64 research outputs found
Representation of Minorities in Research: A View from the Community
No full textAUTHOR AFFILIATION: Sudarshan Pyakurel, Arogya Institute and Bhutanese Nepali Community of Central Ohio, United States, [email protected] media can be accessed here:
http://streaming.osu.edu/knowledgebank/PREA/PREA_Session13C_Pyakurel_20190326.mp
Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity
No full textAlthough expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs) of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM) in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma
Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition.
No full textTrichoplein/mitostatin (TpMs) is a keratin-binding protein that partly colocalizes with mitochondria and is often downregulated in epithelial cancers, but its function remains unclear. In this study, we report that TpMs regulates the tethering between mitochondria and endoplasmic reticulum (ER) in a Mitofusin 2 (Mfn2)-dependent manner. Subcellular fractionation and immunostaining show that TpMs is present at the interface between mitochondria and ER. The expression of TpMs leads to mitochondrial fragmentation and loosens tethering with ER, whereas its silencing has opposite effects. Functionally, the reduced tethering by TpMs inhibits apoptosis by Ca(2+)-dependent stimuli that require ER-mitochondria juxtaposition. Biochemical and genetic evidence support a model in which TpMs requires Mfn2 to modulate mitochondrial shape and tethering. Thus, TpMs is a new regulator of mitochondria-ER juxtaposition
A novel approach to evaluating sustainability of products and associated manufacturing processes
No full textDigital twinning offers a prospect of accessing enormous information about products and associated manufacturing processes by applying internet of things, artificial intelligence, and digital databases, specifically in the context of Industry 4.0. The gathered information can enable the evaluation of the degree of sustainability of any product and the associated manufacturing processes. This paper proposes such evaluation by utilizing a novel metric termed as Product Sustainability Index (PSI). Advances in smart manufacturing and digital twinning could enable collection of data needed to estimate PSI which considers environmental and societal dimensions of sustainability associated with the production processes of any product. The PSI has a potential to inform customers about the environmental impacts of the products they consume and may also be used as an evaluation and a policy tool by manufacturers and governments
Automated urinalysis: First experiences and comparison of automated urinalysis system and manual microscopy
No full textBackground: Urinary tract infection is a common condition which needs laboratory evaluation of urine to substantiate the clinical diagnosis and initiate treatment. The conventional urinalysis consists of using a test strip for chemical examination to identify the various urine sediments after which visual microscopy is done. We evaluate the analytical performance of automated microscopic technique (UF 500i) and compare results with those from manual microscopy. Materials and Methods: A total of 382 urine specimens were collected during a period of one month out of which 128 samples which had abnormal cell counts were analyzed for cells and particles by manual and automated microscopy by UF-500i flow cytometer. Results: The concordance of UF 500i and the manual microscopy which is considered to be the gold standard for urine microscopic examination was 90.6% for white blood cells, red blood cell, epithelial cells, cast and bacterial count. Conclusion: Automated urine sediment analyzer, UF 500i was considered reliable in the measurement of white blood cells, red blood cells, epithelial cells, cast and bacteria. Automation will surely reduce the work load, increase accuracy and reliability, and increase the throughput and turn-around time of the laboratory DOI: http://dx.doi.org/10.3126/jpn.v4i7.10316 Journal of Pathology of Nepal (2014) Vol. 4, 576-579 </p
PARP inhibition by olaparib or gene knockout blocks asthma-like manifestation in mice by modulating CD4+ T cell function
No full textBackground: An important portion of asthmatics do not respond to current therapies. Thus, the need for new therapeutic drugs is urgent. We have demonstrated a critical role for PARP in experimental asthma. Olaparib, a PARP inhibitor, was recently introduced in clinical trials against cancer. The objective of the present study was to examine the efficacy of olaparib in blocking established allergic airway inflammation and hyperresponsiveness similar to those observed in human asthma in animal models of the disease. Methods: We used ovalbumin (OVA)-based mouse models of asthma and primary CD4+ T cells. C57BL/6J WT or PARP-1-/- mice were subjected to OVA sensitization followed by a single or multiple challenges to aerosolized OVA or left unchallenged. WT mice were administered, i.p., 1 mg/kg, 5 or 10 mg/kg of olaparib or saline 30 min after each OVA challenge. Results: Administration of olaparib in mice 30 min post-challenge promoted a robust reduction in airway eosinophilia, mucus production and hyperresponsiveness even after repeated challenges with ovalbumin. The protective effects of olaparib were linked to a suppression of Th2 cytokines eotaxin, IL-4, IL-5, IL-6, IL-13, and M-CSF, and ovalbumin-specific