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Histamine 3 receptor activation mediates inhibition of acid secretion during Helicobacter-induced gastritis

World Journal of Gastrointestinal Pathophysiology 2010年第5期1卷 154-165页

作者： Yana Zavros Nisreen Mesiwala meghna waghray Andrea Todisco Arthur Shulkes Juanita L Merchant Departments of Internal Medicine-Gastroenterology University of Michigan Department of Molecular and Cellular Physiology University of Cincinnati Department of Surgery Austin and Repatriation Medical CenterUniversity of Melbourne Departments of Internal Medicine and Molecular and Integrative Physiology University of Michigan

AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide(THIO)for 12 wk.After treatment,mice were analyzed for morphological changes and gastric acid content.Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction(RTPCR).Location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H + ,K + -ATPase βsubunit. RESULTS:Inflammation and parietal cell atrophy was observed after 12 wk of H.felis infection.Interestingly, treatment with the H3R antagonist thioperamide(THIO) prior to and during infection prevented H.felis-induced inflammation and atrophy.Compared to the uninfected controls,infected mice also had significantly decreased gastric acid.After eradication of H.felis with THIO treatment,gastric acidity was restored.Compared to the control mice,somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection.Despite elevated gastric acid levels, after eradication of H.felis with THIO,somatostatin mRNA was elevated whereas gastrin mRNA was suppressed.Immunofluorescence revealed the presence of H3 receptors on the parietal cells,somatostatin-secreting D-cells as well as the inflammatory cells. CONCLUSION:This study shows that during H.felis infection,gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation.The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin.

关键词： Gastrin Somatostatin Histamine Parietal

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Characterization and Propagation of Historical and Projected Droughts in the Umatilla River Basin, Oregon, USA

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Advances in Atmospheric Sciences 2024年第2期41卷 247-262,I0020-I0028页

作者： Sudip GAUTAM Alok SAMANTARAY meghna BABBAR-SEBENS Meenu RAMADAS School of Civil and Construction Engineering Oregon State UniversityCorvallisOR 97331USA School of Infrastructure Indian Institute of TechnologyBhubaneswarOdisha 752050India

Climate change is expected to have long-term impacts on drought and wildfire risks in Oregon as summers continue to become warmer and drier. This paper investigates the projected changes in drought characteristics and drought propagation in the Umatilla River Basin in northeastern Oregon for mid-century(2030–2059) and late-century(2070–2099) climate scenarios. Drought characteristics for projected climates were determined using downscaled CMIP5 climate datasets from ten climate models and Soil and Water Assessment Tool to simulate effects on hydrologic processes. Short-term(three months) drought characteristics(frequency, duration, and severity) were analyzed using four drought indices, including the Standardized Precipitation Index(SPI-3), Standardized Precipitation-Evapotranspiration Index(SPEI-3), Standardized Streamflow Index(SSI-3), and the Standardized Soil Moisture Index(SSMI-3). Results indicate that short-term meteorological droughts are projected to become more prevalent, with up to a 20% increase in the frequency of SPI-3drought events. Short-term hydrological droughts are projected to become more frequent(average increase of 11% in frequency of SSI-3 drought events), more severe, and longer in duration(average increase of 8% for short-term droughts).Similarly, short-term agricultural droughts are projected to become more frequent(average increase of 28% in frequency of SSMI-3 drought events) but slightly shorter in duration(average decrease of 4%) in the future. Historically, drought propagation time from meteorological to hydrological drought is shorter than from meteorological to agricultural drought in most sub-basins. For the projected climate scenarios, the decrease in drought propagation time will likely stress the timing and capacity of water supply in the basin for irrigation and other uses.

关键词： Umatilla drought SPI SPEI SSI SSMI

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Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment

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Oncology Research 2024年第1期32卷 19-47页

作者： ABHISHEK WAHI MAMTA BISHNOI NEHA RAINA meghna AMRITA SINGH PIYUSH VERMA PIYUSH KUMAR GUPTA GINPREET KAUR HARDEEP SINGH TULI MADHU GUPTA Department of Pharmaceutics School of Pharmaceutical SciencesDelhi Pharmaceutical Sciences and Research University(DPSRU)Pushp ViharNew Delhi110017India Department of Pharmaceutical Sciences Gurugram UniversityHaryana122003India Department of Life Sciences Sharda School of Basic Sciences and ResearchSharda UniversityGreater NoidaUttar Pradesh201310India Department of Biotechnology Graphic Era(Deemed to be University)DehradunUttarakhand248002India Department of Pharmacology Shobhaben Pratapbhai Patel School of Pharmacy&Technology ManagementSVKM’s NMIMSVile Parle(West)Mumbai400056India Department of Bio-Sciences and Technology Maharishi Markandeshwar Engineering CollegeMaharishi Markandeshwar(Deemed to be University)MullanaAmbala133207India

