2025
Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses
Lakshmipathi J, Santha S, Li M, Qian Y, Roy S, Luheshi N, Politi K, Bosenberg M, Eyles J, Muthusamy V. Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses. Cancer Immunology, Immunotherapy 2025, 74: 250. PMID: 40560386, PMCID: PMC12198101, DOI: 10.1007/s00262-025-04105-0.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseTumor-associated macrophagesCytotoxic T cellsImmune responseActivity of checkpoint inhibitorsAnti-PD-L1 antibodyPhagocytosis of tumor cellsAnti-PD-L1Enhanced anti-tumorAntigen presentation machineryCell-based immune responsesMurine tumor modelsTh1-type cytokinesColorectal carcinoma tumorsICI resistanceMurine IL12Checkpoint inhibitorsPresentation machineryIntratumoral deliveryResistant tumorsAdvanced diseaseCarcinoma tumorsTumor microenvironmentMurine tumorsT cellsA genetic modifier links integrin α5 to the phenotypic variation in fibronectin 1a mutant zebrafish.
Capon S, Maroufidou A, Feltes M, Xu Y, Matharoo D, Jülich D, Holley S, Farber S, Stainier D. A genetic modifier links integrin α5 to the phenotypic variation in fibronectin 1a mutant zebrafish. PLOS Genetics 2025, 21: e1011747. PMID: 40549824, PMCID: PMC12212883, DOI: 10.1371/journal.pgen.1011747.Peer-Reviewed Original ResearchConceptsMutant phenotypePhenotypic variationNonsense mutationGenetic modifiersDouble mutant analysisWhole-genome sequencingITGA5 expressionSevere phenotypeIntegrin alpha 5Mutant analysisMutant larvaeProximal promoterMutantsMutant zebrafishCardia bifidaGene expressionIntegrin A5Genetic backgroundAlpha 5PhenotypeMutationsExpression levelsFibronectinFunctional cardiovascular systemZebrafishA minimum data standard for wildlife disease research and surveillance
Schwantes C, Sánchez C, Stevens T, Zimmerman R, Albery G, Becker D, Brookson C, Kading R, Keiser C, Khandelwal S, Kramer-Schadt S, Krut-Landau R, McKee C, Montecino-Latorre D, O’Donoghue Z, Olson S, O’Shea M, Poisot T, Robertson H, Ryan S, Seifert S, Simons D, Vicente-Santos A, Wood C, Graeden E, Carlson C. A minimum data standard for wildlife disease research and surveillance. Scientific Data 2025, 12: 1054. PMID: 40544158, PMCID: PMC12182584, DOI: 10.1038/s41597-025-05332-x.Peer-Reviewed Original ResearchUpdate of the sideroflexin (SLC56) gene family
Katsafadou A, Nebert D, Krupenko S, Thompson D, Vasiliou V. Update of the sideroflexin (SLC56) gene family. Human Genomics 2025, 19: 69. PMID: 40542427, PMCID: PMC12180156, DOI: 10.1186/s40246-025-00779-w.Peer-Reviewed Original ResearchConceptsIron-sulfur cluster assemblyMitochondrial iron-regulatedMitochondrial iron homeostasisMitochondrial serine transporterMitochondrial transmembrane proteinOxidative phosphorylation disordersSolute carrier familyEukaryotic speciesOne-carbon metabolismMitochondrial researchGene familyModel organismsCellular homeostasisEvolutionary trajectoriesMitochondrial metabolismTransmembrane domainCongenital sideroblastic anemiaTransmembrane proteinsCarrier familySideroflexinHeme biosynthesisIron regulationCitrate metabolismMitochondrial functionSerine transportATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection
Liang C, Zhai T, Chen J, Fang S, Zhu Y, Liu L, Yu N, Zhao H. ATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2421995122. PMID: 40540593, PMCID: PMC12207453, DOI: 10.1073/pnas.2421995122.Peer-Reviewed Original ResearchConceptsCochlear efferent systemHearing sensitivityATP-gated P2X7 receptorP2X7 receptorOuter hair cellsAuditory nerveInnervate outer hair cellsEfferent systemAuditory brainstem responseSpiral ganglion (SGActive cochlear amplificationActive cochlear mechanicsEfferent nervesP2X7 KO miceIncreased susceptibility to noiseSusceptibility to noiseNeuronal functionAcoustic startle responseHair cellsBrainstem responseHearing lossEfferent suppressionHearing disordersOHC electromotilityNoise exposureSpermidine is a key polyamine required by intracellular parasites for survival within host erythrocytes
