Giant lattice softening at a Lifshitz transition in Sr2RuO4.

The interplay of electronic and structural degrees of freedom in solids is a topic of intense research. More than 60 years ago, Lifshitz discussed a counterintuitive possibility: lattice softening driven by conduction electrons at topological Fermi surface transitions. The effect that he predicted, however, was small and has not been convincingly observed. Using a piezo-based uniaxial pressure cell to tune the ultraclean metal strontium ruthenate while measuring the stress-strain relationship, we reveal a huge softening of the Young's modulus at a Lifshitz transition of a two-dimensional Fermi surface and show that it is indeed driven entirely by the conduction electrons of the relevant energy band.

Mitochondrial quality control in cartilage damage and osteoarthritis: new insights and potential therapeutic targets.

Osteoarthritis (OA) is a multifactorial arthritic disease of weight-bearing joints concomitant with chronic and intolerable pain, loss of locomotion and impaired quality of life in the elderly population. Although the prevalence of OA increases with age, its specific mechanisms have not been elucidated and effective therapeutic disease-modifying drugs have not been developed. As essential organelles in chondrocytes, mitochondria supply energy and play vital roles in cellular metabolism, proliferation and apoptosis. Mitochondrial quality control (MQC) is the key mechanism to coordinate various mitochondrial biofunctions, primarily through mitochondrial biogenesis, dynamics, autophagy and the newly discovered mitocytosis. An increasing number of studies have revealed that a loss of MQC homeostasis contributes to the cartilage damage during the occurrence and development of OA. Several master MQC-associated signaling pathways and regulators exert chondroprotective roles in OA, while cartilage damage-related molecular mechanisms have been partially identified. In this review, we summarized known mechanisms mediated by dysregulated MQC in the pathogenesis of OA and latent bioactive ingredients and drugs for the prevention and treatment of OA through the maintenance of MQC.

Heat-capacity measurements under uniaxial pressure using a piezo-driven device.

We report the development of a technique to measure heat capacity at large uniaxial pressure using a piezoelectric-driven device generating compressive and tensile strain in the sample. Our setup is optimized for temperatures ranging from 8 K down to millikelvin. Using an AC heat-capacity technique, we are able to achieve an extremely high resolution and to probe a homogeneously strained part of the sample. We demonstrate the capabilities of our setup on the unconventional superconductor Sr2RuO4. By replacing thermometer and adjusting the remaining setup accordingly, the temperature regime of the experiment can be adapted to other temperature ranges of interest.

The value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer.

OBJECTIVE: To explore the clinical application value of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging combined with detection of serum tumor molecular markers (carbohydrate antigen 125 (CA 125) and human epididymis protein 4 (HE4)) in the diagnosis of recurrence and metastasis of ovarian cancer. PATIENTS AND METHODS: Clinical data about 18F-FDG PET/CT imaging and serum CA125 and HE4 of 69 ovarian cancer patients after the first cytoreductive surgery and chemotherapy were retrospectively analyzed, and the clinical application value of 18F-FDG PET/CT imaging combined with detection of CA125 and HE4 in the diagnosis of recurrence and metastasis of ovarian cancer was evaluated. RESULTS: The 18F-FDG PET/CT images of recurrence and metastasis of ovarian cancer showed hypermetabolism. The sensitivity, specificity, accuracy, predictive positive value, and predictive negative value of 18F-FDG PET/CT imaging for the diagnosis of recurrence and metastasis of ovarian cancer were 90.74%, 86.67%, 89.86%, 96.08%, and 72.22%, respectively; those of CA125 for the diagnosis of them were 77.78%, 86.67%, 79.71%, 95.45% and 52.00%, respectively, and those of HE4 for the diagnosis of them were 70.37%, 93.33%, 76.84%, 97.44%, and 48.39% respectively. In addition, the sensitivity and specificity of 18F-FDG PET/CT combined with detection of serum CA125 and HE4 for the diagnosis were 100.00% and 100.00%, respectively, significantly higher than those of separate 18F-FDG PET/CT imaging, detection of serum CA125, and detection of serum HE4 (c2 = 5.243, 13.500, 18.783, p = 0.022, 0.000, 0.000; c2 = 4.000, 8.525, 9.864, p = 0.046, 0.004, 0.002), and the accuracy of the combination use of them was 95.65%, also significantly higher than that of separate CA125 and HE4 (c2 = 8.118, 10.315, p = 0.004, 0.001, both p < 0.01). Furthermore, the maximum standardized uptake value (SUVmax) of 18F-FDG PET/CT imaging for recurrence and metastasis of ovarian cancer focuses was significantly positively correlated with serum CA125 and HE4 levels (r = 0.596, p = 0.000; r = 0.431, p = 0.002), and the serum CA125 level was also significantly positively correlated with serum HE4 level in patients with recurrent or metastasized ovarian cancer (r = 0.198, p = 0.043,). CONCLUSIONS: 18F-FDG PET/CT imaging combined with detection of serum CA125 and HE4 can significantly improve the diagnostic efficiency to recurrence and metastasis of ovarian cancer and is conducive to the early diagnosis of the recurrence and metastasis, which provides a basis for further clinical intervention.

