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HISP-1 Inhibits HSv.1 Infection in Cultured v.ro Cells

Adv.nces in Bioscience and Biotechnology 2024年第4期15卷 269-288页

作者： sandra D. Adams Kev.n T. Bilyk Modukuri v. Ramani Gottumukkala v. Subbaraju Department of Biology Montclair State University Montclair USA Department of Chemistry Andhara University Visakhapatnam India

Herpes simplex v.rus-1 (HSv.1) remains a leading cause of v.ral disease worldwide and is spread by direct contact with infected lesions. There is no v.ccine against HSv.1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study v.rious hispolon compounds were analyzed to determine their antiv.ral potential against HSv.1 infections in cultured v.ro cells. To determine the effects on infectiv.ty and possible mechanisms of inhibition, the following assays were conducted. In v.tro cytotoxicity assays were conducted to determine the effect of the compounds on cell v.ability and the maximum non-cytotoxic concentrations. Antiv.ral assays measured cell v.ability, percent inhibition of infection following treatment with the compounds, and the effect on the v.ral infection cycle. These effects were v.sualized using inv.rted light and fluorescent microscopy. Of the 24 hispolons tested, only hispolon pyrazole-1 (HISP-1) demonstrated antiv.ral effects. HISP-1 was demonstrated to effect early stages in HSv.1 infection in cultured v.ro cells (attachment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and v.ral glycoprotein D (gD). HISP-1 is safe at concentrations tested and is effectiv. in inhibiting infection of HSv.1 in cultured cells. HISP-1 has potential for therapeutic use as an antiv.ral against HSv.1 infection, could work in synergy with other antiv.rals that work be a different modality, and could be dev.loped as a component of a topical agent to reduce the spread of HSv.1 infections.

关键词： Hispolon Herpes Simplex v.rus-1 Antiv.ral Curcumin

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Antimicrobial properties of sea anemone Anthopleura nigrescens from Pacific coast of Costa Rica

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Asian Pacific Journal of Tropical Biomedicine 2016年第5期6卷 418-421页

作者： Henry Borbn sandra v.ldes Jav.er Alv.rado-Mesn Roy Soto Ilena v.ga Laboratory of Research and Dev.lopment in Chemical Technology Department of ChemistryNational University Laboratory of Biochemistry and Biotechnology of Proteins Department of Biological ScienceNational University Laboratory of Natural Products and Biological Essays Department of ChemistryNational University

Objectiv.: To ev.luate the antimicrobial and antifungal activ.ties of the aqueous and partitioned extract of sea anemone Anthopleura nigrescens(A. nigrescens).Methods: The sea anemone A. nigrescens was collected, minced, homogenized,lyophilized and then further partitioned with diethyl ether, acetone, ethanol and *** fractions were ev.luated for antimicrobial activ.ty against bacterial and fungal ***: Acetone extract was found to produce a pronounced inhibition of 7.0 mm against Proteus v.lgaris and diethyl ether extract inhibited Pseudomonas aeruginosa with an inhibition zone of 6.5 mm. In antifungal activ.ty, ethanol extract showed good activ.ty against Botrytis cinerea, Trichoderma harzianum and Rhizopus oryzae compared with other strains. Acetone and ethanol extract of A. nigrescens showed activ.ty against all of pathogens tested. Slight activ.ty was observ.d in the water extract with inhibition zone of 1.5 ***: The present study rev.aled that sea anemone A. nigrescens may also contain some biologically activ. agents which hav. potential activ.ty against pathogenic microorganisms.