Singh P, Choi J, Cornillot E, Mamoun C. Spermidine is a key polyamine required by intracellular parasites for survival within host erythrocytes. Science Advances 2025, 11: eadv2397. PMID: 40531988, PMCID: PMC12175890, DOI: 10.1126/sciadv.adv2397.Peer-Reviewed Original ResearchConceptsSpermidine biosynthesisIntracellular parasitesRegulate protein translationOxidative stress defenseDe novo synthesisProduction of reactive oxygen speciesTranslational regulationIncreased production of reactive oxygen speciesMolecular functionsProtein translationStress defensePlasmodium falciparum</i>Evolutionary adaptationReactive oxygen speciesAgent of human babesiosisIntraerythrocytic developmentBiosynthesisOxygen speciesHost erythrocytesTherapeutic targetProtein–Protein Interactions in Base Excision Repair
Rathnaiah G, Sweasy J. Protein–Protein Interactions in Base Excision Repair. Biomolecules 2025, 15: 890. PMID: 40563529, PMCID: PMC12190888, DOI: 10.3390/biom15060890.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsBase excision repairPolynucleotide kinase-phosphataseApurinic/apyrimidinic endonuclease 1X-ray repair cross-complementing protein 1Single-nucleotide base excision repairBase excision repair componentsExcision repairDNA polymerase BBase excision repair pathwayRepair of damaged basesDNA repair processesCore enzymePolymerase BDNA intermediatesProtein-proteinDamaged basesSingle-nucleotideDNA glycosylaseMolecular networksMolecular underpinningsDNAFunctional evidenceProtein 1EnzymeVisceral pain-related acute actions of cerulein on mouse and human sensory neurons.
Goyal S, Zurek N, Ehsanian R, Goyal S, Jones D, Shilling M, Desir G, Gorelick F, Westlund K, Alles S. Visceral pain-related acute actions of cerulein on mouse and human sensory neurons. Molecular Pain 2025, 21: 17448069251353346. PMID: 40524328, DOI: 10.1177/17448069251353346.Peer-Reviewed Original ResearchConceptsDorsal root gangliaDRG neuronsPain behaviorCCK-AAcute pancreatitisHuman DRGWhole-cell patch-clamp electrophysiologyIncreased excitabilityHuman dorsal root gangliaDorsal root ganglia neuronsHuman sensory neuronsThoracic DRG neuronsVon Frey testAssess pain behaviorCCK-A receptorsInduce acute pancreatitisPatch-clamp electrophysiologyCCK-B receptorsPre-clinical studiesResponse to ceruleinComplaints of patientsAntagonist of cholecystokininMechanical hypersensitivityPancreatic painCholecystokinin systemsRole of PLK4 inhibition in cancer therapy
Banik K, Hayman T. Role of PLK4 inhibition in cancer therapy. Cancer And Metastasis Reviews 2025, 44: 55. PMID: 40512236, DOI: 10.1007/s10555-025-10271-5.Peer-Reviewed Original ResearchConceptsAssociated with more advanced diseaseCancer therapyAssociated with tumor progressionMore advanced diseasePolo-like kinase 4PLK4 overexpressionMultiple cancer typesAdvanced diseaseTherapeutic resistanceClinical outcomesTumor progressionSmall molecule inhibitorsHuman tumorsCancer typesDNA-damaging agentsSerine-threonine kinaseCancerOncogenic processesTherapeutic gainTherapeutic targetPolo-like kinase 4 inhibitorPLK4 inhibitionKinase 4Genomic instabilityTherapyEndothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis
Zhang T, Huang X, Goodwin J, Wen R, Liu Y, Yang Y, Zhang T, Zheng Y, Chen A, Hao P, Tong X, Yang N, Liu C. Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis. Science Advances 2025, 11: eadt7589. PMID: 40498836, PMCID: PMC12154197, DOI: 10.1126/sciadv.adt7589.Peer-Reviewed Original ResearchConceptsVascular leakagePuncture (CLP)-induced polymicrobial sepsisRegulating endothelial barrier functionCLP-challenged miceEndothelial barrier dysfunctionTrans-endothelial electrical resistanceEndothelial barrier functionLipopolysaccharide (LPS)-induced endotoxemiaVascular endothelial cellsPattern recognition receptorsSurvival benefitMultiorgan failurePolymicrobial sepsisTrans-endothelial migrationCecal ligationBacterial pneumoniaLung injuryBarrier dysfunctionVascular injurySingle-cell RNA sequencingDecreased mortalityInflammatory stormBacterial infectionsHeterogeneity of vascular endothelial cellsSepsisSystemic in utero gene editing as a treatment for cystic fibrosis
