G protein-coupled receptor-mediated signaling of immunomodulation in tumor progression.

G protein-coupled receptors (GPCRs) are essential contributors to tumor growth and metastasis due to their roles in immune cell regulation. Therefore, GPCRs are potential targets for cancer immunotherapy. Here, we discuss the current understanding of the roles of GPCRs and their signaling pathways in tumor progression from an immunocellular perspective. Additionally, we focus on the roles of GPCRs in regulating immune checkpoint proteins involved in immune evasion. Finally, we review the progress of clinical trials of GPCR-targeted drugs for cancer treatment, which may be combined with immunotherapy to improve treatment efficacy. This expanded understanding of the role of GPCRs may shed light on the mechanisms underlying tumor progression and provide a novel perspective on cancer immunotherapy.

MicroRNA-144 Regulates Cardiomyocyte Proliferation and Apoptosis by Targeting TBX1 through the JAK2/STAT1 Pathway.

It is currently believed that the TBX1 gene is one of the core genes of congenital heart disease (CHD). However, there are few studies on the abnormal regulation of TBX1 gene expression. The purpose of this work was to investigate the role of miR-144 and TBX1 in cardiac development by studying the regulatory relationship and mechanism of miR-144 on TBX1/JAK2/STAT1 in cardiomyocytes. Cell proliferation was detected by MTT and clone formation assay and cell cycle and apoptosis by flow cytometry. The levels of miR-144 and TBX1 in H9c2 cells were assessed by qRT-PCR. Dual luciferase reporter assay was used to validate the direct targeting of TBX1 with miR-144. The protein expression levels of TBX1 and its downstream proteins were measured by Western blot analysis. miR-144 inhibited H9c2 cell proliferation by arresting cells in G1 phase. Furthermore, miR-144 induced H9c2 cell apoptosis and activated the JAK2/STAT1 signaling pathway. Bioinformatic predictions and luciferase reporter assay showed that miR-144 directly targets TBX1. Co-overexpression of miR-144 and TBX1 upregulated cell proliferation by accelerating G1 to S phase transition and downregulated cell apoptosis through inhibiting the JAK2/STAT1 signaling pathway. miR-144 acts as a proliferation inhibitor in cardiomyocytes via the TBX1/JAK2/STAT1 axis and is therefore a potential novel therapeutic target for CHD treatment.

Assessment of warfarin algorithms for hospitalized adults: searching for a safe dosing strategy.

This study evaluates three warfarin dosing algorithms (Kimmel, Dawson, High Dose ≥ 2.5 mg) for hospitalized older adults. A random selection of 250 patients with overshoots (INR ≥ 5 after 48 h of hospitalization) and 250 patients without overshoots were accessed from a database of 12,107 inpatients ≥ 65 years treated with chronic warfarin during hospitalization between January 1, 2014 and June 30, 2016. Algorithms were retrospectively applied to patients 2 days prior to overshoots in the overshoot group, and 2 days prior to the maximum INR reached after 48 h of hospitalization in the non-overshoot group. Patients were categorized as overdosed or not overdosed and compared using descriptive statistics. Logistic regression modeling determined predictors for overshoots. There was no significant difference between overdose and non-overdose groups for progressing to overshoots by the Kimmel (51.0% vs. 48.7%, p = 0.67) or Dawson (48.5 vs. 57.9%, p = 0.19) algorithms. The Low Dose Group (≤ 2.5 mg) was significantly more likely to experience an overshoot than the High Dose Group (56.6% vs. 45.5%, p = 0.04). The Low Dose Group was more likely to be older (81.4% vs. 71.1%, p = 0.02), female (63.5% vs. 49.8%, p = 0.02), weigh less (71.3 ± 21.9 vs. 79 ± 23.1, p = 0.002), and be prescribed amiodarone (16.6% vs. 8.1%, p = 0.01). While none of the algorithms predicted overshoots in logistic regression modeling, weight over 70 kg and black race remained protective. The High Dose Algorithm revealed that providers appropriately gave lower doses to patients at highest risk for warfarin sensitivity. Future studies are needed to investigate tools for inpatient warfarin dosing in older adults.

Quality metrics of warfarin initiation in hospitalized older adults.

