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Garcinol suppresses the growth of human hepatocellular carcinoma by inducing abrogation of STAT3 phosphorylation,acetylation and dimerization

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中国药理学与毒理学杂志 2015年第S1期29卷 82-83页

作者： Muthu K SHANMUGAM Snehajyoti CHATTERJEE Peramaiyan RAJENDRAN Feng LI parijat senapati Kwong Fai WONG Alan Prem KUMAR John MLUK Kam Man HUI Gautam SETHI Tapas K KUNDU Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117957 Jawaharlal Nehru Centre for Advanced Scientific Research Molecular Biology and Genetics Unit Transcription and Disease Laboratory Jakkur P.O. Bangalore 560064 India Cancer Science Institute of Singapore National University of Singapore Singapore 117456 School of Biomedical Sciences Faculty of Health Sciences Curtin University Western Australia Division of Cellular and Molecular Research Humphrey Oei Institute of Cancer Research National Cancer Centre Singapore 169610 Institute of Molecular and Cell Biology Singapore 138673

OBJECTIVE Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide and the third cause of global cancer *** of signal transducer and activator of transcription 3(STAT3)is commonly observed in tumor cells and is a critical mediator of on cogenic signaling in HCC and controls the expression of several genes involved in proliferation,survival,metastasis and *** drug-targeted therapies,besides being expensive,are associated with serious side effects and ***,novel agents that can suppress STAT3 activation have potential for both prevention and treatment of *** the present report,we investigated whether the potent HAT/KAT inhibitor,garcinol,(apolyisoprenylatedbenzophenone),could suppress STAT3 activation in HCC cells and in nude mice *** The effect of garcinol on HCC cell lines wasdetermined by MTT assay,immunoblotting,DNA binding assays,immuno-fluorescenceand immune-histochemical *** effect of garcinolon the inhibition of tumor growth in vivo was also investigated using HCCxenograft tumor modelin athymic nu/nu *** We found that garcinol could inhibit constitutive STAT3 activation in a dose-and time-dependent manner both by inhibiting STAT3 phosphorylation and acetylation in HCC *** investigated for molecular mechanism(s),we found that garcinol interferes with the dimer formation of STAT3 thereby inhibits its nuclear *** modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppresses its dimerization in *** understand the cellular mechanism(s)of inhibition of STAT3 function by garcinol,we observed that upon inhibition of STAT3 dimerization bygarcinol,STAT3 DNA binding ability gets *** inhibition of STAT3 activation by garcinol led to the suppression of various gene products involved in proliferation,survival,and ***,when administered i.p.,garcinol inhibited the growth of human HCC xenograft tumors in

关键词： STAT3 HCC garcinol acetylation dimerization nude m

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Establishing the relationship between land use land cover,normalized difference vegetation index and land surface temperature:A case of Lower Son River Basin,India

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Geography and Sustainability 2024年第2期5卷 265-275页

作者： Shipra Singh Pankaj Kumar Rakhi parijat Barbaros Gonengcil Abhinav Rai Department of Geography Miranda HouseUniversity of DelhiDelhiIndia Department of Geography Delhi School of EconomicsUniversity of DelhiDelhiIndia Department of Geography Istanbul UniversityIstanbulTurkey

The study explores the intricate interplay between land use land cover(LULC),normalized difference vegetation index(NDVI),and land surface temperature(LST)within the Lower Son River Basin in India from 1991 to *** region’s ecological balance has been increasingly strained due to rapid urbanization and changing land use *** a combination of Landsat TM&OLI/TIRS satellite imageries and geospatial analysis techniques,this study unveils the intricate connection between land use and land cover changes,vegetation,and land surface temperature *** study area is classified into three altitudinal zones(Zone Ⅰ:39–300 m,Zone Ⅱ:301–600 m and Zone Ⅲ:601–1,247 m)to examine the changes in *** area has seen significant changes in LULC,vegetation and LST in all the three altitudinal *** findings hold significant implications for sustainable land management and environmental conservation strategies in the Lower Son River *** per the result,103,438 ha of vegetation was converted into agriculture land and 82,572 ha of agricultural land was transformed into settlements from 1991 to *** trend shows human pressure on the land resource in the study *** increase in water body is seen which is attributed to commissioning of Bansagar *** Ⅰ has seen highest settlement growth while Zone Ⅲ experienced severe deforestation of around 15%.Zone Ⅱ and Ⅲ needs attention for holistic *** of LST shows that it has increased by 0.82℃ from 1991 to 2020 which is a red *** study underscores the critical importance of balanced land use practices to preserve ecological integrity and mitigate the adverse effects of urbanization and climate change.

