcriptome analyses of TCGA SKCM (n=469) and BMS Checkmate 064 trial (n=90) related upregulated EDIL3 expression with enrichment of EMT, TGFβ signaling in fibroblasts, and angiogenesis signatures. Interestingly, TIDE analysis demonstrated a role for EDIL3 in T cell exclusion and immunosuppressive cancer-associated fibroblasts (CAFs) as its source in the tumor microenvironment. EDIL3 was also predicted as a biomarker of non-response to immune checkpoint blockade treatment. In vitro studies confirmed the upregulation of EDIL3 expression and secretion by patient-derived CAFs along with its role in modulating TGFβ1 mediated EMT. Mechanistically, EDIL3 was found to interfere with leukocyte-endothelial interactions by disturbing LFA-1/ICAM1 mediated adhesion and inhibited T cell transmigration in 2-D and microfluidic 3-D coculture studies with patient-derived tumor endothelial cells. Our findings suggest that the humoral response against EDIL3 may serve as one of the underlying mechanisms involved in effectuating an excluded to an inflamed phenotype observed in responders of checkpoint blockade treatment. This study develops EDIL3 as a potential target to enhance cytotoxic immune responses and improve the outcomes of combination immune therapy. Studies are ongoing for targeted inhibition of EDIL3 with implications for therapeutic application to promote anti-tumor immunity. Citation Format: Saba Tabasum, Dinesh Thapa, Anita Giobbie-Hurder, Jason L. Weirather, Xinqi Wu, Marco Campisi, Xiaoyun Li, Jingjing Li, Michael P. Manos, David A. Barbie, F. Stephen Hodi. An angiogenic target of immune exclusion with checkpoint blockade in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5864.

The contribution of the gut microbiota to health and disease is becoming ever more apparent in the last number of years, due to developments in DNA sequencing technology and more well-defined cultivation techniques. This has resulted in the identification of health-promoting bacteria. Until recently, prebiotics, non-digestible food substrates which are selectively utilised by beneficial bacteria, were employed with a view to increasing the growth of well-established health promoting bacteria, namely Lactobacillus and Bifidobacterium. However, other beneficial bacteria recently revealed may also be targeted to enhance their growth as they establish themselves as the next generation of health-promoting microbes. These include anaerobes such as Akkermansia muciniphila, Faecalibacterium prausnitziiand Eubacterium rectale. Identification of growth substrates/bioactives through the analysis of genome sequence data can aid in elucidating which substrates may best enhance the growth of these microbes which are often difficult to grow. The phenotypic microbial trait analyser, Traitar, can predict 67 phenotypes based on the genome sequence inputted. Some of these traits include substrates that could potentially be utilised by the bacteria. Another tool, CarveMe, which has been created with the aim of making metabolic modelling more user-friendly, was also used with the same genomes. A select number of substrates identified in both tools have been chosen to be evaluated in vitroin order to establish the accuracy of these predictive tools as well as giving an indication as to how these beneficial microbes can be modulated through dietary components.

Electrides, which are ionic crystals composed of excess anionic electrons, are of great interest as an exotic material for fundamental research and practical applications in broad fields of science and technology. However, an inherent chemical instability under ambient conditions at room temperature has been a fatal drawback to be addressed. Here, we report that transition metal-rich monochalcogenides are an emerging class of low-dimensional electrides with excellent chemical and thermal stability in air and water at room temperature through a comprehensive exploration of theoretical prediction and experimental verification. We predict new two-dimensional (2D) electrides crystallized in hexagonal

