BACKGROUND AND OBJECTIVES

Acute kidney injury (AKI) is a common complication of critical illness that often leads to increased mortality and morbidity. Biomarkers detect AKI earlier, providing a window of opportunity for timely intervention. Of the recent biomarkers in literature, the cell cycle arrest biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) were found to be superior in predicting AKI. Our study aimed to evaluate the diagnostic performance of urine TIMP-2/IGFBP-7 in its ability to predict AKI and major adverse kidney events within 30 days (MAKE30) among high-risk patients for AKI. MAKE30 is a composite outcome comprised of all-cause mortality, use of renal replacement therapy (RRT), or persistent renal dysfunction at hospital discharge truncated at 30 days.

METHODS

We conducted a prospective, cross-sectional study which included 135 adult, non-COVID ICU patients. Baseline urine TIMP-2/IGFBP-7 results were used to dichotomize the population into low risk (< 0.3 ng/mL) or high risk (≥ 0.3 ng/mL) for AKI. Participants were then observed for 30 days and monitored for MAKE30 outcomes. ROC curves were created to calculate the sensitivity, specificity, NPV, PPV, and the AUC of the 0.3 ng/mL cut-off to predict the AKI and MAKE30.

RESULTS

Urine TIMP-2/IGFBP-7 cutoff of 0.3 ng/mL predicted AKI with a sensitivity of 82.4%, specificity of 79.2%, PPV of 57.1%, NPV of 93% and AUC of 0.81. MAKE30 was detected with a sensitivity of 62.8%, specificity of 76.1%, PPV of 55.1%, NPV of 81.4% and AUC of 0.69. Elevated levels of urine TIMP-2/IGFBP-7 were found to be associated with AKI (p <0.01), MAKE30 (p <0.01) and all of its subcomponents. Survival or discharge after 30 days were found to be associated with lower urine TIMP-2/IGFBP-7 levels (p <0.01).

CONCLUSION

Urine TIMP-2/IGFBP-7, at its current cutoff at 0.3 ng/mL, can predict the likelihood of developing AKI and major adverse kidney events among high-risk patients for AKI. It can serve as a useful adjunct to existing methods, such as serum creatinine, in the early diagnosis and prognosis of acute kidney injury and expanding the therapeutic window to prevent disease progression and improve outcomes.

Acute Kidney Injury ; Biomarkers ; Urine ; Tissue Inhibitor Of Metalloproteinase-2 ; Insulin-like Growth Factor Binding Proteins

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
Child ; Female ; Humans ; Pregnancy ; Body Height ; Human Growth Hormone/therapeutic use* ; Hyperplasia ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Prospective Studies ; Pituitary Gland/pathology* ; Recombinant Proteins/therapeutic use*

OBJECTIVE: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo. METHODS: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 μmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms. RESULTS: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 μmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 μmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 μmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively. CONCLUSION BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.
Animals ; Candida albicans ; drug effects ; metabolism ; pathogenicity ; physiology ; Candidiasis, Vulvovaginal ; drug therapy ; genetics ; immunology ; microbiology ; Chemokine CCL2 ; genetics ; immunology ; Disease Models, Animal ; Fatty Acids, Monounsaturated ; administration & dosage ; Female ; Fungal Proteins ; genetics ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; immunology ; Mice ; Virulence ; drug effects ; Virulence Factors ; genetics ; metabolism

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.
Alkaline Phosphatase ; Alopecia ; Cell Survival ; Coculture Techniques ; Fetal Blood* ; Hair Follicle ; Hair* ; Humans* ; In Vitro Techniques ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins* ; Mesenchymal Stromal Cells ; Regeneration ; Stem Cells* ; Umbilical Cord* ; Vascular Endothelial Growth Factor A