CRKL promotes proliferation, migration, invasion of laryngeal squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the expression and role of CT10 regulated kinase like (CRKL) in human laryngeal squamous cell carcinoma (LSCC) progression. PATIENTS AND METHODS: Seventy-four laryngeal cancer cases were detected by the immunohistochemistry S-P method and the results were analyzed. RNA interference was used to downregulate the expression of CRKL in Hep-2 cells. The silencing efficiency was detected by real-time PCR and Western blotting. The cell proliferation, migration, and invasion after transfection were detected by MTT, wound healing assay, transwell invasion assay, and apoptosis assay. Western blot was conducted to determine the function of CRKL/epithelial-mesenchymal transition (EMT) signaling pathway. RESULTS: The expression of CRKL was higher in LSCC tissues. Patients with higher CRKL expression were correlated with lymph node metastasis and postoperative survival rates. CRKL promoted proliferation, migration, and invasion of Hep-2 cells in vitro. CONCLUSIONS: These findings suggested that CRKL gene silencing significantly inhibited the proliferation, migration, invasion, and EMT signaling pathway of Hep-2 cells. CRKL is considered to be a new target for the treatment of LSCC.

Effect of celecoxib on protein expression of FAK and Cx43 in DMBA induced rat tongue carcinoma cells.

OBJECTIVE: The pathogenesis of tongue cancer (TA) has not been fully illustrated. Cyclooxygenase-2 (COX-2) is correlated with the precancerous lesion of oral cavity mucosa and malignant transformation. The focal adhesion kinase (FAK) and gap junction protein connexin 43 (Cx43) are involved in the occurrence and progression of tumors. This study aimed to investigate the effect of celecoxib on the proliferation, malignant transformation, and expression of FAK and Cx43 proteins. MATERIALS AND METHODS: Healthy male Sprague-Dawley (SD) rats (4 months old) were divided into control, model and celecoxib group. 7,12-dimethylbenzanthracene (DMBA) was used to generate tongue mucosal carcinoma, coupled with celecoxib intervention. At 8, 12, 16, and 20 weeks after induction, the rat survival status, the tumor formation rate and the tongue tissue morphology were observed. Meanwhile, the expression of FAK and Cx43 was also evaluated by using immunohistochemistry (IHC). RESULTS: Tumor occurrence rates after induction were 0, 26.67%, 66.67%, and 80% at 8, 12, 16, and 20 weeks, respectively. The celecoxib treatment decreased such rats to 0, 0, 0, and 13.33%, respectively (p<0.05 compared to model group). No significant change was observed in control group, whilst model group had mild to severe hyperplasia and squamous carcinoma with elongated time. Celecoxib treatment significantly improved the tissue morphology (p<0.05). The model group also had elevated FAK and depressed Cx43 protein expression (p<0.05). With elongated time, the FAK expression was further increased whilst Cx43 protein was depressed (p<0.05 compared to model group). CONCLUSIONS: The focal application of celecoxib effectively inhibited the DMBA-induced rat TA, possibly via regulating FAK and CX43 protein expression, and inhibiting oral epidermal hyperplasia.

Comparative studies of mucosal humoral and cellular immune responses to 2009 pandemic H1N1 influenza virus in mice.

