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Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2885-2900页

作者： Porkizhi Arjunan Durga Kathirvelu Gokulnath Mahalingam ashish Kumar goel Uday George Zacharaiah Alok Srivastava Srujan Marepally Center for Stem Cell Research(A Unit of inStem Bengaluru)Christian Medical College CampusBagayamVellore 632002Tamil NaduIndia Manipal academy for higher education Mangalore 576104KarnatakaIndia Department of Hematology Christian Medical College&HospitalVellore 632004Tamil NaduIndia Department of Hepatology Christian Medical College&HospitalVellore 632004Tamil NaduIndia

Inherited genetic disorders of the liver pose a significant public health *** transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive *** overcome these limitations,nucleic acid therapy provides a hopeful alternative that enables gene repair,gene supplementation,and gene silencing with suitable *** viral vectors are the most efficient and preferred for gene therapy,pre-existing immunity debilitating immune responses limit their *** a potential alternative,lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms,including pDNA,mRNA,siRNA,and ***,we discuss the broader applications of lipid nanoparticles,from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing,as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

关键词： Lipid nanoparticle Liver disorders Gene therapy Gene editing Nucleic acid delivery pDNA mRNA siRNA ASO Clinical trials

Neuroendocrine neoplasms of liver-A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification

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World Journal of Gastroenterology 2016年第40期22卷 8956-8966页

作者： Deepak Kalyansingh Burad Thomas Alex Kodiatte Sayd Mohamed Rajeeb ashish goel Chundamannil Eapen Eapen Banumathi Ramakrishna Department of Pathology Christian Medical College Department of Hepatology Christian Medical College

AIM To study the clinicopathological characteristics of neuroendocrine neoplasms(NEN) on liver samples and apply World Health Organization(WHO) 2010 grading of gastroenteropancreatic(GEP) *** Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2(discordant 1/2) and D2/3(discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period(December 2015) were *** Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years(range 10-82 years). The most common presentation was abdominal pain(81%). Pancreas(49%) was the most common site of primary followed by gastrointestinal tract(24.4%) and lungs(18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo(range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these *** Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifo

关键词： Liver Neuroendocrine neoplasms Ki-67 Gastroenteropancreatic neuroendocrine neoplasms Metastasis Microvascular invasion

Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn’s disease in Indian

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World Journal of Gastrointestinal Pathophysiology 2022年第4期13卷 114-123页

作者： Kaushik Chatterjee Amit Kumar Dutta ashish goel Rekha Aaron Vijayalekshmi Balakrishnan Ajith Thomas Anoop John Rajeeb Jaleel Deepu David Reuben Thomas Kurien SD Chowdhury Ebby George Simon AJ Joseph Prasanna Premkumar Anna B Pulimood Department of Gastrointestinal Sciences Christian Medical College and HospitalVellore 632004Tamil NaduIndia Department of Gastroenterology Christian Medical CollegeVellore 632004Tamil NaduIndia Departments of Biostatistics Christian Medical CollegeVellore 632004Tamil NaduIndia

BACKGROUND Multiple genetic risk factors for Crohn’s disease(CD)have been ***,these observations are not consistent across different *** protein tyrosine phosphate non-receptor type 2(PTPN2)gene plays a role in various aspects of host defense including epithelial barrier function,autophagy,and innate and adaptive immune *** common polymorphisms in the PTPN2 gene(rs2542151 and rs7234029)have been associated with risk of CD in Western *** To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian *** We conducted a prospective case-control *** with CD were recruited,and their clinical and investigation details were *** were patients without organic gastrointestinal disease or other comorbid *** common polymorphisms in the PTPN2 gene(rs2542151 and rs7234029)were *** was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of *** amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length *** frequency of alleles was *** frequencies of genotypes and alleles were compared between cases and controls to look for significant *** A total of 108 patients with CD(mean age 37.5±12.7 years,females 42.6%)and 100 controls(mean age 39.9±13.5 years,females 37%)were *** the single nucleotide polymorphism(SNP)rs7234029,the overall frequency of G variant genotype(AG or GG)was noted to be significantly lower in the cases compared to controls(35.2%vs 50%,P=0.05).For the SNP rs2542151,the overall frequency of G variant genotype(GT or GG)was noted to be similar in cases compared to controls(43.6%vs 47%,P=0.73).There were no significant differences in minor allele(G)frequency for both polymorphisms between the cases and *** the SNPs had no significant association with a