Background: Spinal injury is the most common injury which may lead to devastating disability. Such fractures are relatively rare but frequently result in neurologic damage due in part to retro- pulsed fragments that narrow the spinal canal. Hereby we would like to correlate the CT scan findings and neurologic impairment in thoracolumbar burst fractures at our center. Materials and Methods: This prospective observational study was conducted at B&C teaching hospital, Birtamode, Nepal. Patients were evaluated by CT scan between July 2016 to December 2018 referred from the emergency department with a history of trauma and suspected thoracolumbar vertebral fractures with or without neurological deficit were included in the study. The different demographic variables like gender, age were included and injury at the level of the spine and neurological deficit was studied. Thus, obtained data were processed in statistical software and expressed in percentage and frequency. Results: The total number of patients was 34 (male: 19, female: 15). The age ranged from 16 years to 77 years with a mean age of 39.1 years. The neurologic deficit was detected in 10 cases (29.4%), out of which complete deficit in 6 (60%) and incomplete deficit in 4 (40%). The neurologic deficit was absent in 24 cases (70.6%). An associated laminar fracture was detected in 17 patients (50%). Laminar fracture associated with the neurologic deficit was found in 10 patients. Conclusion: CT scan is an excellent imaging modality for the evaluation of thoracolumbar fractures. Measurement of central canal ratio and assessment of associated laminar fracture can be useful information to predict the neurologic deficit and plan for further management.

The human intestinal commensal microbiota and associated metabolic products have long been regarded as contributors to host health. As the identity and activities of the various members of this community have become clearer, newly identified health-associated bacteria, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Ruminococcus bromii and Roseburia species, have emerged. Notably, the abundance of many of these bacteria is inversely correlated to several disease states. While technological and regulatory hurdles may limit the use of strains from these taxa as probiotics, it should be possible to utilize prebiotics and other dietary components to selectively enhance their growth in situ. Dietary components of potential relevance include well-established prebiotics, such as galacto-oligosaccharides, fructo-oligosaccharides and inulin, while other putative prebiotics, such as other oligosaccharides, polyphenols, resistant starch, algae and seaweed as well as host gut metabolites such as lactate and acetate, may also be applied with the aim of selectively and/or differentially affecting the beneficial bacterial community within the gastrointestinal environment. The present review provides an overview of the dietary components that could be applied in this manner.

Copper (Cu) nanoparticles (NPs) have received extensive interest owing to their advantageous properties compared with their bulk counterparts. Although the natural oxidation of Cu NPs can be alleviated by passivating the surfaces with additional moieties, obtaining non-oxidized bare Cu NPs in air remains challenging. Here we report that bare Cu NPs with surface excess electrons retain their non-oxidized state over several months in ambient air. Cu NPs grown on an electride support with excellent electron transfer ability are encapsulated by the surface-accumulated excess electrons, exhibiting an ultralow work function of ~3.2 eV. Atomic-scale structural and chemical analyses confirm the absence of Cu oxide moiety at the outermost surface of air-exposed bare Cu NPs. Theoretical energetics clarify that the surface-accumulated excess electrons suppress the oxygen adsorption and consequently prohibit the infiltration of oxygen into the Cu lattice, provoking the endothermic reaction for oxidation process. Our results will further stimulate the practical use of metal NPs in versatile applications.

Purely quantum electron systems exhibit intriguing correlated electronic phases by virtue of quantum fluctuations in addition to electron-electron interactions. To realize such quantum electron systems, a key ingredient is dense electrons decoupled from other degrees of freedom. Here, we report the discovery of a pure quantum electron liquid, which spreads up to ~ 3 {\AA} in the vacuum on the surface of electride crystal. An extremely high electron density and its weak hybridisation with buried atomic orbitals evidence the quantum and pure nature of electrons, that exhibit a polarized liquid phase as demonstrated by our spin-dependent measurement. Further, upon enhancing the electron correlation strength, the dynamics of quantum electrons changes to that of non-Fermi liquid along with an anomalous band deformation, suggestive of a transition to a hexatic liquid crystal phase. Our findings cultivate the frontier of quantum electron systems, and serve as a platform for exploring correlated electronic phases in a pure fashion., Comment: 29 pages, 4 figures, 10 extended data figures

