MiR-203 regulates DJ-1 expression and affects proliferation, apoptosis and DDP resistance of pancreatic cancer cells.

OBJECTIVE: DJ-1 is a negative regulator of PTEN and plays a role in tumorigenesis. Abnormal miR-203 expression is associated with pancreatic cancer. Bioinformatics analysis showed a targeted relationship between miR-203 and DJ-1 3'-UTR. This study investigated whether miR-203 regulates DJ-1 expression and its role in pancreatic cancer cell proliferation, apoptosis, and cisplatin (DDP) resistance. MATERIALS AND METHODS: The Dual-Luciferase reporter gene assay validated the targeted regulation between miR-203 and DJ-1. The DDP-resistant cell line SW1990/DDP was established and divided into miR-NC group and miR-203 mimic group followed by analysis of the expression of DJ-1, PTEN and p-AKT, cell apoptosis, and proliferation. RESULTS: There was a targeted relationship between miR-203 and DJ-1 mRNA. The expression of miR-203 in SW1990/DDP cells was significantly lower than that in SW1990 cells, while the expression of DJ-1 mRNA and protein was significantly higher than that in SW1990 cells. Compared with miR-NC group, the expression of DJ-1 and p-AKT protein in SW1990/DDP cells was significantly decreased in miR-203 mimic transfection group, while the expression of PTEN was significantly increased with increased cell apoptosis and decreased cell proliferation, as well as reduced DDP resistance. CONCLUSIONS: The decreased expression of miR-203 and the increased expression of DJ-1 is associated with drug resistance in pancreatic cancer cells. Elevated miR-203 can inhibit the expression of DJ-1, affect the activity of PTEN-PI3K/AKT pathway, inhibit the proliferation of pancreatic cancer cells, induce cell apoptosis, and reduce DDP resistance of pancreatic cancer cells.

Exosomes and breast cancer: a comprehensive review of novel therapeutic strategies from diagnosis to treatment.

Exosomes are nanosized vesicles, released by various cells, which have essential roles in intercellular communication locally and systemically through transporting their contents such as proteins and lipids as well as RNA. It was clear that the element of contents in exosomes reassembled with the emerging of cancers. Over the past decade, researchers paid more attention to the role of exosomes in breast cancer. The purpose of this review was to discuss the details of the biological characteristics of exosomes in breast cancer. The discussion would focus on the role of exosomes in breast cancer development, progression, metastasis and drug resistance, as well as related therapeutic and diagnostic strategies.

Amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in migraine patients: a resting-state functional MRI study.

AIM: To evaluate the amplitude of low-frequency oscillations (LFOs) of the brain in migraine patients using amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in the interictal period, in comparison to healthy controls (HCs). MATERIALS AND METHODS: A total of 54 subjects, including 30 migraineurs and 24 gender- and age-matched HCs completed the fMRI. All the data and ALFF, fALFF analyses were preprocessed with the Data Processing Assistant for Resting-State fMRI (DPARSF). All of the statistical analyses were performed using the REST software to explore the differences in ALFF and fALFF between migraine patients and HCs. RESULTS: In contrast to HCs, migraine patients showed significant ALFF increase in the left medulla and pons, the bilateral cerebellum posterior lobe and right insula. The regions showing decreased ALFF in migraine patients included the bilateral cerebellum posterior lobe, left cerebellum anterior lobe, bilateral orbital cortex, right middle frontal gyrus, bilateral occipital lobe, right fusiform gyrus, and bilateral postcentral gyrus. The fALFFs in migraine patients were significantly increased in the bilateral insular and left orbital cortex, but were decreased in the left occipital lobe and bilateral cerebellum posterior lobe. CONCLUSION: These ALFF and fALFF alterations in the brain regions of migraineurs are in keeping with the domains associated with pain and cognition. Such brain functional alteration may contribute to further understanding of migraine-related network imbalances demonstrated in previous studies.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

Transforming growth factor beta 1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-ß1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-ß1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-ß1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-ß1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-ß1 and BMP-2.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Observed impacts of insulin therapy on callus cell transforming growth factor-beta 1 expression in diabetic rats.

The expression of transforming growth factor-beta 1 (TGF-ß1) inside the callus cells of diabetic rats and the impact of insulin therapy on its expression and biomechanics was investigated. The rats were randomly divided as follows: an insulin therapy group (IT), a diabetic model group (DM), and a non-diabetic control group (NC). Bone specimens from each group were extracted at different times for immunohistochemical observation of the expression of TGF-ß1. Concurrently, the destruction torque and torsional stiffness were detected at different times. One to four weeks after fracture, TGF-ß1 was widely expressed in fractured callus cells and periosteal proliferating cells, while the expression inside diabetic cells was significantly reduced. The expression of TGF-ß1 decreased over the first 68 weeks, and the mature bone cells never expressed TGF-ß1. The destruction torque (Nm) detected in the 6th week revealed that there was a statistically significant difference between the DM, NC, and IT groups (P < 0.01). In conclusion, TGF-ß1 expression was significantly reduced inside the callus cells of diabetic rats. Insulin therapy increased TGF-ß1 expression inside the callus cells of diabetic rats and improved the biomechanical characteristics of the callus.

Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.

Wilson's disease (WD), an autosomal recessive copper transport disorder, usually presents with symptoms involving the liver or central nervous system. The disease is caused by a large number of mutations in the ATP7B gene comprising 21 expressed exons. Some of the mutations appear to be population specific, whereas others are found in probands from a variety of different ethnic backgrounds. This paper presents the results of screening of the ATP7B gene by means of the direct sequencing of all exons in the gene in 39 Han and one Hui ethnic Chinese patients. Nineteen novel mutations were revealed along with nine others that have been previously described; 57.5% of the mutations were located in exons 8, 13, and 12. In particular, the Arg778Leu mutation in exon 8 was found in 55% of these Chinese patients in at least one allele. Five patients were homozygotes and 17 patients were heterozygotes for Arg778Leu. The detection rate on direct sequencing of the polymerase chain reaction products of all exons of the ATP7B gene in 40 unrelated patients was 83.8% of alleles. Seventeen polymorphisms were also identified in patients and healthy controls. We first reported the presence of ATP7B mutations in Chinese Hui ethnic patients and summarize our results here along with the previously reported findings. A significant correlation between genotype and phenotype was not found in 37 homozygotes and 52 heterozygotes for Arg778Leu.

Vasopressin-induced amber-like skin necrosis.

Case reports about vasopressin-induced cutaneous necrosis are not frequent. Here we report a further case, of which skin manifestations included not only mottling, cyanosis, ecchymosis, bullae and gangrene, but also amber-like change in focal areas. Besides, intermittent paling of the skin with or without deep pain sensation of the limbs over non-injection sites was observed that might be a warning sign of impending skin necrosis. Based on the literature about vasopressin-induced skin necrosis we discuss the possible role of coagulation enhancement of this molecule.