OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

BACKGROUND: Heavy metals are significant risk factors for kidney function. Numerous studies have shown that exposure to heavy metals negatively correlates with kidney function through oxidative stress pathways, and serum α-klotho is linked to oxidative stress. However, the role of α-klotho in the relationship between blood lead, mercury, and kidney function remains unclear. METHOD: This study evaluated the mediating role of alpha-klotho in the relationship between lead, mercury and renal function, using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) in U.S. adults aged 40-79. The sample included 11,032 participants, with blood lead, mercury, α-klotho, and other relevant covariates measured. Inductively coupled plasma mass spectrometry was used to assess blood lead and mercury levels, and enzyme-linked immunosorbent assay (ELISA) was employed to measure serum α-klotho. Kidney function was evaluated using estimated glomerular filtration rate (eGFR) based on creatinine levels. Multivariable linear regression was conducted to analyze the relationships between blood lead, mercury, α-klotho, and eGFR. A mediation analysis model was used to assess whether α-klotho influenced these associations. RESULTS: We observed a significant association between blood lead and eGFR. Mediation analysis revealed that α-klotho accounted for 12.76% of the relationship between serum lead and eGFR in the NHANES population. Subgroup analysis showed that α-klotho mediated 12.43%, 6.87%, 21.50% and 5.44% of the relationship between blood lead and eGFR in women, middle-aged adults (40-59 years old), without cardiovascular disease and hypertension, respectively. However, α-klotho did not mediate the relationship between blood mercury and eGFR in terms of gender or age. This newly identified pathway may provide valuable insights for the prevention and treatment mechanisms related to kidney function impairment. CONCLUSION We found that blood lead was associated with renal function. According to the results of subgroup analysis, for blood lead, serum α-klotho mediated the association in females, middle aged 60-79 years. The relationship between blood mercury and renal function was not clinically significant, and serum α-Klotho mediated the relationship between blood mercury and renal function without significant clinical significance.
Humans ; Middle Aged ; Lead/blood* ; Female ; Klotho Proteins ; Male ; Aged ; Adult ; Mercury/blood* ; Glomerular Filtration Rate ; Nutrition Surveys ; United States ; Kidney/physiology* ; Glucuronidase/blood* ; Environmental Pollutants/blood*

OBJECTIVE: To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome. METHODS: Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (=35) and treatment group (=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers. RESULTS: Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group ( < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment ( < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks ( < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group ( < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group ( < 0.05) but only at 12 weeks in the control group ( < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects ( < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group ( < 0.05) but remained unchanged in the control group (>0.05), showing significant differences between the two groups. CONCLUSIONS Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.
Calcium ; blood ; Chronic Kidney Disease-Mineral and Bone Disorder ; blood ; therapy ; Drugs, Chinese Herbal ; pharmacology ; Enema ; Fibroblast Growth Factors ; blood ; Glucuronidase ; blood ; Humans ; Parathyroid Hormone ; blood ; Phosphorus ; blood ; Receptors, Fibroblast Growth Factor ; blood ; Renal Insufficiency, Chronic ; blood ; therapy ; Sweating Sickness ; blood ; therapy ; Syndrome

OBJECTIVETo explore the incidence of various types of mucopolysaccharidosis (MPS) and their clinical characteristics.

METHODSA total of 75 children highly suspected as having MPS underwent quantitative and electrophoretic analysis of urinary glycosaminoglycans (GAGs) and enzymatic analysis of seven types of MPS from January 2009 to December 2011. Fluorescence assay was used to measure the activities of α-L-iduronidase, iduronate-2-sulfatase, α-N-acetylglucosaminidase, galactosamine-6-sulfatase, β-galactosidase, arylsulfatase B and β-glucuronidase in the white blood cells.

RESULTSA total of 52 cases were confirmed with MPS based on clinical, radiological, and enzymatic examinations. The 52 cases, with a mean age of 4.0 ± 2.2 years, included 5 cases of MPS I (10%), 20 cases of MPS II (38%), 20 cases of MPS IVA (38%), 6 cases of MPS VI (12%) and 1 case of MPS VII (2%). No MPS IV B cases or MPS IIIB cases were found. Compared with healthy children of the same age, the GAG/Cr ratio was significantly elevated in 50 confirmed cases of MPS (two MPS IVA cases having no increased ratio). All children with increased urinary GAGs had a confirmed diagnosis of MPS. The age of onset was between 1 and 2 years after birth in most cases, and often complicated by hernia and valvular heart disease. Children with MPS I, MPS II, and MPS VI presented with ugly and unsmooth face, short stature, joint stiffness, and limitation of motion, while children with MPS IVA presented with short stature, skeletal dysplasia, and joint laxity.

CONCLUSIONSType IVA and type II are the most common in MPS cases, followed by type VI and type I. MPS children are characterized by special appearances including ugly and unsmooth facial appearance, short stature and skeletal dysplasia. Quantitative analysis of urinary GAG, as a simple, rapid, and reliable method, is recommended for screening of MPS.