Essential oils (EO) are widely used in foods as flavoring and preservative agents. Many of the biological activities of EO have been attributed to major essential oil compounds (EOC) but their direct interaction with colonic epithelial cells and their genotoxic and genoprotective effects are not well established. In this study, the cytotoxicity and genotoxicity of EOC including nerolidol, thymol, geraniol, methylisoeugenol, eugenol, linalool, and a commercial blend (Agolin) were determined. Furthermore, the genoprotective effects of EOC against oxidative and methylating damage were assessed using the comet assay in HT-29 colorectal adenocarcinoma cells. The majority of EOC were cytotoxic to HT-29 cells at or above 250 ppm after 24 hr exposure. At noncytotoxic doses, none of the EOC was genotoxic in the comet assay. Genoprotection against oxidative DNA damage was observed for nerolidol (at 62.5 ppm), thymol (at 12.5 ppm), geraniol, and methylisoeugenol (both at 125 ppm), as well as linalool and Agolin (both at 250 ppm). Thymol was the most protective compound against oxidative DNA damage and geraniol (at 125 ppm) also protected cells against methylating DNA damage. This study highlights the potential of EOC such as thymol to protect the colonic epithelium against oxidative DNA damage and geraniol against methylating DNA damage. Further in vivo studies are needed to confirm these findings for safety and efficacy to exploit their potential pharmaceutical or nutraceutical uses for colonic health.

The hilly regions of Nepal are potential for land sliding in rainy season. Lying between two major thrusts: Main Frontal Thrust (MFT) and Main Boundary Thrust (MBT), the rocks of Siwalik zone are very weak and fragile. Shallow and deep landslides are very common in the Siwalik zone during heavy and continuous rainfall. The landslide in the busy road and agglomerate settlements are destroying the life and properties every year in rainy season. This study aims to develop a landslide susceptibility map of Chatara-Barahakshetra area, Siwalik zones of eastern Nepal by the means of frequency ratio model. The paper utilized the remote sensing and GIS to develop a landslide susceptibility map. Total of 382 landslide polygons were mapped from Google earth and by field verification. The validation results showed that the success rate curve with 72.55 percentage of the area lying under the curve and the prediction rate curve with 71.73 percentage of the area lying under the curve indicating that prediction ability of the Frequency Ratio model. These landslide susceptibility maps can be used as a planning tool by prioritizing areas for controlling the landslide effects. More than 71% success rate indicate that frequency ratio model is suitable model for the landslide susceptibility in the study area.

Magnetism of pure electrons is fundamental for understanding diverse magnetic phenomena in condensed matters but has not been fully investigated in experiments due to the lack of a tractable model system. Such an exotic material necessitates an exclusive magnetic interaction of electrons being devoid of orbital and lattice degrees of freedom. Here, we report the two-dimensional mixed-cation [YGdC]2+∙2e− electride, showing ferrimagnetic nature from the direct exchange interaction of magnetic interstitial electrons in interlayer space. We identify that magnetic interstitial electrons are periodically localized in octahedral and tetrahedral cavities between 2D cationic Y2−xGdx arrays. The mixed configuration of non-magnetic and magnetic cations in cavities induces divergent spin states and interactions of magnetic interstitial electrons, in which their direct exchange interaction overwhelms the interactions with magnetic cations, triggering the ferrimagnetic spin-alignment. This discovery facilitates further exploration of magnetic electrides and nurtures the study of two-dimensional magnetism of layered crystals and electron phases.

The NAD+-dependent deacetylase, Sirtuin 1 (SIRT1) is involved in prostate cancer pathogenesis. However, the actual contribution is unclear as some reports propose a protective role while others suggest it is harmful. We provide evidence for a contextual role for SIRT1 in prostate cancer. Our data show that (i) mice orthotopically implanted with SIRT1-silenced LNCaP cells produced smaller tumors; (ii) SIRT1 suppression mimicked AR inhibitory effects in hormone responsive LNCaP cells; and (iii) caused significant reduction in gene signatures associated with E2F and MYC targets in AR-null PC-3 and E2F and mTORC1 signaling in castrate-resistant ARv7 positive 22Rv1 cells. Our findings further show increased nuclear SIRT1 (nSIRT1) protein under androgen-depleted relative to androgen-replete conditions in prostate cancer cell lines. Silencing SIRT1 resulted in decreased recruitment of AR to PSA enhancer selectively under androgen-deprivation conditions. Prostate cancer outcome data show that patients with higher levels of nSIRT1 progress to advanced disease relative to patients with low nSIRT1 levels. Collectively, we demonstrate that lowering SIRT1 levels potentially provides new avenues to effectively prevent prostate cancer recurrence.

