Potential value of serum brain-derived neurotrophic factor, vascular endothelial growth factor, and S100B for identifying major depressive disorder in knee osteoarthritis patients.

Background: The chronic pain and functional limitations in osteoarthritis (OA) patients can increase risk of psychiatric disorders, e.g., major depression disorder (MDD), which may further aggravate the clinical symptoms of OA. Early detection of MDD is essential in the clinical practice of OA. Materials and methods: Two hundred and fifteen participants with knee OA were recruited, including 134 MDD patients (i.e., MDD group) and 81 ones without MDD (i.e., control group). Among them, 81 OA participants in the control group received a 3-year follow-up and were divided into trans-MDD group (who transforming into MDD; N = 39) and non-MDD group (who keeping non-MDD; N = 42) at the end of the follow-up. The 17-item Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), and Visual Analogue Scale (VAS) were performed. Furthermore, serum levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), S100B, and IGF-1 were detected. Results: (1) Compared with OA participants without MDD, there were significant decrease in serum BDNF and significant increase in serum VEGF and S100B and VAS scores in OA participants with MDD. (2) A mediation of the association was found between the VAS scores and the HAMD-17 scores through the BDNF as mediator in OA participants with MDD. (3) Significantly lower baseline BDNF levels and higher baseline S100B levels were detected in OA participants who transforming to MDD after a 3-year follow-up when compared with those who keeping non-MDD. (4) In the trans-MDD group, significant associations of the change of serum BDNF levels with rate of change of HAMD-17 scores were found, and baseline serum S100B levels positively correlated with the HAMD-17 scores at the end of the follow-up. (5) In OA participants, the composite indicator of BDNF, VEGF, and S100B differentiated MDD patients from controls with the area under the curve (AUC) value of 0.806, and the combined indicator of baseline BDNF and S100B distinguished trans-MDD participants from non-MDD ones with an AUC value of 0.806. Conclusion: Serum BDNF, VEGF, and S100B may be potential biomarkers to identify MDD in OA patients. Meanwhile, serum BDNF and S100B shows great potential to predict the risk of MDD for OA.

Plasma C1q/tumor necrosis factor-related protein-3 concentrations are associated with diabetic peripheral neuropathy.

INTRODUCTION: To analyze the associations of circulating C1q/tumor necrosis factor-related protein-3 (CTRP3) concentrations with several metabolic parameters and to investigate the possible role of CTRP3 in subjects with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: A total of 347 participants were recruited in this study, and plasma CTRP3 concentrations were analyzed in subjects with DPN (n=172) and without DPN (non-DPN, n=175). The nerve conduction test and oral glucose tolerance test were performed, and Neuropathy Symptom Score (NSS)/Neuropathy Disability Score (NDS) and biochemical parameters were measured in all participants. RESULTS: Plasma CTRP3 concentrations were significantly lower in patients with DPN compared with those in patients with diabetes without DPN (p<0.01), despite the comparable glucose and lipid metabolism levels in both groups. Groups with a higher plasma CTRP3 level had a faster nerve conduction velocity. In addition, plasma CTRP3 concentrations were negatively correlated with hemoglobin A1c (HbA1c), urea acid (UA), triglyceride, NSS and NDS (p<0.05) after being adjusted for age and sex. Multivariate logistic regression analysis revealed that plasma CTRP3 concentrations were significantly correlated with DPN after being controlled for age, sex, body mass index, HbA1c, blood pressure, lipid profiles, and renal function. CONCLUSIONS: Plasma CTRP3 concentrations were significantly lower in patients with DPM and positively correlated with nerve conduction velocity. The relationship between CTRP3 levels and DPN is independent of the glucose and lipid status. Therefore, circulating CTRP3 might serve as a predictor of impairment of nerve conduction in patients with DPN.

Circular RNA circ_0048764 promotes the development of breast cancer by regulating microRNA-1296-5p/tripartite motif containing 14 axis.

Breast cancer (BC) is one of the leading causes of cancer-related deaths in females. Circular RNA (circRNA), as reported, is involved in the progression of BC. This work focuses on clarifying the biological function of circ_0048764 in BC and its hidden mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of circ_0048764, microRNA-1296-5p (miR-1296-5p), and tripartite motif containing 14 (TRIM14) in BC tissues and cell lines. Besides, the status of proliferation, migration, invasion and apoptosis of BC cells was probed by cell counting kit-8 (CCK-8), EdU, transwell and flow cytometry assays. Western blot was adopted to examine the level of TRIM14 protein in BC cells. In addition, dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were conducted to corroborate the targeting relationships between miR-1296-5p and circ_0048764 or TRIM14. It was revealed that circ_0048764 expression was remarkably up-regulated in BC tissues and cells, and circ_0048764 expression was associated with TNM stage and tumor size. Functionally, overexpression of circ_0048764 significantly promoted BC cell proliferative, migrative and invasive abilities and inhibited apoptosis, while circ_0048764 knockdown exerted the opposite effects. Mechanistically, circ_0048764 directly targeted miR-1296-5p and could negatively modulate its expression in BC cells. Besides, miR-1296-5p could reverse the influence of circ_0048764 on BC viability, migration, invasion and apoptosis. Moreover, TRIM14 was confirmed to be a downstream target of miR-1296-5p. Circ_0048764 positively regulated TRIM14 expression in BC cells via targeting miR-1296-5p. Collectively, it is concluded that circ_0048764 promotes the development of BC via modulating the miR-1296-5p/TRIM14 axis.

Poloxamer surface modified trimethyl chitosan nanoparticles for the effective delivery of methotrexate in osteosarcoma.

The present work is an effort to explore the poloxamer-modified trimethyl chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve the therapeutic efficacy and minimize severe toxicity associated with the clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles (MTCN) was nanosized and exhibited a controlled release of drug from the carrier system. The MTCN showed higher accumulation in cell cytoplasm region evident by the high red fluorescence indicating its uptake through energy-dependent endocytosis process. MTCN exhibited the increased cytotoxicity in MG63 cells compared free MTX due to its enhanced cellular uptake. Especially, MTCN exhibited a superior apoptosis effect with bright chromatin condensation and nuclear fragmentation was observed and showed remarkably higher apoptosis (∼48%) compared to that of free drug. The results of this investigation clearly demonstrate that the poloxamer-modified trimethyl chitosan (TMC) seems to have a great potential as a drug carrier in cancer chemotherapy. The present research work offers immense scope for further exploitation of poloxamer-modified trimethyl chitosan (TMC) in future for the development of nanoparticulate drug delivery system for cancer chemotherapy.

Heparanase confers a growth advantage to differentiating murine embryonic stem cells, and enhances oligodendrocyte formation.

Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage. Embryonic stem (ES) cells overexpressing HPSE (Hpse-Tg) proliferated more rapidly than WT ES cells in culture and formed larger teratomas in vivo. In addition, differentiating Hpse-Tg ES cells also had a higher growth rate, and overexpression of HPSE in NSPCs enhanced Erk and Akt phosphorylation. Employing a two-step, monolayer differentiation, we observed an increase in HPSE as wild-type (WT) ES cells differentiated into neural stem and progenitor cells followed by down-regulation of HPSE as these NSPCs differentiated into mature cells of the neural lineage. Furthermore, NSPCs overexpressing HPSE gave rise to more oligodendrocytes than WT cultures, with a concomitant reduction in the number of neurons. Our present findings emphasize the importance of HS, in neural differentiation and suggest that by regulating the availability of growth factors and, or other macromolecules, HPSE promotes differentiation into oligodendrocytes.