OBJECTIVES: The insulin-like growth factor binding proteins (IGFBP) regulate the bioavailability and bioactivity of insulin-like growth factor. We aimed to evaluate whether the IGFBP-3 level undergo major changes during perioperative periods according to the different kind of anesthetic agents. METHODS: Eighteen adults scheduled for elective total abdominal hysterectomy were enrolled. The patients were randomly assigned to have either propofol or isoflurane for maintenance of general anesthesia. A venous sample was taken for analysis of IGFBP-3 at the following time points: before induction, at the time of peritoneal closure, 1 hour after extubation at recovery room, and 2 and 5 postoperative days. The samples were analyzed by enzyme linked immunosolvent assay. RESULTS: Demographic data were similar between groups. In the both groups, the IGFBP-3 concentration decreased after anesthesia induction, reaching a nadir at the time of peritoneal closure without a significant difference between groups. In analysis between groups, the IGFBP-3 concentration in the isoflurane group on the postoperative 5th day was recovered to preoperative value and significantly higher than that in the propofol group (P < 0.05). CONCLUSION: This is the first study to show that the anesthetics used for general anesthesia affect the IGFBP-3 level during perioperative periods. The decrease of IGFBP-3 level following anesthesia induction in the isoflurane group was recovered to preoperative value, whereas that observed in the propofol group was not recovered on the postoperative 5th day. Further study is needed to establish the definitive effect of general anesthetics on IGFBP-3 and provide a comprehensive interpretation.
Adult ; Anesthesia ; Anesthesia, General ; Anesthetics ; Anesthetics, General ; Biological Availability ; Humans ; Hysterectomy ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Isoflurane ; Perioperative Period ; Propofol ; Recovery Room

Insulin-like growth factor binding proteins (IGFBPs) are major regulators of insulin-like growth factor bioavailability and activity in metabolic signaling. Seven IGFBP family isoforms have been identified. Recent studies have shown that IGFBPs play a pivotal role in metabolic signaling and disease, including the pathogenesis of obesity, diabetes, and cancer. Although many studies have documented the various roles played by IGFBPs, transcriptional regulation of IGFBPs is not well understood. In this review, we focus on the regulatory mechanisms of IGFBP gene expression, and we summarize the findings of transcription factor activity in the IGFBP promoter region.
Biological Availability ; Gene Expression ; Humans ; Insulin-Like Growth Factor Binding Protein 2* ; Insulin-Like Growth Factor Binding Proteins ; Liver ; Metabolic Diseases ; Obesity ; Promoter Regions, Genetic ; Protein Isoforms ; Transcription Factors

OBJECTIVETo investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA).

METHODSA total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups.

RESULTSΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function.

CONCLUSIONSrhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.

Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Infant, Small for Gestational Age ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use

Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.
Axis* ; Carrier Proteins ; Diabetes Mellitus* ; Diabetes Mellitus, Type 1 ; Glucose ; Glucose Intolerance ; Humans ; Insulin ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Lipid Metabolism

A disintegrin-metalloproteinase 28 (ADAM28) is one of important members of ADAM family, that is involved in various biological events including cell adhesion, proteolysis, growth and metastasis of solid tumors and hematological malignancies. Studies have shown that ADAM28 is highly expressed in several human tumors, such as lung, breast and bladder cancers, and chronic lymphocytic leukemia, and its tissue expression levels correlate with cancer metastasis. ADAM28-mediated cancer cell metastasis may be related with the cleavage of von Willebrand's factor (vWF), insulin-like growth factor binding protein-3 (IGFBP-3) and connective tissue growth factor (CTGF), as well as the promoting PSGL-1/P-selectin-mediated cell adhesion. This review summarizes the basic and translational aspects of ADAM28 biology that might stimulate the interest in ADAM28 research and discovery of novel ADAM28 targets, providing potential novel therapies for metastatic cancers.
ADAM Proteins ; metabolism ; Cell Adhesion ; Connective Tissue Growth Factor ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; metabolism ; Neoplasm Metastasis ; Neoplasms ; pathology ; von Willebrand Factor ; metabolism

Bone Regeneration ; Bone and Bones ; Humans ; Insulin-Like Growth Factor Binding Proteins