关键词： Biological activ.ty Antibacterial Antifungal Bioactiv. Sea anemone

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Targeting KRAS in pancreatic cancer

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Oncology Research 2024年第5期32卷 799-805页

作者： sandra STICKLER BARBARA RATH GERHARD HAMILTON Institute of Pharmacology Medical University of ViennaViennaA-1090Austria

Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient *** Kirsten rat sarcoma v.rus(KRAS)oncogene is mutated in up to 90%of all pancreatic ductal adenocarcinomas(PDACs)and constitutes an attractiv. target for ***,the most common KRAS mutations in PDAC are G12D(44%),G12v.34%)and G12R(20%)that are not amenable to treatment by KRAS G12C-directed cysteine-reactiv. KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung *** G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is detected only in 2%–3%of ***,the KRAS G12D-directed MRTX1133 inhibitor has entered clinical trials and more of such inhibitors are in *** other KRAS mutations may be targeted indirectly v.a inhibition of the cognate guanosine exchange factor(GEF)Son of Sev.nless 1 that driv.s *** agents seem to prov.de the means to target the most frequent KRAS mutations in PDAC and to improv. patient outcomes.

关键词： Pancreatic cancer PDAC KRAS SOS1 PROTAC

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Non-alcoholic fatty liv.r disease and obesity: Biochemical, metabolic and clinical presentations

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World Journal of Gastroenterology 2014年第28期20卷 9330-9337页

作者： sandra Milic Dav.rka Lulic Dav.r Stimac Div.sion of Gastroenterology Department of Internal MedicineUniversity Hospital Rijeka

Non-alcoholic fatty liv.r disease (NAFLD) is the most common liv.r disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m2. Howev.r, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of v.sceral adipose tissue (v.T) in morbidly obese (BMI > 40 kg/m2) indiv.duals contributes to a high prev.lence of NAFLD. Free fatty acids deriv.d from v.T tissue, as well as from dietary sources and de nov. lipogenesis, are released to the portal v.nous system. Excess free fatty acids and chronic low-grade inflammation from v.T are considered to be two of the most important factors contributing to liv.r injury progression in NAFLD. In addition, secretion of adipokines from v.T as well as lipid accumulation in the liv.r further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activ.ted by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, ev.n though some may present with fatigue, dyspepsia, dull pain in the liv.r and hepatosplenomegaly. Treatment for NAFLD and NASH inv.lv.s weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article rev.ews the av.ilable information on the biochemical and metabolic phenotypes associated with obesity and fatty liv.r disease. The relativ. contribution of v.sceral and liv.r fat to insulin resistance is discussed, and recommendations for clinical ev.luation of affected indiv.duals is prov.ded.

关键词： Fatty liv.r Insulin resistance Intra-abdominal fat Metabolism Non-alcoholic fatty liv.r disease Obesity

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Risk of malignancy in Caroli disease and syndrome: A systematic rev.ew

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World Journal of Gastroenterology 2020年第31期26卷 4718-4728页

作者： Rene Fahrner sandra GC Dennler Daniel Inderbitzin Department of Surgery Bürgerspital SolothurnSolothurn 4500Switzerland Department of Surgery University Hospital DresdenDresden 01307Germany

BACKGROUND Congenital intrahepatic bile duct dilatation without fibrosis is called Caroli disease(CD),and is called Caroli syndrome(CS)when it has fibrotic and cirrhotic liv.r *** dev.lopment of intrahepatic carcinoma is described in both conditions,but the reported incidence v.ries *** risk factors for the malignant transformation were not ***,conserv.tiv. or surgical treatment is performed depending on the extent of cystic malformation,hepatic dysfunction and structural hepatic changes,but little is known about which treatment should be offered to patients with CD or CS and *** To further inv.stigate the malignant transformation in these *** A systematic rev.ew of the current literature until January 2019 was performed according to the Preferred Reporting Items for Systematic Rev.ews and Meta-Analyses statement.A search using Medline(PubMed)was performed using a combination of Medical Subject Headings terms“caroli disease”,“caroli syndrome”,“tumor”,“malignant”,and“cholangiocarcinoma”.Only human studies published in English were used for this systematic *** following parameters were extracted from each article:year of publication,type of study,number of patients,incidence of malignant tumor,duration of symptoms,age,sex,diagnostics,identification of tumor,surgical therapy,surv.v.l and tumor *** Twelv. retrospectiv. studies reporting the courses of 561 patients(53%females)were included in this systematic *** a mean age of 41.6 years old(range 23 to 56 years old),patients were younger than other populations undergoing liv.r *** on the size of the study population the incidence of cholangiocarcinoma v.ried from 2.7%to 37.5%with an ov.rall incidence of 6.6%.There were only few detailed reports about preoperativ. diagnostic work-up,but a multimodal work-up including ultrasound of the liv.r,computed tomography,magnetic resonance imaging and endoscopic retrograd

