Human Bone Marrow Derived-Mesenchymal Stem Cells Treatment for Autoimmune Premature Ovarian Insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a relatively common gynecologic endocrine disorder, which is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. POI resulting from ovarian autoimmunity is a poorly understood clinical condition lacking effective treatments. This study is aimed to investigate the therapeutic effect of mesenchymal stem cells (MSCs) on autoimmune premature ovarian insufficiency. METHODS: In this study, in vivo and in vitro experiments were conducted to clarify the therapeutic effects and possible mechanisms of human bone marrow-derived MSCs (hBMSCs) on autoimmune POI, and to provide an experimental evidence for the treatment of autoimmune POI by hBMSCs. Noteworthy, in this study, we used interferon-gamma (IFN-γ) to induce autoimmune inflammation in human granulosa cell line KGN, simulating the pathophysiological changes of granulosa cells in autoimmune POI, and therefore sought to establish an in vitro cell model of autoimmune POI, which is still lacking in experimental methodology. RESULTS: And we found that, in vitro, co-culture of hBMSCs could promote granulosa cell proliferation, inhibit apoptosis, improve hormone synthesis capacity, and reduce the occurrence of pyroptosis; and in vivo, hBMSCs resulted in improved estrous cycle disorders in autoimmune POI mice, increased serum estradiol, decreased follicle-stimulating hormone, improved ovarian morphology, increased number of primordial and primary follicles, decreased number of atretic follicles, and decreased ovarian granulosa cell apoptosis. CONCLUSIONS: hBMSCs have therapeutic effects on autoimmune POI both in vitro and in vivo.

Diagnostic performance of gadoxetic acid-enhanced abbreviated magnetic resonance imaging protocol in small hepatocellular carcinoma (≤2 cm) in high-risk patients.

BACKGROUND: Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time. PURPOSE: To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients. MATERIAL AND METHODS: Two hundred and four consecutive patients with 166 pathologically confirmed small HCC who underwent preoperative gadoxetic acid-enhanced MRI were retrospectively included. A-MRI set comprised T1-weighted hepatobiliary phase imaging, T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient mapping. Two independent radiologists blinded to clinical data assessed the A-MRI set and F-MRI set. Per-patient HCC and per-lesion HCC diagnostic performance were compared. RESULTS: Per-patient HCC detection sensitivity of A-MRI set was 93.8% and 91.2% for observer 1 and observer 2, and, for the F-MRI set, the per-patient HCC detection sensitivity was 96.6% and 95.2%, respectively. There was no significant difference in per-patient sensitivity, specificity and per-lesion HCC detection sensitivity between the two imaging sets for both readers. (P = 0.06-0.25) The A-MRI set showed higher sensitivity on HCC without arterial phase hyperenhancement, and the F-MRI set demonstrated with higher sensitivity on HCC with arterial phase hyperenhancement (P < 0.05). CONCLUSION: A-MRI using diagnostic criteria including hypointensity on hepatobiliary phase plus mild to moderate hyperintensity on T2-weighted imaging or restricted diffusion demonstrated comparable sensitivity and specificity for small HCC compared to the F-MRI protocol in high-risk patients.

Prognostic value of preoperative CT features for disease-free survival in patients with primary gastric gastrointestinal stromal tumors after resection.

PURPOSE: Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs. METHODS: 132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed. We used a certain CT attenuation of 30 HU to extract the enhancing tissue component from the tumor. Enhancing tissue volume and other CT features were assessed on venous-phase images. We evaluated the value of preoperative CT features for predicting the DFS after surgery. Univariate and multivariate Cox regression analyses were performed to find the independent risk factor for predicting the DFS. RESULTS: Of the 132 patients, 68 were males and 64 were females, with a mean age of 61 years. The median follow-up duration was 60 months, and 28 patients experienced disease recurrence and distant metastasis during the follow-up period. Serosal invasion (p < 0.001; HR = 5.277) and enhancing tissue volume (p = 0.005; HR = 1.447) were the independent risk factors for predicting the DFS after curative resection for patients with primary gastric GISTs. CONCLUSION: Preoperative contrast-enhanced CT could be useful for predicting the DFS after the surgery of gastric GISTs, and serosal invasion and enhancing tissue volume were the independent risk factors.

