The mammalian cell nucleus is highly structured and organized into various membrane-less nuclear compartments called nuclear bodies. Nuclear bodies are highly dynamic structures, with a variety of substances gathered inside to promote the more efficient conduct of certain biological reactions. It dynamically produces responses under different biological processes and stress conditions such as tumorigenesis, apoptosis, antiviral defense, and plays an important role in regulating cell homeostasis. Tumor is a major public health problem, and finding new targets is the key to tumor therapy. How the nuclear bodies are involved in the development of tumor has not been reported. This review aims to provide a new understanding of how the nuclear bodies regulates tumor progression and provide a new effective strategy for tumor prevention and treatment.

OBJECTIVE: Over-expression of thrombin in ovarian cancer cells is associated with poor prognosis. In this study, we investigated the role of thrombin in inducing epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells. METHODS: After thrombin treatment SKOV3 cells were subjected to western blots, reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT-related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was evaluated using transwell assays. RESULTS: The results indicated a dose- and time-dependent down-regulation of E-cadherin and upregulation of N-cadherin and vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control group (p<0.05). There was a dose- and time-dependent increase in the levels of SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin-treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3 cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6 and increased invasion compared to untreated cells (p<0.05). Thrombin altered the morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to thrombin-treated cells reversed the effects of thrombin. CONCLUSION: Thrombin induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that anticoagulant therapy could be a novel therapeutic strategy for ovarian carcinoma.
Blotting, Western ; Cadherins ; Cytokines ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Epithelial-Mesenchymal Transition ; Hirudins ; Interleukin-6 ; Interleukins ; Matrix Metalloproteinases ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Phenotype ; Polymerase Chain Reaction ; Prognosis ; Proteins ; RNA, Messenger ; Thrombin ; Up-Regulation ; Vimentin

BACKGROUNDFood composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 (GLP-1), ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus.

METHODSThe study enrolled 57 patients with type 2 diabetes (20 men and 37 women, mean age (67.05 ± 8.26) years). Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet.

RESULTSThe delta (2h - 0h) of C- peptide in meal A was significantly lower than that in meal B (P = 0.0004). C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A (P < 0.0001, < 0.0001, = 0.001, = 0.0004 respectively). Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P = 0.0005, 0.0079 respectively). Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (r(A0h) = 0.7836, r(B0h) = 0.9368, r(A2h) = 0.7615, r(B2h) = 0.9409, r(A(2h-0h)) = 0.7531, r((2h-0h))B = 0.9980, respectively, P < 0.0001).

CONCLUSIONWestern style meal (high fat and protein food) could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones (GLP-1, ghrelin) and brain peptide (EM-1) at the first phase of digestion.

Aged ; C-Peptide ; blood ; Diabetes Mellitus, Type 2 ; blood ; Diet ; Fasting ; blood ; Female ; Ghrelin ; blood ; Glucagon-Like Peptide 1 ; blood ; Humans ; Male ; Middle Aged ; Oligopeptides ; blood ; Postprandial Period

BACKGROUNDFunctional imaging studies indicate abnormal activities in cortico-limbic network in depression during either task or resting state. The present work was to explore the abnormal spontaneous activity shown with regional homogeneity (ReHo) in depression by resting-state functional magnetic resonance imaging (fMRI).

METHODSUsing fMRI, the differences of regional brain activity were measured in resting state in depressed vs. healthy participants. Sixteen participants firstly diagnosed with major depressive disorder and 16 controls were scanned during resting state. A novel method based on ReHo was used to detect spontaneous hemodynamic responses across the whole brain.

RESULTSReHo in the left thalamus, left temporal lobe, left cerebellar posterior lobe, and the bilateral occipital lobe was found to be significantly decreased in depression compared to healthy controls in resting state of depression.

CONCLUSIONSAbnormal spontaneous activity exists in the left thalamus, left temporal lobe, left cerebellar posterior lobe, and the bilateral occipital lobe. And the ReHo may be a potential reference in understanding the distinct brain activity in resting state of depression.

Adult ; Case-Control Studies ; Depressive Disorder, Major ; pathology ; Female ; Hemodynamics ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Occipital Lobe ; pathology ; Temporal Lobe ; pathology ; Thalamus ; pathology ; Young Adult

BACKGROUNDReports on mood regulating circuit (MRC) indicated different activities between depressed patients and healthy controls. The functional networks based on MRC have not been described in major depression disorder (MDD). Both the anterior cingulate cortex (ACC) and thalamus are all the key regions of MRC. This study was to investigate the two functional networks related to ACC and thalamus in MDD.