关键词： Malignancy Caroli disease Caroli syndrome Tumor Cholangiocarcinoma Rev.ew

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Colorectal cancer v.ccines: Tumor-associated antigens v. neoantigens

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World Journal of Gastroenterology 2018年第48期24卷 5418-5432页

作者： sandra Wagner Christina S Mullins Michael Linnebacher Section of Molecular Oncology and Immunotherapy General SurgeryUniversity Medical Center

Therapeutic options for the treatment of colorectal cancer(CRC) are div.rse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improv.ment in treatment outcome could be achiev.d by dev.lopment of efficient patient-indiv.dual CRC v.ccination strategies. This mini-rev.ew summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a v.riety of clinical studies examined the efficacy of different TAA-deriv.d peptide v.ccines. Combinations of sev.ral TAAs as the next step and the dev.lopment of personalized TAA-based peptide v.ccines are discussed. Improv.ments of peptidebased v.ccines achiev.ble by adjuv.nts and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusiv.ly neoantigens-which rev.aled promising results; particularly no sev.re adv.rse ev.nts were reported so far. Critical progress for clinical outcomes can be expected by indiv.dualizing neoantigen-based peptide v.ccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest dev.lopments, truly personalized neoantigen-based peptide v.ccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

关键词： Cancer v.ccines Colorectal neoplasm Immunotherapy Neoplasm antigen tumor-associated antigens tumor-specific antigens Neoantigen(s)

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Treatment of hepatitis B v.rus infection in children and adolescents

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World Journal of Gastroenterology 2021年第36期27卷 6053-6063页

作者： Mariangela Stinco Chiara Rubino sandra Trapani Giuseppe Indolfi Department of Health Sciences Pediatric SectionMeyer Children’s University HospitalFlorence 50139Italy Department Neurofarba University of Florence and Meyer Children’s University HospitalFlorence 50139Italy

Hepatitis B v.rus(HBv.infection is one of the main causes of morbidity and mortality *** children acquire the infection perinatally or during early childhood and dev.lop a chronic hepatitis characterized by a high v.ral replication and a low-inflammation phase of infection,with normal or only slightly raised *** a conserv.tiv. approach in children is usually recommended,different therapies exist and different therapeutic approaches are *** main goals of antiv.ral treatment for children with chronic HBv.infection are to suppress v.ral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in *** United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)hav. approv.d interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamiv.dine for children aged 3 years and older,entecav.r for use in children aged 2 years and older,and adefov.r for use in those 12 years of age and *** disoproxil fumarate is approv.d by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and ***,EMA has approv.d the use of tenofov.r alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of *** narrativ. rev.ew will prov.de the framework for summarizing indications to antiv.ral therapy in the management of chronic HBv.infection in children and adolescents.

关键词： Hepatitis B Children Adolescents Antiv.ral therapy Tenofov.r disoproxil fumarate Entecav.r Interferon

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Cirrhosis complicating Shwachman-Diamond syndrome: A case report

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World Journal of clinical Cases 2019年第12期7卷 1456-1460页

作者： sandra M Camacho Lucille Mcloughlin Michael J Nowicki Div.sion of Pediatric Gastroenterology University of Mississippi Medical Center Jackson MS 39216 United States Div.sion of Pediatric Gastroenterology Children’s Hospital of San Antonio San Antonio TX 78207 United States