In semiconductor physics, the Urbach rule describes an exponential dependence of the UV-Vis absorption coefficient on photon energy at the band edge. The rule is so ubiquitously applied that a single common mechanism, variability in the local potential, is generally considered to be the cause of exponential band edges. Variability in the local potential may be caused by alloy inhomogeneity, structural defects, impurities, thermal excitation, or any other mechanism that interrupts ideal crystallinity and creates disorder. A crucial point of the Urbach rule is its development for band edges which approach linearity when plotted on a logarithmic scale. The rule was not developed in the context of nonlinear band edges with complex fine structure. Even so, this model has been applied extensively to band edges with such features. Using differential analysis and deconvolution, we develop an analytical technique capable of separating the components responsible for the fine structure observed. This approach reduces challenging signal-artifact convolution problems to a simple linear combination. Furthermore, we develop a model that can be applied to the nonlinear band-edge signals extracted. We show that in the limiting case of linearity, our model is consistent with and produces the same results as the linear Urbach model. Our model is capable of bypassing ``tailing'' as an indirect measure of the spread in the local potential and gives a direct measure of this quantity.

NAD[P]H:quinone oxidoreductase 1 (NQO1) regulates cell fate decisions in response to stress. Oxidative stress supports cancer maintenance and progression. Previously we showed that knockdown of NQO1 (NQO1low) prostate cancer cells upregulate pro-inflammatory cytokines and survival under hormone-deprived conditions. Here, we tested the ability of NQO1low cells to form tumors. We found NQO1low cells form aggressive tumors compared with NQO1high cells. Biopsy specimens and circulating tumor cells showed biochemical recurrent prostate cancer was associated with low NQO1. NQO1 silencing was sufficient to induce SMAD-mediated TGFβ signaling and mesenchymal markers. TGFβ treatment decreased NQO1 levels and induced molecular changes similar to NQO1 knockdown cells. Functionally, NQO1 depletion increased migration and sensitivity to oxidative stress. Collectively, this work reveals a possible new gatekeeper role for NQO1 in counteracting cellular plasticity in prostate cancer cells. Further, combining NQO1 with TGFβ signaling molecules may serve as a better signature to predict biochemical recurrence., Thapa et al find that depletion of the antioxidant enzyme NAD[P]H:Quinone Oxidoreductase 1 (NQO1) accelerates prostate tumorigenesis and induces the epithelial-to-mesenchymal transition by activating TGFβ signaling. They also find that low NQO1 is associated with mesenchymal signature and biochemical recurrence in clinical samples.

MgxZn1−xO thin films were grown as metastable alloys via a sputtering technique in order to achieve single-phase wurtzite alloys with deep-UV optical bandgaps. As-grown alloys with Mg composition range 0–72% resulted in optical bandgaps spanning the UV-range of 3.3–4.4 eV. The thermal stability of the alloys was studied via post-growth controlled annealing experiments up to 900 °C. Alloys with low Mg up to 34% were found to be highly stable and retained their optical and material properties; however, alloys with higher Mg, up to 72%, were found to be unstable and were phase separated into wurtzite and cubic structural phases with respective optical bandgaps at ~ 3.5 and 6.0 eV. Both the as-grown and annealed alloys were studied using X-ray diffraction for structural identification, transmission spectroscopy for bandgap analysis, and Raman scattering for mapping the phonon mode-behavior. The experimental value for the solubility limit was found to be ~ 30%. A straightforward model calculation based on the Raman-mode saturation behavior yielded a similar value for the solubility limit of the alloys. The results are discussed in terms of available phase-diagrams for stable-state ceramics alloys that were grown under thermodynamics equilibrium conditions.