IgE with an increase in the Th1 cytokine IFN-γ. These traits were associated with a decrease in splenic CD4+ T cells and concomitant increase in T-regulatory cells. The aforementioned traits conferred by olaparib administration were consistent with those observed in OVA-challenged PARP-1-/- mice. Adoptive transfer of Th2-skewed OT-II-WT CD4+ T cells reversed the Th2 cytokines IL-4, IL-5, and IL-10, the chemokine GM-CSF, the Th1 cytokines IL-2 and IFN-γ, and ovalbumin-specific IgE production in ovalbumin-challenged PARP-1-/-mice suggesting a role for PARP-1 in CD4+ T but not B cells. In ex vivo studies, PARP inhibition by olaparib or PARP-1 gene knockout markedly reduced CD3/CD28-stimulated gata-3 and il4 expression in Th2-skewed CD4+ T cells while causing a moderate elevation in t-bet and ifn-γ expression in Th1-skewed CD4+ T cells. Conclusions: Our findings show the potential of PARP inhibition as a viable therapeutic strategy and olaparib as a likely candidate to be tested in human asthma clinical trials
PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice
No full textOur laboratory established a role for poly(ADP-ribose)polymerase (PARP) in asthma. To increase the clinical significance of our studies, it is imperative to demonstrate that PARP is actually activated in human asthma, to examine whether a PARP inhibitor approved for human testing such as olaparib blocks already-established chronic asthma traits in response to house dust mite (HDM), a true human allergen, in mice and to examine whether the drug modulates human cluster of differentiation type 4 (CD4(+)) T-cell function. To conduct the study, human lung specimens and peripheral blood mononuclear cells (PBMCs) and a HDM-based mouse asthma model were used. Our results show that PARP is activated in PBMCs and lung tissues of asthmatics. PARP inhibition by olaparib or gene knockout blocked established asthma-like traits in mice chronically exposed to HDM including airway eosinophilia and hyper-responsiveness. These effects were linked to a marked reduction in T helper 2 (Th2) cytokine production without a prominent effect on interferon (IFN)-γ or interleukin (IL)-10. PARP inhibition prevented HDM-induced increase in overall cellularity, weight and CD4(+) T-cell population in spleens of treated mice whereas it increased the T-regulatory cell population. In CD3/CD28-stimulated human CD4 (+)T-cells, olaparib treatment reduced Th2 cytokine production potentially by modulating GATA binding protein-3 (gata-3)/IL-4 expression while moderately affecting T-cell proliferation. PARP inhibition inconsistently increased IL-17 in HDM-exposed mice and CD3/CD28-stimulated CD4(+) T cells without a concomitant increase in factors that can be influenced by IL-17. In the present study, we provide evidence for the first time that PARP-1 is activated in human asthma and that its inhibition is effective in blocking established asthma in mice
Leiomyoma on the penile shaft
No full textPrimary soft tissue tumors of the penis, such as leiomyomas, are very rare. To the best of our knowledge, less than ten cases have been reported till date. The lesion gradually increases in size and can mimic a malignant lesion. Excisional biopsy and histopathological examination can provide the diagnosis as well as cure, both physical and psychological. We report a case of a penile shaft leiomyoma in a 49 year old male.DOI: http://dx.doi.org/10.3126/jpn.v4i8.11598 Journal of Pathology of Nepal; Vol.4,No. 8 (2014) 680-681</p
Orchids in Rolpa district of Western Nepal: Documentation, stock, trade and conservation
No full textOrchids are perennial, epiphytic, terrestrial or lithophytic herbs with roots having multilayered spongy tissues. In Nepal, 363 species of orchids are organized into 97 genera. Orchids fall under the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) Appendix II but do not fall under the legal protection of any existing national legislation. Habitat loss, forest destruction and degradation and over-exploitation have posed threats to the conservation of orchids in Nepal. The current study aims to document the orchids and estimate the stock of Dendrobium denudans and Dendrobium eriiflorum in a few potential locations of Rolpa district. A total of 36 species were documented in the surveyed 17 Village Development Committees (VDCs). Among them, 31 species were identified up to species level, two species up to generic level and the remaining three were unidentifed. The total stock of D. denudans was highest in Uwa VDC with 11018.08 kg followed by Seram VDC with the stock of 9982.57 kg. Similarly, D. eriiflorum stock in Seram, Siuri and Jaimakasala VDCs were 22750.01 kg, 7039.67 kg and 4933.46 kg, respectively. This study recommends a systematic research on the propagation technique; complete indexing of orchids; and inclusion of orchids in the Red Data Book on the threatened and endangered species. Orchid reserves in orchid hotspots should be established for the preservation and promotion of regeneration activities. The rare and endangered species should be preserved in botanic gardens. In addition to scientific attempts, the country should launch and implement a very firm regulation for their protection. Key words: Orchids; Dendrobium denudans; Dendrobium eriiflorum; distribution; conservation; Rolpa district DOI: 10.3126/banko.v20i2.4796 Banko Janakari Vol.20(2) 2010 pp.3-13</jats:p
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