关键词： Lower Son River Basin LULC LST NDVI Correlation

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GUARDIAN: A Multi-Tiered Defense Architecture for Thwarting Prompt Injection Attacks on LLMs

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Journal of Software Engineering and Applications 2024年第1期17卷 43-68页

作者： parijat Rai Saumil Sood Vijay K. Madisetti Arshdeep Bahga School of Computer Science Engineering & Technology Bennett University Greater Noida India School of Cybersecurity and Privacy Georgia Institute of Technology Atlanta USA Cloudemy Technology Labs Chandigarh India

This paper introduces a novel multi-tiered defense architecture to protect language models from adversarial prompt attacks. We construct adversarial prompts using strategies like role emulation and manipulative assistance to simulate real threats. We introduce a comprehensive, multi-tiered defense framework named GUARDIAN (Guardrails for Upholding Ethics in Language Models) comprising a system prompt filter, pre-processing filter leveraging a toxic classifier and ethical prompt generator, and pre-display filter using the model itself for output screening. Extensive testing on Meta’s Llama-2 model demonstrates the capability to block 100% of attack prompts. The approach also auto-suggests safer prompt alternatives, thereby bolstering language model security. Quantitatively evaluated defense layers and an ethical substitution mechanism represent key innovations to counter sophisticated attacks. The integrated methodology not only fortifies smaller LLMs against emerging cyber threats but also guides the broader application of LLMs in a secure and ethical manner.

关键词： Large Language Models (LLMs) Adversarial Attack Prompt Injection Filter Defense Artificial Intelligence Machine Learning Cybersecurity

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Evaluating Privacy Leakage and Memorization Attacks on Large Language Models (LLMs) in Generative AI Applications

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Journal of Software Engineering and Applications 2024年第5期17卷 421-447页

作者： Harshvardhan Aditya Siddansh Chawla Gunika Dhingra parijat Rai Saumil Sood Tanmay Singh Zeba Mohsin Wase Arshdeep Bahga Vijay K. Madisetti School of Computer Science Engineering & Technology Bennett University Greater Noida India Cloudemy Technology Labs Chandigarh India School of Cybersecurity and Privacy Georgia Institute of Technology Atlanta USA

The recent interest in the deployment of Generative AI applications that use large language models (LLMs) has brought to the forefront significant privacy concerns, notably the leakage of Personally Identifiable Information (PII) and other confidential or protected information that may have been memorized during training, specifically during a fine-tuning or customization process. We describe different black-box attacks from potential adversaries and study their impact on the amount and type of information that may be recovered from commonly used and deployed LLMs. Our research investigates the relationship between PII leakage, memorization, and factors such as model size, architecture, and the nature of attacks employed. The study utilizes two broad categories of attacks: PII leakage-focused attacks (auto-completion and extraction attacks) and memorization-focused attacks (various membership inference attacks). The findings from these investigations are quantified using an array of evaluative metrics, providing a detailed understanding of LLM vulnerabilities and the effectiveness of different attacks.

关键词： Large Language Models PII Leakage Privacy Memorization Overfitting Membership Inference Attack (MIA)

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Endophytic fungi harbored in Cannabis sativa L.:diversity and potential as biocontrol agents against host plant-specific phytopathogens

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Fungal Diversity 2013年第3期60卷 137-151页

作者： parijat Kusari Souvik Kusari Michael Spiteller Oliver Kayser Department of Biochemical and Chemical Engineering Chair of Technical BiochemistryTU DortmundEmil-Figge-Str.6644227 DortmundGermany Institute of Environmental Research(INFU)of the Faculty of Chemistry Chair of Environmental Chemistry and Analytical ChemistryTU DortmundOtto-Hahn-Str.644221 DortmundGermany