Cannabinoid receptor 1 (CB1) activation has been reported to reduce transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced inflammatory responses and is anti-nociceptive and anti-inflammatory in corneal injury. We examined whether allosteric ligands, can modulate CB1 signaling to reduce pain and inflammation in corneal hyperalgesia. Corneal hyperalgesia was generated by chemical cauterization of cornea in wildtype and CB2 knockout (CB2&minus, /&minus, ) mice. The novel racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229 were examined alone or in combination with the orthosteric CB1 agonist &Delta, 8-tetrahydrocannabinol (&Delta, 8-THC). Pain responses were assessed following capsaicin (1 &micro, M) stimulation of injured corneas at 6 h post-cauterization. Corneal neutrophil infiltration was also analyzed. GAT228, but not GAT229 or GAT211, reduced pain scores in response to capsaicin stimulation. Combination treatments of 0.5% GAT229 or 1% GAT211 with subthreshold &Delta, 8-THC (0.4%) significantly reduced pain scores following capsaicin stimulation. The anti-nociceptive effects of both GAT229 and GAT228 were blocked with CB1 antagonist AM251, but remained unaffected in CB2&minus, mice. Two percent GAT228, or the combination of 0.2% &Delta, 8-THC with 0.5% GAT229 also significantly reduced corneal inflammation. CB1 allosteric ligands could offer a novel approach for treating corneal pain and inflammation.

Staphylococcus epidermidis is a commensal species that has been increasingly identified as a nosocomial agent. Despite the interest, little is known about the ability of S. epidermidis isolates to adapt to different ecological niches through comparisons at genotype or phenotype levels. One niche where S. epidermidis has been reported is the human gut. Here, we present three S. epidermidis strains isolated from feces and show that they are not phylogenetically distinct from S. epidermidis isolated from other human body sites. Both gut and skin strains harbored multiple genes associated with biofilm formation and showed similar levels of biofilm formation on abiotic surfaces. High-throughput physiological tests using the BIOLOG technology showed no major metabolic differences between isolates from stool, skin, or cheese, while an isolate from bovine mastitis showed more phenotypic variation. Gut and skin isolates showed the ability to metabolize glycine-conjugated bile acids and to grow in the presence of bile, but the gut isolates exhibited faster anaerobic growth compared to isolates of skin origin.

Discoveries of two-dimensional (2D) magnetism originated from confined atomic layers in van der Waals (vdW) crystals provide an interesting arena for elucidating its fundamentals and enrich magneto-electric and quantum properties. However, a material that exhibits intrinsic 2D magnetism of interstitial electrons occupying layered space, as a root system of magnetic vdW crystals, remains obscure. In this work, 2D ferromagnetic vdW electride, [RECl]2+·2e− (RE = Y and La) is reported with perfectly isolated ferromagnetic 2D blocks encompassing quasi-atomic electron layers. The ferromagnetism of the vdW electride with Curie temperature of 100 K originates from the spin-polarized quasi-atomic electrons with a substantial moment up to ∼0.91 Bohr magneton, which behave as magnetic elements in paramagnetic lattice framework. Invariable ferromagnetism at the monolayer limit strongly supports the 2D ferromagnetism of quasi-atomic electrons. These findings expand the variety of 2D magnetic crystals, providing a promising platform to study the emergent magnetism of low-dimensional electron phases.