Ricciardi A, Barone C, Putman R, Quijano E, Gupta A, Nguyen R, Mandl H, Piotrowski-Daspit A, Lopez-Giraldez F, Luks V, Freedman-Weiss M, Farrelly J, Ahle S, Lynn A, Glazer P, Saltzman W, Stitelman D, Egan M. Systemic in utero gene editing as a treatment for cystic fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2418731122. PMID: 40493185, PMCID: PMC12184489, DOI: 10.1073/pnas.2418731122.Peer-Reviewed Original ResearchConceptsUtero gene editingCystic fibrosisCF transmembrane conductance regulatorTreat CF patientsTransmembrane conductance regulatorWild-type miceIrreversible organ damageNormal organ developmentTreat monogenic diseasesCFTR activityCF patientsConductance regulatorDisease-causing genesMultiorgan diseaseDisease improvementOrgan damageGene editingMonogenic diseasesMutation correctionPolymeric nanoparticlesGastrointestinal tissuesDiseaseBirthFibrosisReproductive systemNeuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer
Delanne-Cuménal M, Defaye M, Delanne-Cuménal A, Ahmed M, Ho V, Abdullah N, Alhassoun M, Svendsen K, Mager L, Schlessinger J, Hirota S, Altier C. Neuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2500632122. PMID: 40493183, PMCID: PMC12184428, DOI: 10.1073/pnas.2500632122.Peer-Reviewed Original ResearchConceptsColitis-associated colorectal cancerAnaplastic lymphoma kinaseColorectal cancerAnaplastic lymphoma kinase activityColitis-associated colorectal cancer progressionAnaplastic lymphoma kinase receptorTRPV1+ nociceptorsDevelopment of colitis-associated colorectal cancerMouse colonic organoidsALK signalingInflammatory painTumor burdenTreatment resistanceSensory neuronsTumor growthColonic organoidsALKAL2Colonic mucosaOverall inflammationCancer progressionCancerIn vivoTRPV1NeuronsInflammationRedundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation
Baro M, Lee H, Kelley V, Lou R, Phoomak C, Politi K, Zeiss C, Van Zandt M, Contessa J. Redundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation. Cell Chemical Biology 2025, 32: 839-853.e6. PMID: 40494352, DOI: 10.1016/j.chembiol.2025.05.005.Peer-Reviewed Original ResearchConceptsN-glycosylationTrafficking of cell surface receptorsInhibits N-glycosylationCell surface receptorsGlycan synthesisCatalytic subunitOligosaccharyltransferaseEnzymatic activitySurface receptorsSTT3BSTT3ACharacterized in vitroDownstream effectsLung cancer xenograftsTherapeutic targetPatient-derivedBiological activityTumor regressionCancer xenograftsSmall moleculesGrowth delayTherapeutic agentsGlycansCurrent cutting-edge omics techniques on musculoskeletal tissues and diseases
Li X, Fang L, Zhou R, Yao L, Clayton S, Muscat S, Kamm D, Wang C, Liu C, Qin L, Tower R, Karner C, Guilak F, Tang S, Loiselle A, Meyer G, Shen J. Current cutting-edge omics techniques on musculoskeletal tissues and diseases. Bone Research 2025, 13: 59. PMID: 40484858, PMCID: PMC12146411, DOI: 10.1038/s41413-025-00442-z.Peer-Reviewed Original ResearchConceptsDisease-associated alterationsImpact quality of lifeIntervertebral disc degenerationMusculoskeletal tissuesMolecular landscapeDisc degenerationQuality of lifeBone fracturesRheumatoid arthritisBulk transcriptomesTherapeutic targetTissue microenvironmentClinical applicationPathophysiological processesDisease mechanismsEconomic burdenMusculoskeletal disordersImpact qualityOmics technologiesMulti-omics integrationDiseaseSingle-cellTissueSpatial organization of cellsCellular heterogeneityHeterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13: rp103620. PMID: 40488445, PMCID: PMC12148328, DOI: 10.7554/elife.103620.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentSchizophreniaImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorDesign and Evaluation of Novel Ginger 6‑Shogaol-Inspired Phospholipase C Inhibitors to Enhance β‑Agonist-Induced Relaxation in Human Airway Smooth Muscle
Luković E, Zhu Y, Zhang Y, Genualdi J, Sang S, Emala C. Design and Evaluation of Novel Ginger 6‑Shogaol-Inspired Phospholipase C Inhibitors to Enhance β‑Agonist-Induced Relaxation in Human Airway Smooth Muscle. Journal Of Medicinal Chemistry 2025, 68: 12626-12640. PMID: 40489244, DOI: 10.1021/acs.jmedchem.5c00378.Peer-Reviewed Original ResearchConceptsStructure-activity analysisHuman airway smooth muscleHuman airway smooth muscle cellsPhenol moietyAirway smooth muscle cellsHuman tracheal tissueHydroxyl groupsAirway smooth musclePhospholipase C inhibitorSmooth muscle cellsMouse lung tissuePoor symptom controlDerivativesIntracellular calciumSmooth muscleMuscle cellsAsthma treatmentLung tissueC inhibitorTherapeutic potentialNovel therapeuticsTracheal tissueEnhanced inhibitionSymptom controlInositol phosphatesFTO inhibition enhances the therapeutic index of radiation therapy in head and neck cancer