The objective of the present work was isolation,phylogenetic characterization,and assessment of biocontrol potential of endophytic fungi harbored in various tissues(leaves,twigs,and apical and lateral buds)of the medicinal plant,Cannabis sativa L.A total of 30 different fungal endophytes were isolated from all the plant tissues which were authenticated by molecular identification based on rDNA ITS sequence analysis(ITS1,5.8S and ITS2 regions).The Menhinick’s index revealed that the buds were immensely rich in fungal species,and Camargo’s index showed the highest tissue-specific fungal dominance for the *** most dominant species was Penicillium copticola that could be isolated from the twigs,leaves,and apical and lateral buds.A detailed calculation of Fisher’s log series index,Shannon diversity index,Simpson’s index,Simpson’s diversity index,and Margalef’s richness revealed moderate overall biodiversity of *** endophytes distributed among its *** fungal endophytes were challenged by two host phytopathogens,Botrytis cinerea and Trichothecium roseum,devising a dual culture antagonistic assay on five different *** observed 11 distinct types of pathogen inhibition encompassing a variable degree of antagonism(%)on changing the *** revealed the potential chemodiversity of the isolated fungal endophytes not only as promising resources of biocontrol agents against the known and emerging phytopathogens of Cannabis plants,but also as sustainable resources of biologically active and defensive secondary metabolites.

关键词： Cannabis sativa Endophytic fungi Fungal diversity Antagonism Botrytis cinerea Trichothecium roseum

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Natural history and management of liver dysfunction in lysosomal storage disorders

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World Journal of Hepatology 2022年第10期14卷 1844-1861页

作者： Moinak Sen Sarma parijat Ram Tripathi Department of Pediatric Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014India Department of Pediatric Gastroenterology Ankura Hospital for Women and ChildrenHyderabad 500072India

Lysosomal storage disorders(LSD)are a rare group of genetic *** major LSDs that cause liver dysfunction are disorders of sphingolipid lipid storage[Gaucher disease(GD)and Niemann-Pick disease]and lysosomal acid lipase deficiency[cholesteryl ester storage disease and Wolman disease(WD)].These diseases can cause significant liver problems ranging from asymptomatic hepatomegaly to cirrhosis and portal *** storage cells initiate hepatic fibrosis in sphingolipid *** causes micronodular cirrhosis in lipid storage *** disorders must be keenly differentiated from other chronic liver diseases and non-alcoholic steatohepatitis that affect children and young ***,Niemann-Pick type C,and WD also cause neonatal cholestasis and infantile liver *** and liver phenotype correlation is variable in these *** with LSD may survive up to 4-5 decades except for those with neonatal onset *** diagnosis of all LSD is based on enzymatic activity,tissue histology,and genetic *** replacement is possible in GD and Niemann-Pick types A and B though there are major limitations in the *** that progress invariably require liver transplantation with variable *** prognosis of Niemann-Pick type C and WD is universally *** replacement therapy has a promising role in cholesteryl ester storage *** review attempts to outline the natural history of these disorders from a hepatologist’s perspective to increase awareness and facilitate better management of these rare disorders.

关键词： Lysosomal Gaucher Niemann-Pick Wolman Cholesteryl ester Children

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Corrosive upper gastrointestinal strictures in children:Difficulties and dilemmas

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World Journal of Clinical Pediatrics 2021年第6期10卷 124-136页

作者： Moinak Sen Sarma parijat Ram Tripathi Sachin Arora Department of Pediatric Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia Department of Pediatric Gastroenterology Ankura Hospsital for Women and ChildrenHyderabad 500072TelanganaIndia Department of Surgical Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia

Children constitute 80%of all corrosive ingestion *** majority of this burden is contributed by developing *** ingestion is common in younger children(<5 years)while suicidal ingestion is more common in *** severity of injury depends on nature of corrosive(alkali or acid),pH,amount of ingestion and site of *** are multiple doubts and dilemmas which exist in management of both acute ingestion and chronic *** ingestion leads to skin,respiratory tract or upper gastrointestinal damage which may range from trivial to life threatening *** is an important early investigation to decide for further course of *** use of steroids for prevention of stricture is a debatable *** gastrointestinal stricture is a common longterm sequelae of severe corrosive injury which usually develops after three weeks of *** cornerstone of management of esophageal strictures is endoscopic bougie or balloon *** case of resistant strictures,newer adjunctive therapies like intralesional steroids,mitomycin and stents can be utilized along with endoscopic *** is the final resort for strictures resistant to endoscopic dilatations and adjunctive *** is no consensus on best esophageal replacement *** strictures require balloon dilatation,failure of which requires *** with post-corrosive strictures should be kept in long term follow-up due to significantly increased risk of *** all the endoscopic and surgical options available,management of corrosive stricture in children is a daunting task due to high chances of recurrence,perforation and complications related to poor nutrition and surgery.