关键词： PTPN2 gene Crohn’s disease Genetic polymorphism Case-control study Asia Risk factor

Characteristics and distinct prognostic determinants of individuals with hepatosplenic T-cell lymphoma over the past two decades

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World Journal of Clinical Oncology 2024年第6期15卷 745-754页

作者： Ayrton Bangolo Pierre Fwelo Shraboni Dey Tanni Sethi Sowmya Sagireddy Jawaria Chatta ashish goel Sneha Nagpaul Eric Pin-Shiuan Chen Chiranjeeve Saravanan Sheeja Gangan Joel Thomas Sarah Potiguara Vignesh K Nagesh Daniel Elias Charlene Mansour Prajakta H Ratnaparkhi Priyanshu Jain Midhun Mathew Taylor Porter Shadiya Sultan Shailaja Abbisetty Linh Tran Megha Chawla Abraham Lo Simcha Weissman Christina Cho Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Epidemiology Human Geneticsand Environmental SciencesUTHealth School of Public HealthHoustonTX 77030United States Department of Medicine Palisades Medical CenterNorth BergenNJ 07047United States Stem Cell Transplantation and Cellular Therapy John Theurer Cancer CenterHackensackNJ 07601United States

BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin *** its rarity,the true incidence of HSTCL is unknown and most data have been extrapolated through case *** the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014,with a sample size of 122 *** To paint the most updated epidemiological picture of *** A total of 186 patients diagnosed with HSTCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End Results *** analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of *** with a P value<0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic *** Overall,the outlook for this rare malignancy is very *** this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher *** data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.

关键词： Extra nodal lymphoma Mortality Survival Racial disparity Age

Preoperative therapy in locally advanced esophageal cancer

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World Journal of Gastroenterology 2016年第39期22卷 8750-8759页

作者： Pankaj Kumar Garg Jyoti Sharma ashish Jakhetiya Aakanksha goel Manish Kumar Gaur Department of Surgery University College of Medical Sciences and Guru Teg Bahadur Hospital University of Delhi Department of Surgical Oncology Sawai Man Singh Medical College Department of Surgical Oncology Dr BRA Institute Rotary Cancer Hospital All India Institute of Medical Sciences

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer(T2 or greater or node positive); however, a high rate of disease recurrence(systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment(preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy(radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

关键词： Esophageal cancer Preoperative therapy Multimodality treatment Chemotherapy Radiotherapy Chemoradiotherapy

Solar rooftop in India: Policies,challenges and outlook

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Green Energy & Environment 2016年第2期1卷 129-137页

作者： Malti goel Science & Technological Solutions for Sustainable Energy Future Climate Change Research Institute

Solar photovoltaic rooftop has emerged as a potential green technology to address climate change issues by reducing reliance on conventional fossil fuel based energy. With a strong commitment to increase the renewable sources based energy capacity to 175 GW by 2022, India has a target to install 100 GW of solar energy capacity. Of this 40 GW would be the share of grid connected solar PV rooftop. This paper examines global growth in solar energy, world's major rooftop installed capacity countries' policies and solar rooftop policy instruments in India. The current Indian goals, issues & challenges in achieving them and trends in further development are discussed.