Ji L, Pu L, Wang J, Cao H, Melemenidis S, Sinha S, Guan L, Laseinde E, von Eyben R, Richter S, Nam J, Kong C, Casey K, Graves E, Frock R, Le Q, Rankin E. FTO inhibition enhances the therapeutic index of radiation therapy in head and neck cancer. JCI Insight 2025, 10: e184968. PMID: 40485587, DOI: 10.1172/jci.insight.184968.Peer-Reviewed Original ResearchConceptsTherapeutic index of radiation therapyHPV- head and neck squamous cell carcinomaRadiation therapyTherapeutic indexRT responseHead and neck squamous cell carcinomaRadiation-induced oral mucositisNeck squamous cell carcinomaPharmacological inhibitionHead and neck cancerDrug-radiotherapy combinationsOverall survival rateEfficacy of RTSquamous cell carcinomaTherapeutic targetObesity-related genesAssociated with increased DNA damageChemoradiation treatmentOral mucositisCell carcinomaHNSCC treatmentHNSCC cellsNeck cancerPotential therapeutic targetCancer therapeutic targetGlucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson’s disease
Lee S, Yin L, Xiao N, Rhee T, Lo H, Wong S, Fox S, Teopiz K, Lam B, Zheng Y, Le G, Mansur R, Rosenblat J, McIntyre R. Glucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson’s disease. CNS Spectrums 2025, 30: e44. PMID: 40485141, DOI: 10.1017/s109285292510031x.Peer-Reviewed Original ResearchConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsGLP-1RAsCentral nervous systemReceptor agonistsEvidence of clinically meaningful benefitFood and Drug Administration (FDA)-approved treatmentsTreatment-emergent adverse eventsParkinson's diseaseEffects of GLP-1RAsEmergent adverse eventsClinically meaningful benefitFDA-approved treatmentClinical trial evidenceNo current therapyTreatment of Parkinson's diseasePreclinical evidenceAdverse eventsCurrent therapiesMeaningful benefitClinical evidenceFeatures of PDTherapeutic benefitTrial evidenceInsulin resistanceSeparation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1
Smoom R, May C, Lichtental D, Bar-Ness K, Rangel R, Khoury J, Nachmani D, Avrahami D, Ahangari F, Skordalakes E, Kaminski N, Kaestner K, Tzfati Y. Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1. Nucleic Acids Research 2025, 53: gkaf507. PMID: 40530700, PMCID: PMC12203905, DOI: 10.1093/nar/gkaf507.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsDisease Models, AnimalDNA DamageDNA HelicasesDyskeratosis CongenitaFetal Growth RetardationGrowth DisordersHematopoiesisHumansIntellectual DisabilityLimb Deformities, CongenitalLungMiceMicrocephalyPoint MutationTelomereTelomere HomeostasisX-Linked Intellectual DisabilityConceptsHoyeraal-Hreidarsson syndromeTelomere protectionLength regulationTelomere length regulationTelomere-related diseasesTelomere biology disordersDNA helicaseMouse genomeGenome stabilityMouse modelMouse telomeresAberrant hematopoiesisGenomic instabilityPoint mutationsHouse miceTelomeric DNA damageAnaphase bridgesRTEL1Amino acidsTelomereMechanistic rolesDNA damageMutationsIsoleucine mutationGenomeDevelopment of Mouse Models for Ménétrier's Disease.
Gabriel T, Park J, Madala S, Coffey R, Huh W. Development of Mouse Models for Ménétrier's Disease. Journal Of Visualized Experiments 2025 PMID: 40549725, DOI: 10.3791/67981.Peer-Reviewed Original ResearchConceptsSpasmolytic polypeptide-expressing metaplasiaLoss of parietal cellsMouse modelFeatures of MDMouse linesFoveolar hyperplasiaParietal cellsEGF receptorTransforming growth factor-aEGFR-neutralizing antibodyChief cellsDevelopment of mouse modelsChief cell differentiationDecreased acid secretionGiant rugal foldsTransgenic mouse linesInducible mouse modelGrowth factor AModel of MDIn vivo modelsMist1 expressionHistological remissionClinical improvementHistopathological featuresTreatment options
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