The nasal-associated lymphoid tissues (NALTs), embedded in the submucosa of murine upper respiratory tract, represents an important site of induction for local mucosal immune responses to airborne pathogens and intranasal vaccines. Here, we systematically investigated the mucosal humoral and cellular immune responses of NALTs in mice infected with A/Beijing/501/2009 (BJ501) and A/Puerto Rico/8/1934 (PR8) viruses. Compared with PR8 infection, BJ501 induced a more rapid increase of virus-specific IgA and IgG antibodies in the nasal lavage fluid and a higher ratio of IgG1/IgG2a, indicating a stronger Th2 response to BJ501 in mucosal immunity. In addition, using virus-specific enzyme-linked immunospot assay (ELISpot assay), we observed higher and earlier responses of virus-specific IgA and IgG antibody-secreting cells (ASCs) and IFN-γ and IL-4 cytokine-secreting cells (CSCs) in NALTs of mice intranasally infected with BJ501 virus. In particular, the frequency of BJ501-specific IFN-γ-CSCs significantly correlated with the kinetics of BJ501 virus load in NALTs, suggesting an important role of IFN-γ-CSCs-associated mucosal cellular immune responses in BJ501 virus clearance. Collectively, BJ501 induced a more comprehensive and rapid mucosal immune responses in NALTs of mice, providing further understanding of the immune responses elicited by 2009 pandemic H1N1 virus in upper respiratory tract. Keywords: nasal-associated lymphoid tissues (NALTs); influenza virus; mucosal immune response; Th1/Th2 response.

Up-regulation of long non-coding RNA SNHG6 predicts poor prognosis in renal cell carcinoma.

OBJECTIVE: We aim to investigate the expression of long non-coding RNA SNHG6 and analyze its clinicopathological significance in renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 81 cases of RCC tissues were collected and enrolled. Total RNA was extracted using the TRIzol method followed by qRT-PCR detection of the mRNA level of SNHG6. The x2-test was used to analyze the correlation between SNHG6 expression and clinicopathological variables, including age, gender, TNM stage, Fuhrman grade, tumor size, and overall prognosis. Kaplan-Meier survival curve was plotted to analyze the association between SNHG6 expression and overall survival. Univariate and multivariate analysis were carried out with the Cox proportional hazard analysis. RESULTS: SNHG6 was shown to be markedly upregulated in RCC tissues as compared with normal controls. Elevated SNHG6 was found to significantly correlate with clinical stage, lymph node metastasis, Fuhrman grade, and tumor size (p<0.05). Kaplan-Meier survival analysis exhibited that elevated SNHG6 was remarkably associated with poor overall survival (p<0.001). Moreover, multivariate analysis revealed that SNHG6 expression was an independent prognostic factor in RCC. CONCLUSIONS: We showed that up-regulated SNHG6 was significantly associated with tumor progression and was an independent prognostic factor in RCC, suggesting that SNHG6 can work as a promising prognostic predictor in RCC.

A clip domain serine protease involved in moulting in the silkworm, Bombyx mori: cloning, characterization, expression patterns and functional analysis.

Clip domain serine proteases (CLIPs), characterized by one or more conserved clip domains, are essential components of extracellular signalling cascades in various biological processes, especially in innate immunity and the embryonic development of insects. Additionally, CLIPs may have additional non-immune functions in insect development. In the present study, the clip domain serine protease gene Bombyx mori serine protease 95 (BmSP95), which encodes a 527-residue protein, was cloned from the integument of B. mori. Bioinformatics analysis indicated that BmSP95 is a typical CLIP of the subfamily D and possesses a clip domain at the N terminus, a trypsin-like serine protease (tryp_spc) domain at the C terminus and a conserved proline-rich motif between these two domains. At the transcriptional level, BmSP95 is expressed in the integument during moulting and metamorphosis, and the expression pattern is consistent with the fluctuating 20-hydroxyecdysone (20E) titre in B. mori. At the translational level, BmSP95 protein is synthesized in the epidermal cells, secreted as a zymogen and activated in the moulting fluid. Immunofluorescence revealed that BmSP95 is distributed into the old endocuticle in the moulting stage. The expression of BmSP95 was upregulated by 20E. Moreover, expression of BmSP95 was downregulated by pathogen infection. RNA interference-mediated silencing of BmSP95 led to delayed moulting from pupa to moth. These results suggest that BmSP95 is involved in integument remodelling during moulting and metamorphosis.