Cancer is a leading cause of death globally,with limited treatment options and several limitations.Chemotherapeutic agents often result in toxicity which long-term conventional treatment.Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance.These phytoconstituents act in several ways and deliver optimum effectiveness against cancer.Nevertheless,the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility,bioavailability,and stability.Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems,which possess a range of advantageous characteristics such as biocompatibility,targeted and sustained release capabilities,and enhanced protective effects.This holds significant potential for future advancements in cancer management.Herein,this review aims to provide intensive literature on diverse nanocarriers,highlighting their applications as cargos for phytocompounds in cancer.Moreover,it offers an overview of the current advancements in the respective field,emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings.Lastly,clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.

关键词： Phyto-formulations Cancer Nanocarriers Nanotechnology Clinical development

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Experimental study on mitigating wind erosion of calcareous desert sand using spray method for microbially induced calcium carbonate precipitation

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Journal of Rock Mechanics and Geotechnical Engineering 2022年第5期14卷 1556-1567页

作者： Monika Dagliya Neelima Satyam meghna Sharma Ankit Garg Department of Civil Engineering Indian Institute of Technology IndoreIndoreIndia Department of Civil and Environmental Engineering Shantou UniversityShantouChina L.N.Gumilyov Eurasian National University Nur-SultanKazakhstan

Wind erosion is one of the significant natural calamities worldwide, which degrades around one-third of global land. The eroded and suspended soil particles in the environment may cause health hazards, i.***.allergies and respiratory diseases, due to the presence of harmful contaminants, bacteria, and pollens.The present study evaluates the feasibility of microbially induced calcium carbonate precipitation(MICP)technique to mitigate wind-induced erosion of calcareous desert sand(Thar desert of Rajasthan province in India). The temperature during biotreatment was kept at 36℃ to stimulate the average temperature of the Thar desert. The spray method was used for bioaugmentation of Sporosarcina(S.) pasteurii and further treatment using chemical solutions. The chemical solution of 0.25 pore volume was sprayed continuously up to 5 d, 10 d, 15 d, and 20 d, using two different concentration ratios of urea and calcium chloride dihydrate viz 2:1 and 1:1. The biotreated samples were subjected to erosion testing(in the wind tunnel) at different wind speeds of 10 m/s, 20 m/s, and 30 m/s. The unconfined compressive strength of the biocemented crust was measured using a pocket penetrometer. The variation in calcite precipitation and microstructure(including the presence of crystalline minerals) of untreated as well as biotreated sand samples were determined through calcimeter, scanning electron microscope(SEM), and energydispersive X-ray spectroscope(EDX). The results demonstrated that the erosion of untreated sand increases with an increase in wind speeds. When compared to untreated sand, a lower erosion was observed in all biocemented sand samples, irrespective of treatment condition and wind speed. It was observed that the sample treated with 1:1 cementation solution for up to 5 d, was found to effectively resist erosion at a wind speed of 10 m/s. Moreover, a significant erosion resistance was ascertained in15 d and 20 d treated samples at higher wind speeds. The calcite content percentage, thickness of crust,bulk density, and

关键词： Control wind erosion Microbially induced calcium carbonate precipitation(MICP) Surface strength Wind tunnel Calcite precipitation

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Diabetes and cognitive function:An evidence-based current perspective

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World Journal of Diabetes 2023年第2期14卷 92-109页

作者： meghna Julian Sebastian Shahanas KA Khan Joseph M Pappachan Mohammad Sadiq Jeeyavudeen School of Life Sciences Keele UniversityStoke-on-Trent ST55BGUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology and Metabolism University Hospitals of EdinburghEdinburgh EH164SAUnited Kingdom

