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Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

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Animal Models and Experimental Medicine 2023年第2期6卷 146-154页

作者： Yuhang Sun Bowen Guan Xing Liu Lingyan Zhang Xinpei Wang Aimin Meng Ran Gao National Human Diseases Animal Model Resource Center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)National Center of Technology Innovation for Animal ModelBeijingChina

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor *** susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of *** susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary ***:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in *** urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed *** for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase *** on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU ***:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC *** GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

关键词： angiotensin I converting enzyme busulfan hematopoietic stem cell injury inbred genetic diversity mice urinary marker

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Neutrophil gelatinase-associated lipocalin,kidney injury molecule-1,and periostin:Novel urinary biomarkers in diabetic nephropathy

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World Journal of Nephrology 2024年第4期13卷 117-124页

作者： Sakthivadivel Varatharajan Vishakha Jain Anand K Pyati Charan Neeradi Kotha Sugunakar Reddy Janardhana Reddy Pallavali Ilakkiya Priya Pandiyaraj Archana Gaur Department of General Medicine All India Institute of Medical Sciences-BibinagarHyderabad 508126TelanganaIndia Department of Biochemistry All India Institute of Medical Sciences-BibinagarHyderabad 508126TelanganaIndia Department of General Medicine Neelima Institute of Medical SciencesHyderabad 500088TelanganaIndia Department of Physiology All India Institute of Medical Sciences-BibinagarHyderabad 508126TelanganaIndia

BACKGROUND Globally,diabetic nephropathy(DN)is the primary cause of chronic kidney ***,renal function is monitored indirectly using measures of serum creatinine,estimated glomerular filtration rate(eGFR),and *** urinary biomarkers utilized in the early stages of DN have been described;these indicators can be used in the early identification of the disease,which is important for initiating treatment to halt or impediment the advance of diabetic *** To estimate neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and periostin(POSTN)levels as novel urinary biomarkers in *** In this hospital based cross-sectional study,a total of 160 patients of both genders aged 18 years or more;40 healthy participants and 120 patients with diabetes mellitus(DM)were *** with DM were divided into normoalbuminuria(n=40),microalbuminuria(n=40),and macroalbuminuria(n=40)groups as per urine albumin creatinine ratio(uACR).Blood urea,serum creatinine,uACR were *** NGAL,KIM-1,and POSTN were measured by enzyme linked immunosorbent *** eGFR was calculated and compared with urinary *** NGAL,KIM-1,and POSTN levels increased significantly in normo,micro,and macroalbuminuria with the highest in the macroalbuminuria *** creatinine ratio(ACR)showed a positive correlation with NGAL,KIM-1,and POSTN *** eGFR showed a weak negative correlation with ACR,NGAL,KIM-1,and *** was significantly lower in stage 1 compared to stage 2,3,and 4 kidney ***-1 was significantly decreased in stage 1 compared to stage 4 kidney *** was significantly decreased in stage 1 compared to stage 3 and 4 kidney *** receiver operator curve analysis of ACR,NGAL,KIM-1,and POSTN showed good sensitivity of 80%,75.8%,63.3%,and 80%respectively with a cut-off of 12.5 mg/g,4.5μg/L,1.5 ng/mL,and 37.5 ng/*** urinary NGAL and POSTN are independent markers of DN.

关键词： Diabetic nephropathy Neutrophil gelatinase-associated lipocalin Kidney injury molecule-1 Periostin urinary marker

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