MiR-615 inhibits cell proliferation, migration and invasion by targeting EGFR in human glioblastoma.

MiR-615 and epidermal growth factor receptor (EGFR) are associated with a number of disease processes and pathogenesis. However, little is known about the mechanisms of miR-615 and EGFR in human glioblastoma multiforme (GBM). Here, we found that down-regulation of miR-615 expression occurred in GBM tissues and cells, and was inversely correlated with overall survival, relapse-free survival, WHO grade as well as EGFR expression. We further determined that miR-615 functions as a tumor suppressor by inhibiting GBM cell proliferation, cell cycle, migration and invasion, and promoting cell apoptosis. In-vivo assay validated the inhibition effect of miR-615 on tumor growth and EGFR expression. Luciferase reporter assays demonstrated that miR-615 targeted the 3'-untranslated region (3'-UTR) of EGFR. Besides, over-expression of EGFR reversed the inhibition effects of miR-615, while silencing of EGFR aggravated these inhibition effects. In conclusions, we identified that miR-615 plays a tumor suppressor role in GBM cell proliferation, migration and invasion by targeting EGFR expression, and miR-615 may act as a novel biomarker for early diagnosis or therapeutic targets of GBM.

Arsenic induced overexpression of inflammatory cytokines based on the human urothelial cell model in vitro and urinary secretion of individuals chronically exposed to arsenic.

Chronic persistent inflammation could play an important role in the pathogenesis of some malignancies, and inflammation is a critical factor for bladder cancer development. In this study, we measured urine levels of transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α), and IL-8 in arsenic exposure workers and expressions of inflammatory cytokines in human urothelial cells in vivo and in vitro. We found the concentrations of IL-8, TNF-α, and TGF-α presented in urine were significantly elevated in the high urinary arsenic workers compared with the low urinary arsenic workers. Multiple regression analysis showed that the urinary IL-8 level was significantly positively associated with urinary iAs concentration after adjusting for the confounding effects of age, employed years, body mass index (BMI), smoking, alcohol, and seafood consumption in recent 3 days. Urinary TNF-α and TGF-α levels were also significantly positively associated with urinary iAs concentration, and SMI. TGF-α level was negatively associated with age after adjusting for the confounding effects. Consistent with the results in vivo, mRNA expressions of TNF-α, TGF-α, and IL-8 and protein expressions of TGF-α, TGF-ß1, and IL-8 were significantly elevated in SV-HUC-1 cells after exposure to lower concentrations of arsenite for 24h as compared to the control group. These data indicated that arsenic increased the secretion of inflammatory factors and IL-8, TNF-α, and TGF-α expression may be a useful biomarker of the effect of arsenic exposure.

Urinary VEGF and PGE2 levels and the association with arsenical metabolites in copper-smelting workers.

OBJECTIVES: To examine vascular endothelial growth factor (VEGF) and PGE2 levels in urine from the copper smelting workers exposed to arsenic and analyse the relationships between urinary VEGF or PGE2 level and arsenical metabolites. METHODS: The study was conducted in a group of 106 copper-smelting male workers. Information about each subject was obtained by questionnaire, inorganic As (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), VEGF and prostaglandin E2 (PGE2) in urine were determined. Standing height, body weight, and blood pressure were measured. RESULTS: According to the urine arsenic levels, participants were separated into three groups: Group 1: urine total arsenic <35 mg/L, Group 2: 35-100 mg/L, and Group 3: >100 mg/L. The median levels of urinary VEGF and PGE2 in Groups 1, 2 and 3 were 10.57 and 1032.0 pg/mL, 24.39 and 1060.9 pg/mL, and 49.0 and 1330.4 pg/mL, respectively. Urinary VEGF levels were positive associated with arsenical metabolites (iAs, MMA, DMA and TAs). Additionally, urinary VEGF and PGE2 levels were all correlated positively with the urinary MMA% (r=0.221, p=0.026 and r=0.206, p=0.037). While urinary VEGF was negatively with DMA% and secondary methylation index (r=-0.242, p=0.014 and r=-0.214, p=0.030, respectively). CONCLUSIONS: Urinary VEGF and PGE2 levels increased in arsenic exposure copper smelting workers, and urinary VEGF levels are well associated with the urinary arsenicals. This finding may provide useful information for developing measurement, prevention and treatment of damage induced by arsenic in the future.

Nanoquantification of RUNX2 by a 1,1'-carbonyldiimidazole-diamond mediated sandwich assay for osteogenic differentiation.

Adipose tissue-derived stem cells (ADSCs) possess the capability to modulate the immune response and alleviate inflammation, rendering them a promising therapeutic option for various conditions, including autoimmune diseases, cardiovascular diseases, and tissue injuries. The osteogenic differentiation in ADSCs plays a pivotal role in fracture healing, bone growth, and the overall bone turnover process, governed by intricate interactions. Runt-related Transcription Factor 2 (RUNX2) is a key player in mineralized tissue generation and is typically found in the early stages of osteogenic differentiation. The objective of this study was to develop a high-affinity sandwich biosensor for the quantification of RUNX2. 1,1'-Carbonyldiimidazole-modified nanodiamond was immobilized on an amine-modified interdigitated electrode surface, followed by the use of a capture antibody to facilitate antigen interaction. A sandwich assay was conducted with the antibody, and the limit of detection for RUNX2 was calculated as 0.1 ng/mL, with a regression value (R2) of 0.9914 over a linear range of 1-2000 ng/mL. Furthermore, biofouling experiments with a nonimmune antibody, BSA, and TNF-α did not yield any current responses, indicating the specific detection of RUNX2. Additionally, RUNX2-spiked serum exhibited an increasing current response at all concentrations, confirming the selective detection of RUNX2.