关键词： Solar energy India Rooftop PV Policies Outlook

Experimental investigation on mechanical properties of binary and ternary blended pervious concrete

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Frontiers of Structural and Civil Engineering 2020年第1期14卷 229-240页

作者： Rekha SINGH Sanjay goel Department of Civil Engineering I.K.Gujral Punjab Technical UniversityJalandhar 144603India Department of Civil Engineering DAV Institute of Engineering and TechnologyJalandhar 144008India

The purpose of the investigation was to study the effect of binary and ternary blends of cement on the mechanical properties of pervious concrete(PC)specimen through destructive(DT)and non-destructive testing(NDT).Various combinations of fly ash(FA),limestone powder(LP),metakaolin(MK),and silica fume(SF)as mineral admixtures have been investigated to partially replace the cement up to 30%by weight in *** cube specimens of size 150 mm×150 mm×150 mm of binary and ternary blends of mineral admixture of pervious concrete were prepared to conduct standard compressive strength test and split tensile test at 7 and 28 days of *** ultrasonic pulse velocity(UPV)test and Rebound Hammer test were used as a non-destructive testing tool to substantiate the robustness of PC and to determine the approximate mechanical properties where other destructive testing tools are not feasible in case of inplace pervious *** the pervious concrete made with LP based ternary blends(PLM and PLS)were found to perform better than FA based ternary blends(PFM and PFS)and control mix(PC)in destructive and non-destructive testing.

关键词： mineral admixture ternary compressive strength split tensile strength pervious concrete ultrasonic pulse velocity

Role of gemcitabine and cisplatin as neoadjuvant chemotherapy in muscle invasive bladder cancer: Experience over the last decade

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Asian Journal of Urology 2019年第3期6卷 222-229页

作者： Sunny goel Rahul J.Sinha Ved Bhaskar Ruchir Aeron ashish Sharma Vishwajeet Singh Department of Urology King George Medical UniversityLucknowIndia

Objective:Neoadjuvant chemotherapy followed by radical cystectomy is considered the standard of care for patients with muscle invasive bladder *** the last decade,interest in neoadjuvant chemotherapy has slowly shifted from methotrexate,vinblastine,doxorubicin and cisplatin regime to gemcitabine and cisplatin *** are many publications on gemcitabine and cisplatin regime in literature which cover different aspects of *** review aims to summarise the findings published so far on gemcitabine and cisplatin regime and present it in a concise ***:A systematic literature review was conducted searching the PubMeddatabase in December 2016 using the medical subject heading(MeSH)with the terms gemcitabine,cisplatin,chemotherapy,muscle invasive bladder cancer,and *** relevant studies were included and results were ***:A total of 13 studies were included which published between 2007 and *** 13 studies comprised of 754 subjects suffering from muscle invasive bladder *** proportion of male patients ranged from 60%to 86.4%and the median age ranged from 54.2 to 77.3 years in various *** pathological response(pT0)was seen in 30.0%of patients and pathological downstaging(

关键词： Muscle invasive bladder cancer Gemcitabine Cisplatin Neoadjuvant chemotherapy Radical cystectomy

Recent progress and perspective on batteries made from nuclear waste

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Nuclear Science and Techniques 2023年第3期34卷 1-8页

作者： Nirmal Kumar Katiyar Saurav goel School of Engineering London South Bank UniversityLondonSE10 AAUK University of Petroleum and Energy Studies Dehradun248007India

Sustainable energy sources are an immediate need to cope with the imminent issue of climate change the world is facing *** particular,the long-lasting miniatured power sources that can supply energy continually to power handheld gadgets,sensors,electronic devices,unmanned airborne vehicles in space and extreme mining are some of the examples where this is an acute *** is known from basic physics that radioactive materials decay over few years and some nuclear materials have their half-life until thousands of *** past five decades of research have been spent harnessing the decay energy of the radioactive materials to develop batteries that can last until the radioactive reaction ***,an emergent opportunity of industrial symbiosis to make use of nuclear waste by using radioactive waste as raw material to develop bat-teries with long shelf life presents a great opportunity for sustainable energy resource ***,the current canon of research on this topic is *** perspective draws fresh discussions on the topic while highlighting future directions in this wealthy arena of *** abstract A long-lasting miniaturised nuclear battery utilising 14C radioactive isotope as fuel.

关键词： Sustainable energy Nuclear waste battery Nano-diamond