Acetylglucosaminidase ; blood ; Child ; Child, Preschool ; Creatinine ; urine ; Female ; Glucuronidase ; blood ; Glycosaminoglycans ; urine ; Humans ; Iduronidase ; blood ; Infant ; Magnetic Resonance Imaging ; Male ; Mucopolysaccharidoses ; diagnosis ; enzymology ; pathology ; beta-Galactosidase ; blood

OBJECTIVETo assess the effect of Klotho gene transduction on the progression of hypertension and heart damage in spontaneous hypertensive rats (SHRs).

METHODSAn adeno-associated virus (AAV) carrying full-length mouse Klotho cDNA (rAAV.mKL) was constructed for in vivo expression of Klotho. Three different groups of male SHRs and a control group of sex and age-matched Sprague Dawley (SD) rats (5 rats per group) were used. The experimental groups of SHRs received an IV injection of phosphate buffered saline (PBS), rAAV.mKL and rAAV.EGFP, respectively. The control group only received equal-volume of PBS. The whole study has spanned 12 weeks. Plasma levels of insulin-like growth factor-1 (IGF-1) and insulin were measured with ELISA. The weight of whole heart was measured to calculate the heart weight index (HWI). EGFP expression of heart frozen sections was observed by fluorescence microscopy. Expression of mRNA and protein of Klotho, IGF-1, IGF-1 receptor (IGF-1R) and p-Akt were determined with RT-PCR, immunohistochemical analysis, and Western blotting. Hypertrophic myocardial cell and collagen fiber were observed by histological examination following Haematoxylin-Eosin and Masson staining.

RESULTSTransduction of rAAV.mKL can significantly prevent the increase of blood pressure in SHRs. Compared with the control group, the levels of Klotho mRNA and protein have both increased, and the plasma levels of IGF-1, insulin and glucose were elevated, whereas the expression of phosphor-Akt (also called Protein Kinase B, PKB) was decreased in the rAAV.mKL group. Furthermore, a decrease of hypertrophic myocardial cells and collagen fibers was noticed in the rAAV.mKL group compared with the control group.

CONCLUSIONThe Klotho gene can attenuate the progression of hypertension and abolishes myocardial hypertrophy and myocardial fibrosis. The protective effect observed in the rAAV.mKL group of SHRs may be attributed to increased Klotho protein and suppression of insulin and IGF-1 signaling pathways through inhibition of Akt phosphorylation.

Animals ; Blood Glucose ; Blood Pressure ; genetics ; Gene Expression ; Glucuronidase ; genetics ; metabolism ; Hypertension ; genetics ; metabolism ; pathology ; Insulin ; blood ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Myocardium ; metabolism ; pathology ; ultrastructure ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Transduction, Genetic

OBJECTIVETo evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice.

METHODSThe mice were divided into four experimental groups. Group I served as control; mice in group II were injected with monosodium urate crystal; group III consisted of monosodium urate crystal-induced mice who were treated with boswellic acid (30 mg/kg/b.w.); group IV comprised monosodium urate crystal-induced mice who were treated with indomethacin (3 mg/kg/b.w.). Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-α were determined in control and monosodium urate crystal-induced mice. In addition, the levels of β-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro.

RESULTSThe activities of lysosomal enzymes, lipid peroxidation, and tumour necrosis factor-α levels and paw volume were increased significantly in monosodium urate crystal-induced mice, whereas the activities of antioxidant status were in turn decreased. However, these changes were modulated to near normal levels upon boswellic acid administration. In vitro, boswellic acid reduced the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells.

CONCLUSIONSThe results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid, which was already well established by several investigators.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Antioxidants ; therapeutic use ; Arthritis, Gouty ; chemically induced ; drug therapy ; Female ; Glucuronidase ; metabolism ; Hydrolases ; metabolism ; Indomethacin ; therapeutic use ; Inflammation ; chemically induced ; drug therapy ; L-Lactate Dehydrogenase ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Neutrophils ; enzymology ; immunology ; Triterpenes ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood ; Uric Acid