Artificial Intelligence-Based CT Imaging on Diagnosis of Patients with Lumbar Disc Herniation by Scalpel Treatment.

The aim of this study was to explore the application effect of computed tomography (CT) image based on active contour segmentation algorithm in the treatment of lumbar disc herniation (LDH) with scalpel. 78 patients with LDH were selected and divided into a lateral crypt block treatment group (group A) and a scalpel treatment group (group B) randomly. All the patients were examined by lumbar CT images based on artificial intelligence (AI) algorithm. Then, the clinical efficacy and Japanese orthopedic association (JOA) and visual analogue scale (VAS) scores were compared between the two groups. It was found that the total effective rate in group B was higher (92.31% vs. 84.62%) (P < 0.05). After treatment, the disc height (DH) in group A was obviously lower, and the vertebral body slippage was obviously higher (P < 0.05) than before. After treatment, there were more patients with nerve root location changes, edema, or disappearance in group B (P < 0.05). In contrast with JOA and VAS scores before treatment, both the groups showed obvious differences after treatment, especially group B (P < 0.05). Therefore, the CT images based on the AI algorithm can be used to analyze the treatment effect of LDH, and the scalpel treatment was more effective.

Calcitonin and Bone Physiology: In Vitro, In Vivo, and Clinical Investigations.

Calcitonin was discovered as a peptide hormone that was known to reduce the calcium levels in the systemic circulation. This hypocalcemic effect is produced due to multiple reasons such as inhibition of bone resorption or suppression of calcium release from the bone. Thus, calcitonin was said as a primary regulator of the bone resorption process. This is the reason why calcitonin has been used widely in clinics for the treatment of bone disorders such as osteoporosis, hypercalcemia, and Paget's disease. However, presently calcitonin usage is declined due to the development of efficacious formulations of new drugs. Calcitonin gene-related peptides and several other peptides such as intermedin, amylin, and adrenomedullin (ADM) are categorized in calcitonin family. These peptides are known for the structural similarity with calcitonin. Aside from having a similar structure, these peptides have few overlapping biological activities and signal transduction action through related receptors. However, several other activities are also present that are peptide specific. In vitro and in vivo studies documented the posttreatment effects of calcitonin peptides, i.e., positive effect on bone osteoblasts and their formation and negative effect on osteoclasts and their resorption. The recent research studies carried out on genetically modified mice showed the inhibition of osteoclast activity by amylin, while astonishingly calcitonin plays its role by suppressing osteoblast and bone turnover. This article describes the review of the bone, the activity of the calcitonin family of peptides, and the link between them.

Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise.

Depression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

The distribution in tissues and urine of arsenic metabolites after subchronic exposure to dimethylarsinic acid (DMAV) in rats.

Dimethylarsinic acid (DMA(V)) acted as cancer promoter promoted urinary bladder, liver, and lung carcinogenesis in rats. Understanding of the distribution of arsenicals in critical sites will aid to define the action of DMA(V)-induced toxicity and carcinogenicity. The present experiment was conducted to compare the accumulated levels of arsenicals in the liver, kidney, and bladder of both male and female rats after subchronic exposure to DMA(V). After exposure to DMA(V) in drinking water for 10 weeks, urinary DMA concentrations of 100 and 200 ppm DMA(V)-treated rats increased significantly compared with those of the control rats. Smaller amount of trimethylarsinic acid (TMA) was detected in urine, but not in liver, kidney, and bladder muscle. In the liver and kidney, the levels of DMA in DMA(V)-treated rats significantly increased compared with those of the control group, but there was no difference between 100 and 200 ppm DMA(V)-treated rats. DMA did not accumulate in bladder muscle. There was no difference for DMA concentrations between male and female rats. Our results suggest that the accumulation of DMA in the liver and kidney was saturated above 100 ppm DMA(V) treatment concentration, and DMA(V) was a little partly metabolized to TMA, and TMA was rapidly excreted into urine.

Effect of penehyclidine hydrochloride on heart rate variability in hysteroscopy.

In order to evaluate the effect of different doses of penehyclidine hydrochloride (penehyclidine) on heart rate (HR) and HR variability (HRV) in hysteroscopy, 180 patients (American Society of Anesthesiologists grade I-II) were randomized equally to three groups: 0.5 mg penehyclidine and intravenous anesthesia (group I), 1.0 mg penehyclidine and intravenous anesthesia (group II) and saddle anesthesia combined with intravenous anesthesia (control group). HR and HRV, including total power (TP), low-frequency power (LF), high-frequency power (HF) and the LF to HF ratio (LF/HF), were recorded prior and subsequent to the induction of anesthesia (T0 and T1, respectively), following the start of surgery (T2) and following completion of surgery (T3). HR was lower at T2 than at T0 in the control patients, but no differences were observed in groups I and II. The HR at T2 was increased in group II compared with that in group I. TP in group II was significantly higher compared with that in group I at T2. At T1 and at T2, the LF and HF values were lower in group I than those in the controls. Patients in group II also had higher LF and HF at T2 than patients in group I. The HF was higher at T2 than that at T0 in the controls; however, the HF and LF did not change significantly within groups I and II. No significant differences were observed in the LF/HF ratio among the three groups. At a dose of 0.5 mg, penehyclidine stabilized HRV and did not alter the autonomic nervous modulation of HR. A penehyclidine dose of 1.0 mg may be superior to a dose of 0.5 mg in maintaining HR, but is less effective at balancing sympathetic and parasympathetic activity.