Neuromolecular imaging, a nanobiotechnology for Parkinson's disease: advancing pharmacotherapy for personalized medicine.

Evaluating each patient and animal as its own control achieves personalized medicine, which honors the hippocratic philosophy, explaining that "it is far more important to know what person has the disease than what disease the person has." Similarly, individualizing molecular signaling directly from the patient's brain in real time is essential for providing prompt, patient-based treatment as dictated by the point of care. Fortunately, nanotechnology effectively treats many neurodegenerative diseases. In particular, the new medicinal frontier for the discovery of therapy for Parkinson's disease is nanotechnology and nanobiotechnology. Indeed, the unique nanotechnology of neuromolecular imaging combined with the series of nanobiosensors enables continuous videotracking of molecular neurotransmitters in both the normal physiologic and disease states with long-term electrochemical operational stability. This nanobiotechnology is able to track a signal in real time with excellent temporal and spatial resolution directly from each patient's brain to a computer as subjects are behaving during movement, normal and/or dysfunctional including prion-like Parkinson's behavioral biometrics. Moreover, the molecular signaling performed by these nanobiosensors live streams directly online and originates from precise neuroanatomic brain sites such as, in this case, the dorsal striatum in basal ganglia. Thus, the nanobiotechnology studies discussed herein imaged neuromolecules with and without L-3,4-dihydroxyphenylalanine (L-DOPA) in dorsal striatal basal ganglia neurons. Parkinsonian and non-Parkinsonian animals were video-tracked, and images were readily seen on a laptop via a potentiostat using a semiderivative electrical circuit. Administered L-DOPA doses were 50 and 100 mg/kg intraperitoneally (ip); the same experimental paradigm was used to image and then contrast data. Results showed that the baseline release of biogenic amine molecules was significantly above detection limits in non-Parkinsonian animals. After administration of L-DOPA, biogenic amines significantly increased in these non-Parkinson's animals. Nevertheless, it is intriguing to see that L-DOPA could not enable synaptic dopamine release in Parkinson's animals, thereby demonstrating that biogenic amines are biomarkers for Parkinson's disease. Biomarkers are biochemical, genetic, or molecular measures of biological reactions. Importantly, there were other significant biomarkers present in Parkinsonian animals and absent in non-Parkinsonian animals; these were peptide neurotransmitters that include dynorphin and somatostatin in the brain with detection limits of 40 nM for dynorphin and 37 nM for somatostatin (see Table 1). Furthermore, L-DOPA significantly increased these peptide biomarkers, dynorphin and somatostatin, in Parkinson's animals. Targeting biomarkers enables new diagnostic devices and treatments for Parkinson's disease through nanotechnology and nanobiotechnology.

Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells.

A common feature of B-cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B-cell proliferation. However, CLL etiology remains unclear. CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B-cell antigen receptor (BCR) usage, autoreactivity with polyreactivity and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis. Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent. Here we identify an unmutated AMyIIA BCR in mouse, with distinctive CDR3 segments capable of promoting leukemogenesis. B cells with this AMyIIA BCR are generated by BCR-dependent signaling during B-1 fetal/neonatal development with CD5 induction, but not in adults. These early-generated AMyIIA B-1 B cells self-renew, increase during aging and can progress to become monoclonal B-cell lymphocytosis, followed by aggressive CLL in aged mice, often with the loss of a chromosomal region containing the miR15a/16-1 locus of varying length, as in human CLL. Thus, the ability to generate this defined autoreactive BCR by B-1 B cells is a key predisposing step in mice, promoting progression to chronic leukemia.

C-arm CT-guided renal arterial embolisation followed by radiofrequency ablation for treatment of patients with unresectable renal cell carcinoma.