METHODSSixteen patients with MDD on first episode which never got any medication and sixteen matched health controls were scanned by 3.0 T functional magnetic resonance imaging (fMRI) during resting-state. The pregenual anterior cingulate cortex (pgACC) was used as seed region to construct the functional network by cortex section. The thalamus was used as seed region to construct the functional network by limbic section. Paired-t tests between-groups were performed for the seed-target correlations based on the individual fisher z-transformed correlation maps by SPM2.

RESULTSDepressed subjects exhibited significantly great functional connectivity (FC) between pgACC and the parahippocampus gyrus in one cluster (size 923) including left parahippocampus gyrus (-21, -49, 7), left parietal lobe (-3, -46, 52) and left frontal lobe (-27, -46, 28). The one cluster (size 962) of increased FC on thalamus network overlapped the precuneus near to right parietal lobe (9, -52, 46) and right cingulate gyrus (15, -43, 43) in health controls.

CONCLUSIONSAbnormal functional networks exist in earlier manifestation of MDD related to MRC by both cortex and limbic sections. The increased functional connectivity of pgACC and decreased functional connectivity of thalamus is mainly involved in bias mood processing and cognition.

Adult ; Depressive Disorder, Major ; physiopathology ; Female ; Gyrus Cinguli ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Thalamus ; physiopathology

OBJECTIVETo study the effect of telomerase reverse transcriptase (TERT) on cell apoptosis in neonatal rat brains after hypoxic-ischemic brain injury (HIBD).

METHODSA total of 72 neonatal rats were divided into sham, vehicle, HIBD and TERT groups. HIBD was induced by Rice method in the later three groups. The neonatal rats in the vehicle and TERT groups were injected with plasmids containing mock or full length TERT by an intracerebroventricular injection 30 minutes after hypoxic-ischemic (HI) injury. Pathological changes of brain tissue were observed by hematoxylin and eosin (HE) staining. Western blot was used to detect the protein expression of TERT, apoptosis-inducing factor (AIF) and cleaved caspase 3 (CC3). Apoptotic cells were detected by TUNEL staining.

RESULTSWestern blot showed that TERT protein was dramatically increased in the vehicle, HIBD and TERT groups compared with the sham group. Compared with the vehicle and HIBD groups, TERT protein in the TERT group was significantly upregulated. Compared with the sham group, there was a significant increase in apoptotic index and expression of AIF and CC3 proteins in the vehicle and HIBD groups (p<0.01). The TERT group showed decreased expression of AIF and CC3 proteins and apoptotic index compared with the vehicle and HIBD groups (p<0.01).

CONCLUSIONSTERT can inhibit cell apoptosis induced by HI and might have a neuroprotective role in developing brain with HIBD.

Animals ; Animals, Newborn ; Apoptosis ; Caspase 3 ; metabolism ; Hypoxia-Ischemia, Brain ; pathology ; therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Telomerase ; genetics

OBJECTIVETo extract the active component from the root of Actinidia valvata Dunn and to investigate the effects on hepatocellular carcinoma (HCC) cells in vitro.

METHODSTotal saponin was extracted from the root of A. valvata (TSAVD). HCC cells, such as BEL-7402, HepG2, PLC, SMMC-7721, MHCC-97-H, and MHCC-97-L, were treated with TSAVD in 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide (MTT) assay. BEL-7402 and MHCC-97-H cells were also treated respectively with TSAVD at different concentrations for 24 h in wound healing and adhesion assays, and the effects of TSAVD on BEL-7402 and MHCC-97-H cells mobility and adhesion abilities were observed. Meanwhile, the effects of TSAVD on invasion and migration of BEL-7402 and MHCC-97-H cells were also investigated by transwell chamber in invasion and migration assays.

RESULTSTSAVD at 1.5 mg/mL inhibited BEL-7402 cell proliferation with inhibition ratios (IRs) of 61.08%, 74.12%, 84.55% at 24, 48, and 72 h, respectively. Meanwhile, TSAVD inhibited MHCC-97-H proliferation in a concentration-dependent manner from 1.5 to 0.5 mg/mL, with the IR of 36% at 1.5 mg/mL at 24 h. For SMMC-7721, PLC, and HepG2, the IR was lower than 30% at 1.5 mg/mL at 24 h. In the wound healing assay, mobility abilities of BEL-7402 and MHCC-97-H cells in TSAVD treated groups were significantly weaker than those of the control group. After pretreatment for 24 h with TSAVD, adhesion abilities were reduced in both MHCC-97-H and BEL-7402 cells, with IRs of 48.50%±4.86% and 49.85%±5.25% at 200 μg/mL. The IRs of MHCC-97-H and BEL-7402 cells in the migration assay were 49.13%±2.91% and 79.37%±0.09% at 200 μg/mL. In the invasion assay, IRs were 69.78%±4.88% and 82.48%±0.25% at 200 μg/mL.