Ethanopharmacological relevance The process of formation or appearance of a urinary stone anywhere in the renal tract is known as urolithiasis. It is a longstanding health problem, known to exist since early age of civilization. Records about symptoms, signs and treatment strategies of urinary stones diseases are found in the several ancient texts of traditional medicines such as Ayurveda, Traditional Chinese Medicine (TCM), Siddha and Unani. In Ayurveda, urolithiasis has been considered as one of the eight most troublesome diseases. Ayurvedic management and cure of urinary stone involves herbal formulas, alkaline liquids and surgical procedures. Whereas, TCM recommends polyherbal drugs, acupuncture and mexibustion for treatment of the urinary stones. Among these therapies, herbal remedies are in practice till today for the treatment and cure urinary stone diseases. Materials and methods A comprehensive review of the scientific literature about pathophysiology of urinary stones and antiurolithiatic plants was undertaken using the following bibliographic databases: MEDLINE/PubMed, Scopus, Web of Knowledge and Google Scholar. The search was conducted from publications from all years until Dec., 2015 by combination of the search terms and Boolean operators; ‘urinary stone’ OR ‘kidney stone’ AND ‘plant’ OR ‘medicine’ OR ‘antiurolithiatic plants’. Outputs were restricted to those completed studies only published in English. In this review, literatures about plants which are used as diuretic and/or in treatment urinary tract infections have not also been considered. The Plant List and Royal Botanical Garden, Kew databases were used to authenticate botanical names of plants. Books and monographs published in English were used to collect information about historical records of antiurolithiatic plants. Results Recent pharmacological interventions accredited ancient antiurolithiatic claims to several plants and their formulations. The majority of antiurolithiatic plants were found to either dissolve the stones or inhibit the process of urinary stone formation. Plants such as Phyllanthus niruri L. and Elymus repens (L.) Gould, as well as herbal products including ‘Wu-Ling-San’ formula, ‘Cystone’ and ‘Herbmed’ have been proved their utility as promising antiurolithiatic medicines in the different phases of clinical trials. In addition, some of the isolated phytochemicals such as berberine, lupeol, khelin, visnagin, 7-hydroxy-2′,4′,5′-trimethoxyisoflavone and 7-hydroxy-4′-methoxyisoflavone were reported to have potent antiurolithiatic activity. Conclusion In ancient medicinal texts, antiurolithiatic potential has been ascribed to several plants and their formulations. Present scientific studies provide scientific evidences for few of these claims however, they are insufficient to establish many of these plants and herbal formulations as therapeutic remedies for the treatment and management of urinary stones. Conversely, findings of pre-clinical and clinical studies about some plants and herbal formulations are promising, which underlines the utility of herbal remedies as alternative medicines for the treatment and management of urinary stones in the future.

Persistent Mullerian duct syndrome is a rare entity and usually presents with common symptoms of undescended testis and hernia. The syndrome is caused by an insufficient amount of Mullerian inhibiting substance or due to the insensitivity of the target organ to Mullerian inhibiting substance. Polysplenia is a rare congenital disease manifested by multiple small accessory spleens. The association of these two entities, Persistent Mullerian duct syndrome and polysplenia, is rare and has not been reported in the literature. We reported a case of a 27 years old male presented with complains of right flank pain and nausea. Ultrasound showed right ureteric calculus with hydronephrosis and elongated soft tissue mass posterior to bladder. Contrast enhanced Computed Tomography showed soft tissue suggestive of infantile uterine structure with multiple splenculi and short pancreas. He was diagnosed as Persistent Mullerian duct syndrome with unilateral cryptorchidism, polysplenia and short pancreas, coincidentally detected while evaluating for ureteric colic. He underwent Ureteroscopic Lithotripsy with stenting for ureteric calculus, however, he refused laparotomy with excision of mullerian structures. Keywords: cryptorchidism; persistent mullerian duct syndrome; short pancreas.