[Role of M2 Macrophage Exosomes in Osteogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells under High-Glucose and High-Insulin].

OBJECTIVE: To study the role of M2 macrophage-derived exosomes (M2-exo) in osteogenic differentiation and Hedgehog signaling pathway of mouse bone marrow mesenchymal stem cells (BMSCs) under in vitro high-glucose and high-insulin conditions. METHODS: RAW 264.7 cells were induced toward M2 macrophage polarization and then M2-exo were extracted and identified. Immunofluorescence assay was performed to detect the internalization of M2-exo by BMSCs. BMSCs were divided into the normal control group (Control group), the high-glucose and high-insulin group (HGI group), and the HGI with M2-exo intervention group (HGI+M2e group). BMSCs in the Control group were cultured in osteogenic inductive medium with 5.5 mmol/L glucose, but no insulin or M2-exo. BMSCs in the HGI group were cultured in osteogenic inductive medium with 25 mmol/L glucose and 174 nmol/L insulin. BMSCs in the HGI+M2e group were cultured in the same medium as that of the HGI group, with the additional treatment of 6, 30, 60 µg/mL M2-exo, respectively. After osteogenic induction for 7 days and 14 days, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively to assess the osteogenic differentiation potential of BMSCs from different groups. In addition, BMSCs in the Control group, HGI group, and HGI+M2e group treated with 30 µg/mL M2-exo were examined with qPCR after osteogenic induction for 14 days and Western blot after osteogenic induction for 21 days to assess the osteogenesis and the expression of Hedgehog pathway-related genes and proteins. RESULTS: M2 macrophage polarization was induced successfully, with highly positive expression of CD206, the M2 polarization surface marker. The M2-exo had the typical structure of round or oval-shaped bilayered-membrane vesicles. The diameter distribution of M2-exo ranged from 50 to 125 nm (accounting for 99.14% of all M2-exo). M2-exo samples showed positive expression of exosomal markers CD9, CD63 and CD81 proteins. Immunofluorescence staining showed that M2-exo were taken up and internalized by BMSCs. After osteogenic induction for 7 days, the ALP activity of BMSCs in the HGI group was lower than that of the Control group. After interventions of 6 µg/mL, 30 µg/mL, and 60 µg/mL M2-exo, the ALP activity of the HGI+M2-exo group was significantly increased compared with that of the HGI group ( P<0.05). After osteogenic induction for 14 days, the number of mineralized nodules in the HGI group was lower than that in the Control group, and after intervention, only the HGI+M2e group treated with 30 µg/mL M2-exo showed higher level of mineralization than that in the HGI group ( P<0.05). qPCR analysis revealed that the expression levels of the osteogenesis-related genes, including Runx2, Alp and Ocn, and Hedgehog pathway-related genes, including Gli1, Smo and Ptch1, were downregulated in the HGI group, all being lower than those of the Control group to varying degrees, while 30 µg/mL M2-exo treatment could promote the up-regulation of these genes, showing significant difference in comparison with their expression levels in the HGI group ( P<0.05). In addition, Western blot analysis showed that the expression of the osteogenesis-related proteins, including RUNX2 and COL1A1, and GLI1, the Hedgehog signaling pathway protein, was down-regulated in the HGI group, while the expression of COL1A1 and GLI1 was up-regulated after 30 µg/mL M2-exo treatment, showing significant difference when compared with that of the HGI group ( P<0.05). CONCLUSION: High glucose and high insulin had inhibitory effect on the osteogenic differentiation potential of BMSCs. After intervention with M2-exo, the Hedgehog signaling pathway in BMSCs was activated and the osteogenic differentiation potential was enhanced, suggesting that M2-exo might have therapeutic potentials for the treatment of diabetic bone disease.

Microvascular invasion of small hepatocellular carcinoma can be preoperatively predicted by the 3D quantification of MRI.