CONCLUSIONSOf all HCC cells, the highest inhibition by TSAVD was seen for BEL-7402 proliferation. TSAVD could restrain adhesion, invasion, mobility, and migration abilities of BEL-7402 and MHCC-97-H cells in vitro.

Actinidia ; chemistry ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Adhesion ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drug Screening Assays, Antitumor ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; drug therapy ; prevention & control ; Plant Roots ; chemistry ; Saponins ; pharmacology ; therapeutic use ; Wound Healing ; drug effects

With the development and improvement of new sequencing technology, next-generation sequencing (NGS) has been applied increasingly in cancer genomics research over the past decade. More recently, NGS has been adopted in clinical oncology to advance personalized treatment of cancer. NGS is used to identify novel and rare cancer mutations, detect familial cancer mutation carriers, and provide molecular rationale for appropriate targeted therapy. Compared to traditional sequencing, NGS holds many advantages, such as the ability to fully sequence all types of mutations for a large number of genes (hundreds to thousands) in a single test at a relatively low cost. However, significant challenges, particularly with respect to the requirement for simpler assays, more flexible throughput, shorter turnaround time, and most importantly, easier data analysis and interpretation, will have to be overcome to translate NGS to the bedside of cancer patients. Overall, continuous dedication to apply NGS in clinical oncology practice will enable us to be one step closer to personalized medicine.
High-Throughput Nucleotide Sequencing ; economics ; methods ; Humans ; Mutation ; Neoplasms ; genetics ; Precision Medicine ; Sequence Analysis, DNA

OBJECTIVETo explore the efficiency of a comprehensive surgical approach of genioglossus advancement and hyoid suspension (GAHM) plus uvulopalatopharyngoplasty (UPPP) for treating severe obstructive sleep apnea hypopnea syndrome (OSAHS) and to evaluate related factors on surgery outcomes.

METHODSEighteen patients with severe OSAHS (apnea hypopnea index, AHI > 40/h) confirmed with polysomnography received genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty. The obstruction in both the oropharynx and the hypopharynx were evaluated by preoperative physical examination, fiberoptic pharyngolaryngoscopy, cephalometry, and computed tomography of the upper airway. The follow up was at least 6 months postoperatively. The Wilcoxon signed rank test was used to compare the preoperative and postoperative results by SPSS 11.0 for windows. The Mann-Whitney test was used to analyze the difference between responders and nonresponders.

RESULTSThe follow up time ranges from 6 to 24 months, there were statistically significance in all but body mass index (BMI) between preoperative and postoperative measurements. Mean AHI was reduced from preoperative (x +/- s, 63.8 +/- 16.3)/h to postoperative (23.6 +/- 19.5)/h, lowest mean oxygen saturation increased from 0.72 +/- 0.07 to 0.81 +/- 0.13(x +/- s). According to criterion at home, the 6-month rate of responder is 83%, if AHI <20/h and decreased by at least 50% as success, the rate of success is 67%. The age, posterior airway space (PAS) and percentage of time with oxyhemoglobin saturation below 0.90 (CT90) were (39.1 +/- 7.4) years, (8.3 +/- 0.9) mm, (18.5 +/- 10.9)% in responder, while (52.5 +/- 9.4) years, (6.8 +/- 1.3) mm, (37.7 +/- 23.6) % in nonresponder, and there are statistically significant between responder and nonresponder.

CONCLUSIONSGAHM plus UPPP is effective surgical approach for patients with severe OSAHS who suffer from oropharyngeal and hypopharyngeal obstruction. Age, PAS and CT90 were possible affective factors on surgical outcomes.

Adult ; Aged ; Humans ; Hyoid Bone ; surgery ; Male ; Middle Aged ; Otorhinolaryngologic Surgical Procedures ; methods ; Palate, Soft ; surgery ; Polysomnography ; Sleep Apnea, Obstructive ; surgery ; Treatment Outcome ; Uvula ; surgery