关键词： Corrosive Stricture Children Endoscopic dilatation Adjunctive therapy Surgery

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Cysticercosis of the eye

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International Journal of Ophthalmology(English edition) 2017年第8期10卷 1319-1324页

作者： Rebika Dhiman Saranya Devi Kavitha Duraipandi parijat Chandra Murugesan Vanathi Radhika Tandon Seema Sen Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi 110029 India

Cysticercosis is a preventable and eradicable cause of blindness endemic in the Indian subcontinent, South- East Asia and other developing countries. Ocular and orbital cysticercosis has varied presentations depending upon the site of involvement, number of lesion and the host immune response. In this article we present a review of the various clinical manifestations, diagnosis and management protocol for orbital and ocular cysticercosis. Owing to its varied presentation, cysticercosis may pose a diagnostic challenge to the health professionals. Early diagnosis and management can prevent the vision loss and optimize visual outcomes.

关键词： cysticercosis orbital cysticercosis ocular cysticercosis intracameral cysticercosis

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Organic–inorganic nanohybrids for fluorescence, photoacoustic and Raman bioimaging

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Science Bulletin 2015年第7期60卷 665-678,M0003页

作者： Sivaramapanicker Sreejith Tran Thi Mai Huong parijat Borah Yanli Zhao Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University School of Materials Science and Engineering Nanyang Technological University

Organic-inorganic nanohybrid materials repre- sent a wide range of nanoscaled synthetic materials con- sisting of both organic and inorganic components that are linked together by covalent or non-covalent interactions, which have been widely employed in various fields such as optoelectronics, catalysis and biomedicine. As a result of this special combination, nanohybrid materials assemble numerous extraordinary features that provide great opportunities to improve their stability, multifunctions, biocom- patibility, eco-friendliness and other physical and mechanical properties. This review highlights recent re- search developments of functional organic-inorganic nanohybrid materials and their specific applications in bioimaging including fluorescent, Raman, photoacoustic and combined bioimaging. Future research directions and perspectives in this rapidly developing field are also discussed.

关键词： Bioimaging Combined imagingFunctional nanomaterials Organic-inorganichybrid Photoacoustic imaging

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Clinical Implications and Management of Sub Clinical Hyperthyroidism: A Review

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Open Journal of Endocrine and Metabolic Diseases 2012年第3期2卷 27-35页

作者： parijat De Terence Pang Gautam Das Department of Endocrinology City Hospital Birmingham UK Department of Endocrinology University Hospital of Wales Cardiff UK

Sub clinical hyperthyroidism (SCH) is characterized by normal free thyroid hormone concentrations along with a low or undetectable serum TSH (thyrotropin) level. The increased use of TSH as a screening measure and improved assay sensitivity is contributing to the diagnosis of sub clinical hyperthyroidism more frequently than ever in our clinical practise leading to the increased prevalence of the disease. The significance of SCH remains uncertain for most patients as some will revert to normal thyroid status over time whereas others will either remain static or progress to overt thyroid disease in the future. The detrimental effects of a persistently suppressed TSH has now been extensively studied and its effect on the cardiovascular system, the skeleton, mood disturbance, quality of life is quite significant leading to considerable morbidity and mortality. Majority of the patients are asymptomatic and lack overt features but the relevance of treatment is more focussed in elderly patients where the risk of developing cardiac arrhythmia and loss of bone mineral density is much more than young people in whom a conservative approach is usually preferred. The issue is contentious, the situation is challenging and the benefits of treatment are debatable. The consensus for who, when and how to treat is growing but still hasn’t been universally accepted. We attempt to review the recent literature available for sub clinical hyperthyroidism and suggest an analytical approach to its investigations and management.

关键词： Sub Clinical Hyperthyroid Cardiovascular Skeleton Arrhythmia

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