Apelin-13 deficiency alters cortical bone geometry, organic bone matrix, and inhibits Wnt/ß-catenin signaling.

Adipokines play key roles in the regulation of obesity, type 2 diabetes mellitus, and bone growth. As a newly discovered hormone in the adipokines family, the precise role of Apelin-13 on bone metabolism is not yet clear. Apelin-13 and 25(OH)D3 expression were detected in freshly isolated serum of healthy individuals and osteoporosis patients with ELISA method. Apelin-13 deficient mice were set up and cortical bone geometry was measured with micro-computed tomography (Micro-CT) at 5 months old, then profile of organic bone matrix genes was detected with quantitative Real-Time PCR (qRT-PCR). Wnt/ß-catenin signaling molecules were assayed in primary osteocytes isolated from neonatal calvarias. Apelin-13 and 25(OH)D3 showed decreased expression in osteoporosis patients. Five-month-old Apelin deficient mice exhibited decreased total and bone marrow cavity area and periosteal and endocortical bone surface. Deficiency of Apelin-13 downregulated collagen maturation associated genes (loxl3 and loxl4) and Wnt/ß-catenin signaling, while loxl2 was upregulated, all of which indicated that Apelin-13 could play a role in regulating skeletal homeostasis. The decrease in bone formation in Apelin-13 deficient mice is associated with downregulation of organic bone matrix genes and Wnt/ß-catenin signaling molecules, all of these indicate that association of Apelin-13 with bone mineral density (BMD) could be mediated by Wnt/ß-catenin pathway.

Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for tuberculous meningitis.

RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.

Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, ß2 microglobulin, retinol binding protein and diabetic retinopathy.

BACKGROUND: Retinopathy is the most common microvascular disease of type 2 diabetes, and seriously threatens the life, health and quality of life of patients. It is worth noting that the development of diabetic retinopathy (DR) can be hidden, with few symptoms. Therefore, the preliminary screening of diabetic patients should identify DR as soon as possible, delay disease progression, and play a vital role in its diagnosis and treatment. AIM: To investigate the correlation between glycated hemoglobin A1c (HbA1c), urinary microalbumin (U-mALB), urinary creatinine (U-CR), mALB/U-CR ratio, ß2 microglobulin (ß2MG), retinol binding protein (RBP) and DR. METHODS: A total of 180 patients with type 2 diabetes mellitus attending the Second People's Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists. Based on whether they had combined retinopathy and its degree, 68 patients with diabetes mellitus without retinopathy (NDR) were assigned to the NDR group, 54 patients with non-proliferative DR (NPDR) to the NPDR group, and 58 patients with proliferative DR to the PDR group. General data, and HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR results were collected from the patients and compared among the groups. Pearson's correlation method was used to analyze the correlation between HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR indices, and multiple linear regression was applied to identify the risk factors for DR. Receiver operator characteristic (ROC) curves were also drawn. RESULTS: The differences in age, gender, systolic and diastolic blood pressure between the groups were not statistically significantly (P > 0.05), but the difference in disease duration was statistically significant (P < 0.05). The differences in fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglyceride between the groups were not statistically significant (P > 0.05). HbA1c in the PDR group was higher than that in the NPDR and NDR groups (P < 0.05). The levels of mALB, ß2MG, RBP, mALB/U-CR and U-CR in the PDR group were higher than those in the NPDR and NDR groups (P < 0.05). Multiple linear regression analysis showed that disease duration, HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR were risk factors for the development of DR. The ROC curve showed that the area under the curve (AUC) for the combination of indices (HbA1c + mALB + mALB/U-CR + U-CR + ß2MG + RBP) was 0.958, with a sensitivity of 94.83% and specificity of 96.72%, which was higher than the AUC for single index prediction (P < 0.05). CONCLUSION: HbA1c, mALB, mALB/U-CR, U-CR, ß2MG and RBP can reflect the development of DR and are risk factors affecting PDR, and the combination of these six indices has predictive value for PDR.

Association of [1H]-MRS quantified liver fat content with glucose metabolism status.