OBJECTIVES: To explore the importance of three-dimensional (3D) quantitative analysis during gadoxetic acid-enhanced magnetic resonance imaging (MRI) of microvascular invasion (MVI) and early recurrence (< 2 years) after surgery of single hepatocellular carcinoma (HCC) ≤ 3 cm. METHODS: Two hundred fourteen patients with pathologically confirmed HCC (training cohort: n = 169; validation cohort: n = 45) were included retrospectively. The 3D quantitative parameters (volume, sphericity, and compacity) and conventional MRI features were analyzed. The significant predictors for MVI were identified using univariate and multivariate logistic regression analyses. Nomograms were constructed from the prediction model, and the relationship between the significant predictors and early recurrence rates was evaluated using the Kaplan-Meier method. RESULTS: Tumor sphericity (odds ratio [OR] = 0.000; p < 0.001), non-smooth tumor margin (OR = 3.353; p = 0.015), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 14.067; p = 0.003) were independent significant factors for MVI. When these three factors were combined, the diagnostic specificity of the training and validation cohorts was 97.0 (128/132) and 87.9 (29/33), respectively. The nomogram based on the predictive model performed satisfactorily in the training (C-index: 0.885) and validation (C-index: 0.869) cohorts. Early recurrence rates of patients with two or three significant factors were significantly higher than those with none in the training (29.1% vs. 10.2%, p = 0.007) and validation (36.4% vs. 6.7%, p = 0.037) cohorts. CONCLUSIONS: Lower sphericity combined with non-smooth tumor margin and peritumoral hypointensity on HBP are potential predictive factors for MVI and associated with early recurrence after surgery of HCC ≤ 3 cm. KEY POINTS: • Lower sphericity, non-smooth tumor margin, and peritumoral hypointensity on HBP were important indicators of the occurrence of MVI in HCC. • The combinational model prepared from these findings satisfactorily predicted MVI, and the presence of these predictors was associated with an early recurrence rate after surgical resection in HCC patients. • This model could help clinicians in the preoperative management of small HCC ≤ 3 cm.

Hepatobiliary phase images of gadoxetic acid-enhanced MRI may improve accuracy of predicting the size of hepatocellular carcinoma at pathology.

BACKGROUND: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used in clinical practice. However, scientific evidence is lacking for recommending a particular sequence for measuring tumor size. PURPOSE: To retrospectively compare the size of hepatocellular carcinoma (HCC) measured on different gadoxetic acid-enhanced MRI sequences using pathology as a reference. MATERIAL AND METHODS: A total of 217 patients with single HCC who underwent gadoxetic acid-enhanced MRI before surgery were included. The size of the HCC was measured by two abdominal radiologists independently on the following sequences: T1-weighted; T2-weighted; b-500 diffusion-weighted imaging (DWI); and arterial, portal venous, transitional, and hepatobiliary phases. Tumor size measured on MRI was compared with pathological size by using Pearson correlation coefficient, independent-sample t test, and Bland-Altman plot. Agreement between two readers was evaluated with intraclass correlation coefficient (ICC). RESULTS: Correlation between the MR images and pathology was high for both readers (0.899-0.955). Absolute error between MRI and pathologic assessment was lowest on hepatobiliary phase images for both readers (reader 1, 2.8±4.2 mm; reader 2, 3.2±3.4 mm) and highest on arterial phase images for reader 1 (4.9±4.4 mm) and DWI phase images for reader 2 (5.1±4.9 mm). Absolute errors were significantly different for hepatobiliary phase compared with other sequences for both readers (reader 1, P≤0.012; reader 2, P≤0.037). Inter-reader agreements for all sequence measurements were strong (0.971-0.997). CONCLUSION: The performance of gadoxetic acid-enhanced MRI sequences varied with HCC size, and the hepatobiliary phase may be optimal among these sequences.

Utility of preoperative computed tomography features in predicting the Ki-67 labeling index of gastric gastrointestinal stromal tumors.