AIM: To explore the value of using flat detector (FD) equipped angiographic C-arm CT (CACT) systems in treating unresectable renal cell carcinoma (RCC) by selective renal arterial embolisation (RAE) followed by radiofrequency ablation (RFA) (RAE-RFA). MATERIALS AND METHODS: A total of 28 patients who were not candidates for surgery were enrolled. The average size of tumours was 6.7±2.2 cm (range 4.1-9.6 cm). Twenty-eight tumours were treated with CACT-guided RFA, 5-7 days after CACT-guided RAE. RESULTS: CACT-guided RAE-RFA was technically successful in all patients. Tumour enhancement disappeared after a single RAE-RFA session in 20 patients, after two RAE-RFA sessions in four patients and after three RAE-RFA sessions in the other four patients. One patient died of lung metastasis and haematuria 13 months after RAE-RFA, and another patient died of pulmonary heart disease 23 months after repeat RAE-RFA. In the 26 living patients, tumours remained controlled during a mean follow-up period of 27 months and showed significant reduction in tumour size (6.7±2.2 cm to 3.9±1.7 cm, p<0.01). There were no significant changes in creatinine levels or urea nitrogen concentrations before and after the last RAE-RFA (p>0.05). There were no serious complications during and after the procedure. CONCLUSION: CACT-guided RAE followed by RFA appears to be a safe and effective technique for treating patients with inoperable RCC.

Biodegradable interstitial release polymer loading a novel small molecule targeting Axl receptor tyrosine kinase and reducing brain tumour migration and invasion.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the development of a BP wafer for a novel therapeutic strategy for treating GBM invasion and increasing survival in clinical subjects.

Effects of Astragaloside IV on diabetic nephropathy in rats.

The aims of this study were to explore the effects of Astragaloside IV on diabetic nephropathy (DN) rats. A total of 38 male Sprague-Dawley (SD) rats were divided into three groups: 10 in the normal (control) group, 14 in the DN model group, and 14 in the AS-IV group. Treatment began one week after the streptozotocin DN model was successfully established. Blood glucose and urine micro-albumin levels were measured every four weeks. After being treated for 12 weeks, all SD rats were sacrificed for blood and renal specimen collec-tion. Renal cortex specimens were observed after hematoxylin and eo-sin and Masson staining. Expression levels of protein ß1, ß1-integrin-linked protein kinase (ILK) and α-actinin-4 were also measured. After eight weeks of intervention, blood glucose levels in the AS-IV group decreased significantly when compared with those of the model group (P < 0.01). By the end of the twelfth week, the urine micro-albumin levels showed significant differences (P < 0.01) between the AS-IV and model groups, and the expression levels of integrin ß1, ILK, and α-actinin-4 also showed significant differences (P < 0.05, respectively). Concomitantly, expression levels of integrin ß1, ILK, and α-actinin-4 in the model group were significantly different from those of normal group (P < 0.05). These results suggest that AS-IV can be quite effective in decreasing blood glucose levels, reducing urine albumin excretion, and improving the adhesion function of potocytes, and can thus delay the development of DN.

Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer

Purpose: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. Materials and methods: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. Results: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPKsignaling pathway and PPAR signaling pathway. Conclusions: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress (AU)

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Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer.

PURPOSE: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND METHODS: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress.

Correlative study on risk factors of depression among acute stroke patients.

BACKGROUND: The causes of post-stroke depression (PSD) were complex, and it is hard to identify the consistent risk factors because the correlation may change along with time. AIM: To study the prevalence and multiple correlation factors of PSD in acute stroke patients. PATIENTS AND METHODS: The patients within over 2-6 weeks after stroke were collected and divided into depression group, depressive symptom group, and control group according to the Hamilton Depression Rating Scale for Depression. The NIH (National Institute of Health) Stroke Scale, the Barthel index (BI), the Instrumental Activities of Daily Living (IADL), and the Mini-Mental State Examination (MMSE) were respectively used to evaluate the neurologic impairment, Ability of Daily Life, and cognitive function of patients. RESULTS: PSD was associated with lower incomes (p < 0.05), but not associated with education level, medical insurance, and nature of the acute stroke (p > 0.05). The lesion location in the left hemisphere of the brain had a higher morbidity than that in the right hemisphere or both sides. There was a significant difference in the incidence of PSD between multifocal lesions and single lesion (p < 0.01). CONCLUSIONS: Lower income, cognitive dysfunctions, poor activities of daily life, poor social support, and history of hypertension and previous stroke were risk factors for the acute stroke patients to get depression. Stroke survivors with left hemisphere of the brain and more lesions (≥ 2) have more chance to get the PSD.