Background: In this present world, human beings are being exposed directly or indirectly to some kind of ionizing and non-ionizing radiations with the development of recent scientific technologies or by natural phenomena. The study of the measurement of power density (PD) or Radio Frequency (RF) radiated from cellular Base Station Towers (BSTs) is seemed to be important in Nepal like other countries because of its various health effects. In this study, the authors measured the PD radiated from mobile base station towers in Biratnagar sub-metropolitan city, Morang. Methods and Methodology: All together 18 BSTs were selected within Biratnagar for the study purpose. Tenmars TM-196 which is a non-ionizing radiation detector was used to measure the power density. The Global Positioning System (GPS), a space-based satellite navigation system was used to locate the Maximum Peak Point (MPP) from the BSTs. Result: The maximum power density (PD) was observed near Jogbani boarder i.e. 3781.0 µW/m2 which was 0.63% of the NTA guidelines. Similarly, the minimum power density was observed near Rani BRT i.e 1549.3 µW/m2which was 0.26% of the NTA guidelines. Conclusion: From the survey it can be concluded that there is no significant health hazard to the general people due to non-ionizing radiation radiated from Base Station Towers in Biratnagar. Int J Appl Sci Biotechnol, Vol 4(3): 338-345

ZnO is an efficient luminescent material in the UV-range ∼3.4 eV with a wide range of applications in optical technologies. Sputtering is a cost-effective and relatively straightforward growth technique for ZnO films; however, most as-grown films are observed to contain intrinsic defects which can significantly diminish the desirable UV-emission. In this research the defect dynamics and optical properties of ZnO sputtered films were studied via post-growth annealing in Ar or O2 ambient, with X-ray diffraction (XRD), imaging, transmission and Urbach analysis, Raman scattering, and photoluminescence (PL). The imaging, XRD, Raman and Urbach analyses indicate significant improvement in crystal morphology and band-edge characteristics upon annealing, which is nearly independent of the annealing environment. The native defects specific to the as-grown films, which were analyzed via PL, are assigned to Zni related centers that luminesce at 2.8 eV. Their presence is attributed to the nature of the sputtering growth technique, which supports Zn-rich growth conditions. After annealing, in either environment the 2.8 eV center diminished accompanied by morphology improvement, and the desirable UV-PL significantly increased. The O2 ambient was found to introduce nominal Oi centers while the Ar ambient was found to be the ideal environment for the enhancement of the UV-light emission: an enhancement of ∼40 times was achieved. The increase in the UV-PL is attributed to the reduction of Zni-related defects, the presence of which in ZnO provides a competing route to the UV emission. Also, the effect of the annealing was to decrease the compressive stress in the films. Finally, the dominant UV-PL at the cold temperature regime is attributed to luminescent centers not associated with the usual excitons of ZnO, but rather to structural defects.

To realize the many potential applications of ZnO films, it is vital to produce films with high optical quality that exhibit strong UV luminescence. By combining annealing at an optimal temperature followed by the deposition of a coating, one can achieve a significant enhancement of photoluminescence (PL). The effectiveness of the coating over time is a crucial point to be considered. Three types of coating materials were investigated: MgO, SiO2, and Al2O3. Due to its strong bond energy, MgO was found to be the most effective coating material for passivation of the surfaces of the ZnO films; SiO2 was the second best. The UV-PL intensity of MgO coated ZnO was found to increase by a factor of 52 relative to an uncoated film. The effectiveness of the coatings exhibited a linear correlation with their bond energies and is discussed in terms of competing mechanisms to surface passivation such as the adsorption of OH-groups; these can act as surface traps and diminish the UV-PL intensity. Annealing at 900 °C prior to the deposition of the coating was found to be an important step in realizing the optimal performance of the coating due to the reduction of Zn interstitials accompanied by improved crystallinity. Exposure to the environment, up to 294 days, results in the degradation of the UV-PL of the MgO coated film; this effect was not observed for the film coated with SiO2. This effect is discussed in terms of the strong reactivity of MgO with environmental contaminants from the OH-groups.

Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia. Methods: Corneal hyperalgesia (increased pain response) was generated using chemical cauterization of the corneal epithelium in wild-type (WT) and CB2R knockout (CB2R−/−) mice. Cauterized eyes were treated topically with the phytocannabinoids Δ8-tetrahydrocannabinol (Δ8THC) or cannabidiol (CBD), or the CBD derivative HU-308, in the presence or absence of the CB1R antagonist AM251 (2.0 mg/kg i.p.), or the 5-HT1A receptor antagonist WAY100635 (1 mg/kg i.p.). Behavioral pain responses to a topical capsaicin challenge at 6 h postinjury were quantified from video recordings. Mice were euthanized at 6 and 12 h postcorneal injury for immunohistochemical analysis to quantify corneal neutrophil infiltration. Results: Corneal cauterization resulted in hyperalgesia to capsaicin at 6 h postinjury compared to sham control eyes. Neutrophil infiltration, indicative of inflammation, was apparent at 6 and 12 h postinjury in WT mice. Application of Δ8THC, CBD, and HU-308 reduced the pain score and neutrophil infiltration in WT mice. The antinociceptive and anti-inflammatory actions of Δ8THC, but not CBD, were blocked by the CB1R antagonist AM251, but were still apparent, for both cannabinoids, in CB2R−/− mice. However, the antinociceptive and anti-inflammatory actions of HU-308 were absent in the CB2R−/− mice. The antinociceptive and anti-inflammatory effects of CBD were blocked by the 5-HT1A antagonist WAY100635. Conclusion: Topical cannabinoids reduce corneal hyperalgesia and inflammation. The antinociceptive and anti-inflammatory effects of Δ8THC are mediated primarily via CB1R, whereas that of the cannabinoids CBD and HU-308, involve activation of 5-HT1A receptors and CB2Rs, respectively. Cannabinoids could be a novel clinical therapy for corneal pain and inflammation resulting from ocular surface injury.

Chronic inflammation is postulated to influence prostate cancer progression. Preclinical studies have claimed that inflammatory mediators are involved in prostate cancer development and therefore suggested these as attractive targets for intervention. However, among the many pro-inflammatory mediators, there is no consensus regarding the identity of the primary one(s). In clinical studies, chronic inflammation has been found in prostate tumor specimens, and tissues resected for treatment of benign prostatic hyperplasia (BPH). Although collective evidence from molecular, experimental and clinical data suggests that inflammation can contribute or promote prostate carcinogenesis, an etiologic link has not yet been established. Moreover, the role of chronic inflammation in the onset of castration resistant and metastatic disease is unclear. Therefore it is important to open a dialog regarding recent findings on how chronic inflammatory mediators contribute to prostate cancer progression, and their usefulness to prevent disease progression. In this commentary, we assess the current literature with respect to chronic inflammation as a potential initiator and promoter of prostate carcinogenesis and discuss the prospects for its potential clinical applications.

A static batch culture system inoculated with human faeces was used to determine the influence of essential oil compounds (EOCs) on mixed faecal microbiota. Bacteria were quantified using quantitative PCR of 16S rRNA genes. Incubation for 24 h of diluted faeces from six individuals caused enrichment of Bifidobacterium spp., but proportions of other major groups were unaffected. Thymol and geraniol at 500 p.p.m. suppressed total bacteria, resulting in minimal fermentation. Thymol at 100 p.p.m. had no effect, nor did eugenol or nerolidol at 100 or 500 p.p.m. except for a slight suppression of Eubacterium hallii. Methyl isoeugenol at 100 or 500 p.p.m. suppressed the growth of total bacteria, accompanied by a large fall in the molar proportion of propionate formed. The relative abundance of Faecalibacterium prausnitzii was unaffected except with thymol at 500 p.p.m. The ability of EOCs to control numbers of the pathogen Clostridium difficile was investigated in a separate experiment, in which the faecal suspensions were amended by the addition of pure culture of C. difficile. Numbers of C. difficile were suppressed by thymol and methyl isoeugenol at 500 p.p.m. and to a lesser extent at 100 p.p.m. Eugenol and geraniol gave rather similar suppression of C. difficile numbers at both 100 and 500 p.p.m. Nerolidol had no significant effect. It was concluded from these and previous pure-culture experiments that thymol and geraniol at around 100 p.p.m. could be effective in suppressing pathogens in the small intestine, with no concern for beneficial commensal colonic bacteria in the distal gut.