BACKGROUND The features of Shwachman-Diamond syndrome (SDS) include exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow dysfunction;an often ov.rlooked feature is hepatic inv.lv.ment. CASE SUMMARY We report a child who initially presented with failure to thriv. and mildly elev.ted transaminase lev.ls and was determined to hav. pancreatic insufficiency due to SDS. During follow-up he had persistently elev.ted transaminase lev.ls and dev.loped hepatosplenomegaly. An inv.stigation was performed to determine the etiology of ongoing liv.r injury, including a liv.r biopsy which rev.aled hepatic cirrhosis. CONclUSION Cirrhosis has rarely been reported with SDS. While many of the hepatic disorders associated with SDS improv. with age, there are rare exceptions with serious implications for long-term outcome.

关键词： Shwachman-Diamond syndrome Cirrhosis Liv.r dysfunction Case report

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Bioactiv. Compounds and Insecticidal Activ.ty of Hysterionica pinifolia, a Nativ. South American Plant

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American Journal of Plant Sciences 2022年第6期13卷 815-832页

作者： Ingrid M. Cufre Lucas E. Fabián sandra v. cl.mente Arnaldo L. Bandoni Adriana M. Broussalis Facultad de Farmacia y Bioquímica Catedra de Farmacognosia Universidad de Buenos Aires Buenos Aires Argentina CONICET Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA) Buenos Aires Argentina Facultad de Farmacia y Bioquímica Catedra de Química Medicinal Universidad de Buenos Aires Buenos Aires Argentina Facultad de Agronomía área de Producción Vegetal Orgánica Universidad de Buenos Aires Buenos Aires Argentina

Phytochemical inv.stigation of the purified fractions of the activ. dichloromethane extract of Hysterionica pinifolia (Poir.) Baker led to the identification of fiv. compounds. New acetylenic alcohol (E)-undec-3-en-5,7-diyne-1-ol (1) and three other compounds (3), (4), and (5) were reported for the first time in this species. Furthermore, forty-six components from the v.latile fraction of H. pinifolia were identified. These compounds were elucidated using 1D and 2D NMR spectroscopy as well as MS-ESI and GC-FID-MS experiments. The dichloromethane extract, its fractions, and the methanolic extract were tested for insecticidal activ.ty against Tribolium castaneum under laboratory conditions. The dichloromethane extract and the fraction F2 were found to be activ., showing high larv.l mortality. The dichloromethane extract was also activ. against T. castaneum adults. The results hav. shown that H. pinifolia could be considered, in a near future, as a potential source for the dev.lopment of a botanical insecticide for pest control.

关键词： Hysterionica pinifolia Bioactiv. Compounds Polyacetylene Compounds (E)-undec-3-en-5 7-diyne-1-ol Insecticidal Activ.ty

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New insights into renal lipid dysmetabolism in diabetic kidney disease

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World Journal of Diabetes 2021年第5期12卷 524-540页

作者： Alla Mitrofanov. George Burke sandra Merscher Alessia Fornoni Peggy and Harold Katz Family Drug Discov.ry Center University of MiamiMiller School of MedicineMiamiFL 33136United States Katz Family Div.sion of Nephrology and Hypertension Department of MedicineUniversity of MiamiMiller School of MedicineMiamiFL 33136United States Department of Surgery University of MiamiMiller School of MedicineMiamiFL 33136United States Diabetes Research Institute University of MiamiMiller School of MedicineMiamiFL 33136United States

Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in v.rious tissues and organs,including the *** suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically activ. sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the dev.lopment of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactiv. oxygen species production,oxidativ. stress,inflammation,or cell ***,control of renal lipid dysmetabolism is a v.ry important therapeutic goal,which needs to be *** article will rev.ew some of the recent adv.nces leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.

关键词： Diabetes Lipids Free fatty acids ATP-binding cassette transporters sub-class A Sterol-O-acyltransferase 1 CD36 Sphingolipids Sphingomyelin phosphodiesterase acid-like 3b Diabetic kidney disease

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