OBJECTIVE: To observe the expression of HPA, bFGF and VEGF in nasopharyngeal angiofibroma, and then explore its significance of inducing angiogenesis in the tumor's expansibility growth. METHOD: The expression of heparanase, bFGF, VEGF and CD105 were examined in 30 (I - II period 9 cases, III - IV period 21 cases) samples from nasopharyngeal angiofibroma and 20 inferior turbinate tissues by immunohistochemical staining technique. The microvascular density (MVD) were measured by the immunohistostaining of CD105. The MVD was analyzed with the clinical stage. RESULT: The positive rates of the HPA, bFGF and VEGF expression in JNA tissues were significantly higher than that in inferior turbinate group (P < 0.05). The positive rates of HPA, bFGF and VEGF expression in III - IV period were obviously higher than that in I - II period (P < 0.05). The expression of bFGF and VEGF in JNA tissues was respectively positive correlated with the HPA (r = by 0.499, 0.582, P < 0.05); In JNA tissues, the mean MVD in both HPA and bFGF positive group was higher than each one single positive group or both negative express group (P < 0.05). And the mean MVD in both HPA and VEGF positive group was higher than each one single positive group or both negative express group (P < 0.05). CONCLUSION HPA can induce angiogenesis to promote tumor growth by releasing bFGF and VEGF. Targeting the HPA can be a new direction in JNA adjuvant treatment.
Adolescent ; Adult ; Angiofibroma ; blood supply ; pathology ; Angiogenesis Inducing Agents ; Child ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Glucuronidase ; metabolism ; Humans ; Male ; Nasopharyngeal Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo investigate the effects of silencing heparanase (HPA) on growth, angiogenesis and metastasis of human gastric carcinoma transplanted in nude mice.

METHODSHuman gastric carcinoma SGC-7901 cells and those cells with silenced HPA (gastric carcinoma SGC-7901-HPA(-)) were separately transplanted subcutaneously in 6 nude mice. The time, size and speed of tumor growth were recorded. RT-PCR and Western-blot were used to detect the expression of HPA mRNA and protein in the subcutaneous tumors of the two groups. Immunohistochemical staining was used to detect microvessel density (MVD) in the subcutaneous tumors of the two groups. Cells of the subcutaneous transplanted tumors of the two groups were separately injected into the peritoneal cavity of nude mice, 6 mice each. The growth of metastatic tumors in nude mice was observed.

RESULTSHuman gastric carcinoma SGC-7901 cells and SGC-7901-HPA(-) cells were subcutaneously inoculated in nude mice, and tumors appeared at 4 days and 7 days after inoculation, respectively. The MVD was (20.69 ± 1.20)/HP and (11.35 ± 1.94)/HP, respectively (P < 0.05). The expressions of HPA mRNA and protein of the subcutaneously transplanted SGC-7901-HPA(-) tumor were decreased. Four voluminous metastatic tumors caused by SGC-7901 cells occurred in 3 mice in the liver, right kidney, omentum and intestine. Two smaller abdominal metastatic tumors of SGC-7901-HPA(-) cells were found in the liver and right kidney.

CONCLUSIONSilencing HPA can inhibit the tumor growth, angiogenesis and metastasis of human gastric cancer in nude mice. It suggests that HPA might become a new target for prevention and treatment of gastric cancer.

Adenocarcinoma ; blood supply ; enzymology ; genetics ; pathology ; secondary ; Animals ; Cell Line, Tumor ; Gene Silencing ; Glucuronidase ; biosynthesis ; genetics ; physiology ; Humans ; Kidney Neoplasms ; secondary ; Liver Neoplasms ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Neoplasm Transplantation ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; blood supply ; enzymology ; genetics ; pathology

PURPOSE: Klotho mutant mice showed abnormal calcium and vitamin D metabolism, hyperphosphatemia and vascular calcification. We observed the frequencies of klotho gene polymorphism and investigated their relation with some clinical parameters including serum osteoprotegerin (OPG) levels in maintenance hemodialysis (HD) patients. METHODS: Total 88 patients (mean age 58+/-13 years, male:female=47:41) on maintenance HD were enrolled. The genotypings for G-395A in promoter and C1818T in exon 4 of klotho gene were performed with real-time polymerase chain reaction. We measured blood pressure, body mass index (BMI), and serum calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase, hs-CRP, lipid profiles and OPG. RESULTS: In G-395A in promoter, the distribution of genotypes was GG 66% (n=58), GA 23% (n=20) and AA 11% (n=10), respectively and the allele frequencies were 0.773 for G allele and 0.227 for A allele. In C1818T in exon 4, the distribution of genotypes was CC 63% (n=55), CT 30% (n=26), and TT 7% (n=7), and the frequencies were 0.773 for C allele and 0.227 for T allele. G-395A shows correlations with BMI and HDL-cholesterol (p<0.005). G-395A and C1818T in klotho gene show no statistical correlation with other clinical parameters of vascular calcification including OPG. CONCLUSION: Klotho G-395A and C1818T polymorphisms are not correlated with OPG in maintenance HD patients. Further research needs for the other klotho polymorphisms on chronic kidney disease and end-stage renal disease.
Alkaline Phosphatase ; Alleles ; Animals ; Blood Pressure ; Body Mass Index ; Calcium ; Exons ; Gene Frequency ; Genotype ; Glucuronidase ; Humans ; Hyperphosphatemia ; Mice ; Osteoprotegerin ; Parathyroid Hormone ; Phosphorus ; Real-Time Polymerase Chain Reaction ; Renal Dialysis ; Renal Insufficiency, Chronic ; Vascular Calcification ; Vitamin D

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Glucuronidase ; biosynthesis ; genetics ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; pathology