PURPOSE: To evaluate the value of preoperative computed tomography (CT) features including morphologic and quantitative features for predicting the Ki-67 labeling index (Ki-67LI) of gastric gastrointestinal stromal tumors (GISTs). METHODS: We retrospectively included 167 patients with gastric GISTs who underwent preoperative contrast-enhanced CT. We assessed the morphologic features of preoperative CT images and the quantitative features including the maximum diameter of tumor, total tumor volume, mean total tumor CT value, necrosis volume, necrosis volume ratio, enhanced tissue volume, and mean CT value of enhanced tissue. Potential predictive parameters to distinguish the high-level Ki-67LI group (>4%, n = 125) from the low-level Ki-67LI group (≤4%, n = 42) were compared and subsequently determined in multivariable logistic regression analysis. RESULTS: Growth pattern (p = 0.036), shape (p = 0.000), maximum diameter (p = 0.018), total tumor volume (p = 0.021), mean total tumor CT value (p = 0.009), necrosis volume (p = 0.006), necrosis volume ratio (p = 0.000), enhanced tissue volume (p = 0.027), and mean CT value of enhanced tissue (p = 0.004) were significantly different between the two groups. Multivariate logistic regression analysis indicated that lobulated/irregular shape (odds ratio [OR] = 3.817; p = 0.000) and high necrosis volume ratio (OR = 1.935; p = 0.024) were independent factors of high-level Ki-67LI. CONCLUSIONS: Higher necrosis volume ratio in combination with lobulated/irregular shape could potentially predict high expression of Ki-67LI for gastric GISTs.

CT-detected extramural venous invasion is corelated with presence of lymph node metastasis and progression-free survival in gastric cancer.

OBJECTIVE: This study aimed to investigate if CT-detected extramural venous invasion (ctEMVI) was associated with the presence of lymph node metastasis (LNM) and survival outcomes in patients with gastric cancer. METHODS: We retrospectively reviewed 105 patients with pathologically proved gastric cancer who underwent pre-operative CT examinations and received radical gastrectomy with extended lymphadenectomy. Differences in CT characteristics between the LNM-positive and -negative groups were assessed by two observers. Binary logistic regression analysis was performed to determine the risk factors of lymph node metastasis in gastric cancer. Progression-free survival analysis was performed by Kaplan-Meier method. RESULTS: Two observers reached good inter-reader agreements in ctEMVI and ctN status with κ values of 0.711 and 0.751, respectively. The frequency of ctEMVI-positive status was 58.1% (61/105) in patients with gastric cancer. The LNM-positive group showed higher possibility of ctEMVI-positive status (81.7% vs 26.7%, p＜0.001), larger tumor volume (mean volume, 40.77 vs 22.09 mL, p＜0.001), poor tumor margin (45.0% vs 26.7% , p = 0.054) and high enhancement on arterial phase (43.3% vs 26.7%, p = 0.023) and venous phase (60.0% vs 44.4%, p = 0.048), than LNM-negative group. In multivariate analysis, ctEMVI status and tumor volume were identified as independent risk factors for lymph node metastasis with odds ratio (OR) of 9.804 (95% CI, 3.076－31.246; p＜0.001) and 1.030 (95% CI, 1.001－1.060; p = 0.044). CT-detected EMVI presented better diagnostic efficiency for lymph node metastasis than CT-defined N status, with sensitivity (81.7% vs 70.0%), specificity (73.3% vs 71.1%), accuracy (78.1% vs 70.5), PPV (80.3% vs 76.4%), and NPV (75.0% vs 64.0%), respectively. Kaplan-Meier curves showed that patients with positive ctEMVI findings has lower PFS rate than patients with negative ctEMVI findings (Log-rank test, p = 0.007). CONCLUSION: CT-detected EMVI was significantly associated with lymph node metastasis and progression free survival in patients with gastric cancer. Compared to CT-defined N status, ctEMVI provided superior diagnostic performance to predict pathologic Nstatus. ADVANCES IN KNOWLEDGE: Our study proved that CT-detected EMVI is a promising imaging marker to predict lymph node metastasis and poor prognosis, which may contribute to the precise evaluation of gastric cancer before surgery.

Acceptance of Online Medical Websites: An Empirical Study in China.