Several epidemiological studies have clearly identified diabetes mellitus(DM)as a major risk factor for cognitive dysfunction,and it is going to be a major public health issue in the coming years because of the alarming rise in diabetes prevalence across the world.Brain and neural tissues predominantly depend on glucose as energy substrate and hence,any alterations in carbohydrate metabolism can directly impact on cerebral functional output including cognition,executive capacity,and memory.DM affects neuronal function and mental capacity in several ways,some of which include hypoperfusion of the brain tissues from cerebrovascular disease,diabetes-related alterations of glucose transporters causing abnormalities in neuronal glucose uptake and metabolism,local hyper-and hypometabolism of brain areas from insulin resistance,and recurrent hypoglycemic episodes inherent to pharmacotherapy of diabetes resulting in neuronal damage.Cognitive decline can further worsen diabetes care as DM is a disease largely self-managed by patients.Therefore,it is crucial to understand the pathobiology of cognitive dysfunction in relation to DM and its management for optimal long-term care plan for patients.A thorough appraisal of normal metabolic characteristics of the brain,how alterations in neural metabolism affects cognition,the diagnostic algorithm for patients with diabetes and dementia,and the management and prognosis of patients when they have this dangerous combination of illnesses is imperative in this context.This evidence-based narrative with the backup of latest clinical trial reviews elaborates the current understanding on diabetes and cognitive function to empower physicians to manage their patients in day-to-day clinical practice.

关键词： Diabetes mellitus Dementia Cognitive function Antidiabetic medications Hyperglycemia Hypoglycemia

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Rock-like behavior of biocemented sand treated under non-sterile environment and various treatment conditions

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Journal of Rock Mechanics and Geotechnical Engineering 2021年第3期13卷 705-716页

作者： meghna Sharma Neelima Satyam Krishna RReddy Discipline of Civil Engineering Indian Institute of Technology IndoreIndore453552India Department of Civil Materialsand Environmental EngineeringUniversity of Illinois at ChicagoChicagoILUSA

Microbially induced calcite precipitation(MICP)is a recently developed technique for microbiological ground improvement that has been applied for mitigating various geotechnical challenges.However,the major challenges,such as calcite precipitation uniformity,presence of different bacteria,cementation solution optimization for cost reduction,and implementation under non-sterile and uncontrolled field environment are still not fully explored and require detailed investigation before field application.This study aims to address these challenges of MICP to improve the geotechnical properties of sandy soils.Several series of experiments were conducted using poorly graded Narmada River(India)sand,which were subjected to various biotreatment schemes and tested for unconfined compressive strength(UCS),split tensile strength(STS),ultrasonic pulse velocity(UPV),hydraulic conductivity(after 6 d,12 d,and 18 d of treatment),and calcite content.The microstructure of sand was examined through a scanning electron microscope(SEM).Initially,the sand was individually augmented with two non-pathogenic bacterial strains,i.e.Sporosarcina(S.)pasteurii and Bacillus(B.)sphaericus.The stopped-flow injection method was adopted to provide cementation solutions at three different durations(treatment cycle)of 12 h,24 h,and 48 h and three different pore volumes(PVs)of 1,0.75,and 0.5.The pore volume here refers to the porosity which is expressed as a ratio,i.e.a porosity of 50%was used as 0.5.The results showed rock-like behaviors of biocemented sand with the UCS,STS,and UPV enhancement up to 2333 kPa,437 kPa,and 2670 m/s,respectively.The hydraulic conductivity reduction of 96.6%was achieved by 12%of calcite formation after 18 d of treatment using Sporosarcina pasteurii,12-h treatment cycle,and one pore volume of cementation media in each cycle.Overall,a 24-h treatment cycle and 0.5-pore volume cementation solution were found to be the optimal treatment which was effective and economical to achieve heavily cemented,rock-type biocemented sand us

关键词： Bacteria Microbially induced calcite precipitation (MICP) Soil stabilization Microstructure Calcite content

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Regulation of U6 Promoter Activity by Transcriptional Interference in Viral Vector-Based RNAi

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Genomics, Proteomics & Bioinformatics 2010年第3期8卷 170-179页

作者： Linghu Nie meghna Das Thakur Yumei Wang Qin Su Yongliang Zhao Yunfeng Feng Key Laboratory of Genome Sciences and Information Cancer Biology and Genetics Group Beijing Institute of Genomics Chinese Acadamy of Sciences Beijing 100029 China Departments of Medicine and Cell Biology Washington University St. Louis MO 63110 USA Immunocore Limited Abingdon Oxon OX14 4RX UK.