BACKGROUND: Previous literatures have implied that the liver fat deposition plays a crucial role in the development and progression of insulin resistance. In the present study, we aimed to investigate the association of liver fat content (LFC) with glucose metabolism status in the population of newly diagnosed type 2 diabetes mellitus (nT2DM), prediabetes mellitus (PDM) and normal controls (NC), and assessing if the LFC could as an indicator for the prediction of T2DM. METHODS: A total of 242 subjects (including 141 nT2DM patients, 48 PDM subjects and 53 NC) were enrolled. The levels of LFC were quantified by using the proton magnetic resonance spectroscopy ([1H]-MRS) technique. Clinical and laboratory parameters of study subjects were collected by medical records and biochemical detection. One-way ANOVA or nonparametric test (Kruskal-Wallis) was applied for intergroup comparisons; intergroup comparison was performed in using of Bonferroni multiple-significance-test correction. RESULTS: There were significantly increased LFC levels in nT2DM (14.72% ± 6.37%) than in PDM (9.62% ± 4.41%) and that of NC groups (5.11% ± 3.66%) (all p < 0.001). The prevalence of nonalcoholic fatty liver disease (NAFLD) was also found to be increased in nT2DM (91.48%) than in PDM (85.41%) and that of NC (32.07%) groups. Correlation analysis revealed that the increase of LFC positively associated with fast plasma glucose (FPG), 2 h plasma glucose (PG), Delta G30 and homeostatic model assessment of insulin resistance (HOMA-IR), negatively associated with Delta Ins30, Delta C30, Ins30/G30 AUC, CP30/G30 AUC, Ins AUC/G AUC, CP AUC/G AUC, homeostatic model assessment for ß-cell function index (HOMA-ß) and matsuda insulin sensitivity index (Matsuda ISI). Multilinear regression analysis showed that LFC, body mass index (BMI) and diastolic blood pressure (DBP) contributed for the prediction of HOMA-IR, and total cholesterol (TC), age, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) were the significant contributors for HOMA-ß. CONCLUSIONS: Our study revealed an increased LFC level and prevalence of NAFLD in nT2DM than in PDM and that of NC groups, the increase of LFC was closely associated with insulin resistance and impaired glucose metabolism status, may be regarded as potential indicator contributing to the development and progression of T2DM.

The neurovascular protective effect of alogliptin in murine MCAO model and brain endothelial cells.

Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.

Contrast-induced nephropathy in patients with diabetes mellitus between iso- and low-osmolar contrast media: A meta-analysis of full-text prospective, randomized controlled trials.

PURPOSE: This study was conducted to compare iso-osmolar contrast medium, iodixanol, with low-osmolar contrast media (LOCM) for assessing contrast-induced nephropathy (CIN) incidence, exclusively in the diabetic population. METHOD: A systematic search was conducted for full-text, prospective, randomized controlled trials (RCTs). The primary outcome was incidence of CIN. Medline, Cochrane Central Register of Controlled Trials, and other sources were searched until May 31, 2017. RESULTS: Twelve RCTs finally met the search criteria. Iodixanol did not significantly reduce the risk of CIN (risk ratio [RR]: 0.72, 95% confidence interval (CI): [0.49, 1.04], p = 0.08). However, there was significantly reduced risk of CIN when iodixanol was compared to a LOCM agent iohexol (RR: 0.32, 95% CI [0.12, 0.89]). There were no differences between iodixanol and the other non-iohexol LOCM (RR: 0.92, 95% CI [0.68, 1.25]). CONCLUSION: In diabetic populations, iodixanol is not associated with a significant reduction of CIN risk. Iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found.

CD9 modulates proliferation of human glioblastoma cells via epidermal growth factor receptor signaling.

The tetraspanin CD9 has previously been shown to be involved in various cellular activities, including proliferation and migration. In addition, CD9 has been shown to be associated with epidermal growth factor receptor (EGFR). A common characteristic of glioblastoma multiforme histology is EGFR amplification, which affects signal transduction processes. The anti-proliferative effects of CD9 have been linked to EGFR signaling pathways, including phosphorylation of phosphoinositide-3-kinase (PI3K)/Akt and activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (Erk). The present study demonstrated that CD9 decreased the phosphorylation of EGFR at specific sites. In addition, CD9 attenuated EGFR signaling of PI3K/Akt and MAPK/Erk, which was associated with cell growth and proliferation. Conversely, small hairpin RNA-mediated knockdown of CD9 expression enhanced the activation of EGFR signal transduction pathways, including PI3K/Akt and MAPK/Erk. These results suggested that the mechanism underlying CD9-induced suppression of cell proliferation may involve the inhibition of phosphorylation of EGFR and the activity of PI3K/Akt and MAPK/Erk signaling pathways.

[Distribution of Bt protein in transgenic cotton soils].

A pot experiment with red soil, yellow brown soil, and yellow cinnamon soil was conducted to detect the Bt protein content in rhizosphere and non-rhizosphere soils at different growth stages of transgenic Bt cotton and common cotton by using enzyme linked immunosorbent assay (ELISA). With the planting of transgenic Bt cotton, the Bt protein content in rhizosphere soil was significantly higher than that in non-rhizosphere soil; while in common cotton soils, there was no significant difference in the Bt protein content between rhizosphere soil and non-rhizosphere soil. At bud stage of transgenic Bt cotton, the Bt protein content in rhizosphere soil was in the order of yellow cinnamon soil > yellow brown soil > red soil, being 144% 121%, and 238% of that in common cotton rhizosphere soil; at florescence stage of transgenic Bt cotton, the Bt protein content in rhizosphere soil was in the order of yellow brown soil > yellow cinnamon soil > red soil, being 156% , 116% , and 197% of that in common cotton rhizosphere soil, respectively. Regardless of planting Bt cotton or common cotton, the Bt protein content in rhizosphere and non-rhizosphere soils had an initial increase with the growth of cotton, peaked at florescence stage, and then decreased. Throughout the whole cotton growth period, the Bt protein content in transgenic Bt cotton rhizosphere soil was higher than that in Bt cotton non-rhizosphere soil, and also, higher than that in common cotton rhizosphere soil, indicating that transgenic Bt cotton could release its Bt protein to rhizosphere soil.