As a new type of public health service product, online medical websites (OMWs) are becoming quite popular. OMWs can address patients' basic medical problems remotely and give health guidance online. Compared to traditional hospitals, OMWs are more convenient and inexpensive, they can usually provide a better service for patients with poor medical conditions (especially in rural areas), and they also contribute to the rational distribution of medical resources. Therefore, key factors that affect patients' acceptance of OMWs must be identified to contribute to public health. By integrating perceived risk (PR) and the technology acceptance model (TAM), we proposed a modified TAM and clarified how PR and other factors affect patients' behavioral intention (BI) towards OMWs. A sample of 245 research participants in China took part in this study and the structural equation model (SEM) was used to test our hypotheses. The results revealed that perceived usefulness (PU) is a positive predictor of BI but has no significant effect on attitude (ATT), while perceived ease of use (PEOU) can affect BI through PU and attitude (ATT). Moreover, trust (TRU) was identified as a mediator of PR and PU/PEOU. Also, the doctor⁻patient relationship (DPR) was shown to moderate PR and TRU. In order to increase patients' BI, OMW providers need further innovations to improve patients' TRU and reduce their PR.

Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channels.

The noradrenergic neurons of the locus coeruleus (LC) are associated with various brain functions and psychiatric disorders, such as addiction and depression. It has been shown that neuropeptide galanin (GAL) inhibits neuronal excitability in LC, but the mechanisms remain unclear. In the present study, we investigated the ionic and signal transduction mechanisms underlying inhibitory effect of GAL on LC neurons using whole-cell patch clamp recording in rat brain slices. Bath application of GAL decreased the spontaneous firings and induced a dose-dependent hyperpolarization of LC neurons and this effect was attenuated by knockdown of Galr1, but not Galr2, confirming that mainly GALR1 mediates the inhibition effect of GAL. The inhibitory effect of GAL was also blocked by treatments of pertussis toxin (PTX), GTP-γ-s or GDP-ß-s, respectively, indicating that the functions of PTX sensitive Gi/o protein are required for GAL-induced hyperpolarization. Moreover, the blockers of GIRK (tertiapin-Q or SCH2 3390 hydrochloride) attenuated the GAL response while blocker of BK/SK/KATP channels or TASK-1/3 channels did not affect it significantly, suggesting that GIRK channels play an important role in GAL-induced hyperpolarization in LC neurons. Taken together, the inhibitory effect of GAL on LC neurons is mediated by GALR1 via PTX-sensitive Gi/o proteins, which activate GIRK channels.

A novel fluorescein-based "turn-on" probe for the detection of hydrazine and its application in living cells.

We constructed a novel probe for hydrazine detection based on ICT and PET mechanism. Phthalimide and acetyl ester groups were used as the recognition units. Addition of hydrazine produced a turn-on fluorescence at 525nm along with the fluorescent color change from dark to yellow. The probe could selectively detect hydrazine over other related interfering species. The detection limit of the probe for hydrazine was calculated to be 0.057µM which was lower than the EPA standard (0.320µM). Furthermore, the probe could also be applied for the imaging of hydrazine in living cells.

Activation of GSK-3 disrupts cholinergic homoeostasis in nucleus basalis of Meynert and frontal cortex of rats.

The cholinergic impairment is an early marker in Alzheimer's disease (AD), while the mechanisms are not fully understood. We investigated here the effects of glycogen synthase kinse-3 (GSK-3) activation on the cholinergic homoeostasis in nucleus basalis of Meynert (NBM) and frontal cortex, the cholinergic enriched regions. We activated GSK-3 by lateral ventricular infusion of wortmannin (WT) and GF-109203X (GFX), the inhibitors of phosphoinositol-3 kinase (PI3-K) and protein kinase C (PKC), respectively, and significantly decreased the acetylcholine (ACh) level via inhibiting choline acetyl transferase (ChAT) rather than regulating acetylcholinesterase (AChE). Neuronal axonal transport was disrupted and ChAT accumulation occurred in NBM and frontal cortex accompanied with hyperphosphorylation of tau and neurofilaments. Moreover, ChAT expression decreased in NBM attributing to cleavage of nuclear factor-κB/p100 into p52 for translocation into nucleus to lower ChAT mRNA level. The cholinergic dysfunction could be mimicked by overexpression of GSK-3 and rescued by simultaneous administration of LiCl or SB216763, inhibitors of GSK-3. Our data reveal the molecular mechanism that may underlie the cholinergic impairments in AD patients.

Analysis of Altered Micro RNA Expression Profiles in Focal Cortical Dysplasia IIB.