Role of 15-F2t-isoprostane in intestinal injury induced by intestinal ischemia/reperfusion in rats.

15-F2t-isoprostane is not only a specific marker of lipid peroxidation but also demonstrated to have potent bioactivities and can exert deleterious effects via activating thromboxane A2 receptor (TxA2r). We already demonstrated that lipid peroxidation represents a mechanism of intestinal ischemia/reperfusion (I/R) injury. But no studies have focused on 15-F2t-isoprostane production and its biological actions on postischemic intestine during intestinal I/R. This study was carried to investigate whether the mechanism of endogenous 15-F2t-isoprostane action is involved in the pathogenesis of intestinal I/R and administration of synthetic 15-F2t-isoprostane could exacerbate intestinal insult after intestinal I/R in vivo and in vitro. In comparison with that of the sham control, we reported that endogenous 15-F2t-isoprostane was liberated following intestinal I/R injury in rats, and using the TxA2r antagonist SQ29548 resulted in significant intestinal protection, evidenced by reduced lipid peroxidation, inflammation, and alleviated intestinal mucosal microvascular vasoconstriction. Further research found that in vivo administration of synthetic 15-F2t-isoprostane exacerbated intestinal I/R injury by disturbing microvascular perfusion and accumulating anaerobic metabolism. Meanwhile, 15-F2t-isoprostane did not change Hypoxia/Reoxygenation-induced IEC-6 cell viability but aggravated HUVECs cell death in vitro. Collectively, our results showed that locally produced 15-F2t-isoprostane was in proportion to the severity of oxidative stress-induced intestinal injury and its detrimental effects can be attenuated through TxA2r inactivation. Exogenous 15-F2t-isoprostane exacerbated intestinal I/R injury, which may be contributable to its biological actions on endothelium, rather than intestinal epithelium.

Involvement of nuclear factor κB (NF-κB) in the downregulation of cyclooxygenase-2 (COX-2) by genistein in gastric cancer cells.

Genistein induces growth inhibition in various human cancer cell lines but its mechanism of action remains unknown. This study determined whether the effect of genistein is mediated via suppression of cyclo-oxygenase (COX)-2 protein, and elucidated the mechanism of action of this effect in the human gastric cancer cell line BGC-823. Genistein treatment inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner; Western blotting analysis indicated a significant dose-dependent decrease in COX-2 protein levels. Genistein treatment exerted a significant inhibitory effect on activation of the transcription factor nuclear factor κB (NF-κB). Additionally, the NF-κB inhibitor pyrrolidine dithiocarbamate caused a reduction in COX-2 protein levels and NF-κB activation, similar to the effect of genistein. Suppression of COX-2 protein may be important for the antiproliferative and proapoptotic effects of genistein in BGC-823 cells, and these effects may be partly mediated through the NF-κB pathway.

Cell proliferation of human bone marrow mesenchymal stem cells on biodegradable microcarriers enhances in vitro differentiation potential.

OBJECTIVES: For reasons of provision of highly-specific surface area and three-dimensional culture, microcarrier culture (MC) has garnered great interest for its potential to expand anchorage-dependent stem cells. This study utilizes MC for in vitro expansion of human bone marrow mesenchymal stem cells (BMMSCs) and analyses its effects on BMMSC proliferation and differentiation. MATERIALS AND METHODS: Effects of semi-continuous MC compared to control plate culture (PC) and serial bead-to-bead transfer MC (MC bead-T) on human BMMSCs were investigated. Cell population growth kinetics, cell phenotypes and differentiation potential of cells were assayed. RESULTS: Maximum cell density and overall fold increase in cell population growth were similar between PCs and MCs with similar starting conditions, but lag period of BMMSC growth differed substantially between the two; moreover, MC cells exhibited reduced granularity and higher CXCR4 expression. Differentiation of BMMSCs into osteogenic and adipogenic lineages was enhanced after 3 days in MC. However, MC bead-T resulted in changes in cell granularity and lower osteogenic and adipogenic differentiation potential. CONCLUSIONS: In comparison to PC, MC supported expansion of BMMSCs in an up-scalable three-dimensional culture system using a semi-continuous process, increasing potential for stem cell homing ability and osteogenic and adipogenic differentiation.