The direct negative impact of the transcriptional activity of one component on the second one in c/s is referred to as transcriptional interference （TI）. U6 is a type III RNA polymerase III promoter commonly used for driving small hairpin RNA （shRNA） expression in vector-based RNAi. In the design and construction of viral vectors, multiple transcription units may be arranged in close proximity in a space-limited vector. Determining if U6 promoter activity can be affected by TI is critical for the expression of target shRNA in gene therapy or loss-of-function studies. In this research, we designed and implemented a modified retroviral system where shRNA and exogenous gene expressions were driven by two independent transcriptional units. We arranged U6 promoter driving .shRNA expression and UbiC promoter in two promoter arrangements. In primary macrophages, we found U6 promoter activity was inhibited by UbiC promoter when in the divergent arrangement but not in tandem. In contrast, PKG promoter had no such negative impact. Instead of enhancing U6 promoter activity, CMV enhancer had significant negative impact on U6 promoter activity in the presence of UbiC promoter. Our results indicate that U6 promoter activity can be affected by TI in a proximal promoter-specific and arrange- ment-dependent manner.

关键词： transcriptional interference U6 promoter shRNA retrovirus

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A Multifunctional Lentiviral-Based Gene Knockdown with Concurrent Rescue that Controls for Off-Target Effects of RNAi

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Genomics, Proteomics & Bioinformatics 2010年第4期8卷 238-245页

作者： Yunfeng Feng Linghu Nie meghna Das Thakur Qin Su Zhenfen Chi Yongliang Zhao Gregory D. Longmore Departments of Medicine and Cell Biology Washington University St. Louis MO 63110 USA Key Laboratory of Genome Sciences and Information Cancer Biology and Genetics Group Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Immunocore Limited Abingdon Oxon OX14 4RX UK

The efficient, stable delivery of siRNA into cells, and the appropriate controls for non-specific off-target effects of siRNA are major limitations to functional studies using siRNA technology. To overcome these drawbacks, we have developed a single lentiviral vector that can concurrently deplete endogenous gene expression while expressing an epitope-tagged siRNA-resistant target gene in the same cell. To demonstrate the functional utility of this system, we performed RNAi-depleted α-actinin-1 （α-ACTN1） expression in human T cells. α-ACTN1 RNAi resulted in inhibited chemotaxis to SDF-1α, but it can be completely rescued by concurrent expression of RNAi-resistant α-ACTN1 （rr-α-ACTN1） in the same cell. The presence of a GFP tag on rr-α-ACTN1 allowed for detection of appropriate subcellular localization of rr-α-ACTN1. This system provides not only an internal control for RNAi off-target effects, but also the potential tool for rapid structure-function analyses and gene therapy.

关键词： lentivirus RNAi shRNA α-actinin-1 chemotaxis

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Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs

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World Journal of Gastroenterology 2007年第23期13卷 3199-3205页

作者： meghna R Adhvaryu Narsimha Reddy Minoo H Parabia Bapalal Vaidya Botanical Research Centre Department of Biosciences Veer Narmad South Gujarat University

AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ?1.68 vs 40.61 ?1.28, P < 0.01), PI (2.0725±0.05 vs 0.61±0.05, P < 0.001) and CI (1.8525±0.04 vs 0.695±0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function. CONCLUSION: All four herbs showed hepatoprotective potential and prevented immunosuppression. CL

关键词：肝中毒异烟肼利福平吡嗪酰胺

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Prevention of hepatotoxicity due to anti tuberculosis treatment: A novel integrative approach

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World Journal of Gastroenterology 2008年第30期14卷 4753-4762页

作者： meghna R Adhvaryu Narsimha M Reddy Bhasker C Vakharia Bapalal Vaidya Botanical Research Centre Department of Biosciences Veer Narmad South Gujarat University Shree Gurudev Sarvajanik Charitable Trust Mobile Clinic Ramnagar Rander Road

AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity. METHODS: Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS: Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P < 0.0001). Mean aspartate transaminase (AST) (195.93 ± 108.74 vs 85 ± 4.24, P < 0.0001), alanine transaminase (ALT) (75.74 ± 26.54 vs 41 ± 1.41, P < 0.0001) and serum bilirubin (5.4 ± 3.38 vs 1.5 ± 0.42, P < 0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P = 0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P= 0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P < 0.0001). CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.

关键词：肝中毒抗结核治疗姜黄色素预防方法

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