Focal cortical dysplasia type IIB is a commonly encountered subtype of developmental malformation of the cerebral cortex and is often associated with pharmacoresistant epilepsy. In this study, to investigate the molecular etiology of focal cortical dysplasia type IIB, the authors performed micro ribonucleic acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male, mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24 micro RNAs were differentially expressed in focal cortical dysplasia type IIB, and the microarray results were validated using quantitative real-time polymerase chain reaction (PCR). Then the putative target genes of the differentially expressed micro RNAs were identified by bioinformatics analysis. Moreover, biological significance of the target genes was evaluated by investigating the pathways in which the genes were enriched, and the Hippo signaling pathway was proposed to be highly related with the pathogenesis of focal cortical dysplasia type IIB.

[Prokaryotic Expression of Rv0757 Gene in Mycobacterium tuberculosis and the Effect of Its Coding Protein on the Function of Macrophage].

OBJECTIVE: To construct recombinant plasmid pET28a-Rv0757 with Mycobacterium tuberculosis (Mtb) Rv0757 gene, and to determine the effect of the protein of Rv0757 gene on ANA-1 cells. METHODS: We recombined the amplified Rv0757 gene into theprokaryotic plasmid pET28a (+). The expressed product was identified by SDS-PAGE and Western blot. Murine macrophages were treated with purified protein PhoP. Survived cells, lactic dehydrogenase (LDH), nitric oxide (NO), and cell apoptosis were detected after the treatment. RESULTS: We successfully constructed the recombinant plasmid pET28a-Rv0757. The target protein was confirmed by SDS-PAGE and Western blot. The protein had no significant effect on cell numbers and LDH activities in the culture supernatant, but it inhibited the release of NO and apoptosis of ANA-1 cells. CONCLUSION: pET28a-Rv0757 plasmid with prokaryotic expression was successfully constructed. The targetprotein has no toxicity on macrophages, but it can inhibit NO release and cell apoptosis of ANA-1.

Plasma galanin is a biomarker for severity of major depressive disorder.

OBJECTIVE: This study investigated the association between plasma galanin level and depression severity. METHODS: The severity of depression symptoms of 79 patients with major depressive disorder (MDD; 52 women and 27 men, 71 patients in onset, 8 in remission) was assessed using the 17-item Hamilton Depression Rating Scale. Venous fasting blood samples (5 mL) were taken from the 79 MDD patients, 35 healthy siblings, and 19 healthy controls, and plasma samples were prepared. Galanin levels in the plasma were measured by radioimmunoassay. RESULTS: Plasma galanin in MDD patients was significantly higher than that of remission patients, healthy siblings, or healthy controls (P < 0.05) There was no significant difference between the healthy sibling and healthy control groups (P = 0.924). Plasma galanin of remission patients was also significantly higher than that of healthy controls (P < 0.05). There was no significant correlation between age and galanin levels in the 79 patients (r = 0.053, P = 0.646), nor was there a correlation between age and galanin levels when patients were stratified by gender (P > 0.05). There was a significant positive correlation between plasma galanin levels and depression severity in women MDD patients (r = 0.329, df = 42, P = 0.020), but not in men patients. CONCLUSIONS: Plasma galanin levels may be an important biomarker for depression severity, especially in female patients.

Association of galanin and major depressive disorder in the Chinese Han population.

OBJECTIVE: This study aimed to investigate the association of galanin (GAL) gene and the development of depression in the Chinese Han population. METHODS: A total of 700 patients with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 673 healthy controls were used in this study. Ligase detection reactions were performed on 10 selected single nucleotide polymorphism (SNP) sites in the GAL gene. A series of statistical methods were carried out to investigate the correlation between the GAL gene SNP and the patient susceptibility to depression. RESULTS: The SNPs of rs694066 in the GAL gene showed a positive correlation with MDD. Compared with the healthy controls, lower frequency of G/G genotype and higher frequency of A/G genotype were observed in rs694066 in MDD patients, a lower frequency of G-allele and higher frequency of A-allele were observed in rs694066. These correlations were more pronounced in the 376 female patients and 360 female control subjects than in the 324 male patients and 313 healthy male subjects. CONCLUSIONS: This study investigated the relationship between the GAL gene SNP and the susceptibility to depression in the Chinese Han population. The findings clearly indicate that the GAL gene polymorphism is closely correlated to the incidence of depression in the Chinese Han female patients.

Lack of association between dendritic cell nuclear protein-1 gene and major depressive disorder in the Han Chinese population.

OBJECTIVES: Dendritic cell nuclear protein-1 (DCNP1) has been associated with major depressive disorder (MDD) based on analysis of a population of patients in the United Kingdom. In the present study we have investigated a possible role of DCNP in MDD in the Han Chinese population, including a meta-analysis of different ethnic populations. METHODS: Eight single nucleotide polymorphisms (SNPs) spanning the entire DCNP1 were carefully selected, genotyped and used for the SNP and haplotype analyses in 574 patients with MDD and 642 healthy controls. Considering the potential genetic association difference across different ethnic populations, we further conducted a meta-analysis for Chinese and European populations. RESULTS: rs10061623 showed initial association with MDD in females in the allele analysis (p-value: 0.043). However, this association did not remain significant after Bonferroni correction to adjust for multiple comparisons (corrected p-value: 0.344). Other single-marker and haplotype analyses did not reveal any significant differences between patients and controls. The SNP (rs12520799), positive in the original UK study, gave negative results in all our analyses. The meta-analysis results of rs12520799 also suggested possible negative association between this SNP and MDD in the Han Chinese population. CONCLUSIONS: In the Han Chinese population, common DCNP1 polymorphisms are unlikely to be important in the genetic susceptibility to MDD.

Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma.

AIM: To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1 (LINE-1), ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma (HCC) cells. METHODS: MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells. Cell proliferation inhibition and the IC50 were calculated by the Origin 8.0 software. Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes, including p53, p27, p15, Bcl-2, mdr, and p-gp. To corroborate the proliferation and anchor-independent growth results, the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF-1p on the apoptosis regulation. RESULTS: LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs (cisplatin and epirubicin) in HepG2 cells. The IC50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L. Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin. The IC50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L. Interestingly, down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel. The IC50 decreased from 35.90 nmol/L to 7.36 nmol/L. However, overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells. Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression. As a protein arrested in the nucleus, LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors. Indeed, LINE-1 ORF-1p promoted HepG2 cell proliferation, anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15, p21, p53, and Bcl-2 genes. CONCLUSION: LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs. By establishing novel roles and defining the mechanisms of LINE-1 ORF-1p in HCC chemotherapeutic drug resistance and cell proliferation regulation, this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.

Ultraviolet-visible light (UV-Vis)-reversible but fluorescence-irreversible chemosensor for copper in water and its application in living cells.

An ultraviolet-visible light (UV-Vis)-reversible but fluorescence-irreversible chemosensor was developed for the detection of copper. Coordination between the probe, 2-pyridylaldehyde fluorescein hydrazone (FHP), and Cu(2+) gave a reversible UV-Vis response, Storage of the probe-Cu complex resulted in hydrolytic cleavage of the N═C bond, which released the fluorophore (ring-opened fluorescein hydrazine) and gave irreversible fluorescence. Thus, FHP becomes a multifunctional chemosensor, and its reversibility can be controlled by the reaction time. Cu(2+) in living cells could be detected using FHP and general fluorescence methods.

Indicator approach to develop a chemosensor for the colorimetric sensing of thiol-containing water and its application for the thiol detection in plasma.

A strategy for the determination of the presence of thiol-containing amino acids was successfully established by simply assembling copper chloride and xylenol orange (3,3'-bis[N,N-bis(carboxymethyl)aminomethyl]-o-cresolsulfonephthalein trisodium salt; XO) in a 1 : 1 molar ratio in quasi-physiological water solution (pH 6.0). The copper(II)-XO ensemble was highly selective for thiol species such as cysteine, homocysteine, and glutathione without interference from other amino acids and could quantitatively detect thiol in the range from 10 to 200 µM with a linear relationship having an average molar absorbance constant of 6530 L mol(-1) cm(-1) in pure water. The whole recognition process for thiol gave rise to a rapid visual color change from purple-red to yellow which can be observed simultaneously with the naked-eye.