Achieving therapeutic international normalized ratio (INRs) in warfarin naïve older adults can be complicated due to sensitivity factors. While multiple tools exist for warfarin initiation in the outpatient setting, there is a dearth of guidance for inpatient initiation. This study aims to: (1) describe a large health system's initiation warfarin quality metrics in older inpatients, defined by INR overshoots greater than or equal to 5.0; (2) identify intrinsic and extrinsic patient factors associated with overshoots; and (3) explore the association between inpatient overshoots and clinical outcomes. Data on inpatients ≥ 65 years initiated on warfarin 1/1/2014-6/30/2016 were extracted through retrospective chart review. The primary outcome was prevalence of overshoots (INR ≥ 5). Logistic regression modeling determined the risk factors for overshoots. Multivariate analysis was employed to associate overshoots with length of stay (LOS), bleeding, and mortality. Additional analysis of the impact of patient weight (kg) on overshoots was achieved through chi square analysis. Of 4556 inpatients initiated on warfarin, 8% experienced overshoots. Non-black race, peripheral vascular disease, chronic obstructive pulmonary disease (COPD), mild liver disease, low weight, and no statin use were found to be predictive of overshoots. Compared to the group without overshoots, the group with overshoots experienced a significantly increased LOS (13 days vs. 8 days, < 0.001), higher bleed rate (30.1% vs. 6.5%, adjusted OR 6.2, p < 0.001), and higher mortality rate (13.8% vs. 3.4%, adjusted OR 4.4, p < 0.001). Inpatient warfarin initiation was associated with frequent overshoots and poor outcomes. Future studies should focus on strategies to improve hospital warfarin initiation safety.

Segmentation of Online Ferrograph Images with Strong Interference Based on Uniform Discrete Curvelet Transformation.

Through real-time acquisition of the visual characteristics of wear debris in lube oil, an on-line visual ferrograph (OLVF) achieves online monitoring of equipment wear in practice. However, since a large number of bubbles can exist in lube oil and appear as a dynamically changing interference shadow in OLVF ferrograms, traditional algorithms may easily misidentify the interference shadow as wear debris, resulting in a large error in the extracted wear debris characteristic. Based on this possibility, a jam-proof uniform discrete curvelet transformation (UDCT)-based method for the binarization of wear debris images was proposed. Through multiscale analysis of the OLVF ferrograms using UDCT and nonlinear transformation of UDCT coefficients, low-frequency suppression and high-frequency denoising of wear debris images were conducted. Then, the Otsu algorithm was used to achieve binarization of wear debris images under strong interference influence.

A Wear Debris Segmentation Method for Direct Reflection Online Visual Ferrography.

Wear debris in lube oil was observed using a direct reflection online visual ferrograph (OLVF) to monitor the machine running condition and judge wear failure online. The existing research has mainly concentrated on extraction of wear debris concentration and size according to ferrograms under transmitted light. Reports on the segmentation algorithm of the wear debris ferrograms under reflected light are lacking. In this paper, a wear debris segmentation algorithm based on edge detection and contour classification is proposed. The optimal segmentation threshold is obtained by an adaptive canny algorithm, and the contour classification filling method is applied to overcome the problems of excessive brightness or darkness of some wear debris that is often neglected by traditional segmentation algorithms such as the Otsu and Kittler algorithms.

Measuring Functional Status in Hospitalized Older Adults Through Electronic Health Record Documentation.

OBJECTIVES: Hospitalization-associated disability affects up to 60% of older adults; however, standardized measures of function are not routinely used and documented. We sought to determine whether nursing documentation in electronic medical records can be used to determine mobility status and associated clinical outcomes. METHODS: A retrospective study of 2383 medical patients aged 75 years and older was conducted at a large academic tertiary hospital in New York. Mobility (low, intermediate, and high) was the primary variable of interest. Short-term clinical outcomes, including length of stay (LOS), discharge disposition, and readmissions, were the primary outcome variables. RESULTS: Average age and Charlson Comorbidity Index were 84.7 (range 74-107) and 6.46, respectively; 84.5% of patients were documented to have been ambulatory before admission. More than half (52.8%) of the subjects with in-hospital mortality were in the low mobility group (27.2 vs 0.27 vs 0, P < 0.0001). Low mobility was associated with increased LOS (7.42 vs 5.69 vs 4.14, P < 0.0001), discharge to a skilled nursing facility (39.36 vs 14.67 vs 1.91, P < 0.0001), and 30-day readmission (24.40 vs 16.67 vs 10.93, P < 0.0001). After controlling for demographics, ambulatory status before admission, and Charlson Comorbidity Index, low mobility was statistically significantly associated with increased LOS, discharge to a skilled nursing facility, and 30-day readmissions. CONCLUSIONS: The use of documented nursing observation may provide a practical way to systematically identify patients at risk for poor outcomes associated with low mobility to ultimately improve outcomes of hospitalized older adults.

Vascular permeability determined using multi-slice spiral CT perfusion can predict response to chemoradiotherapy in patients with advanced cervical squamous cell carcinoma
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AIM: This study aims to use multi-slice spiral computed tomography (CT) perfusion to investigate the predictive value of vascular permeability in determining the response of patients with advanced cervical squamous-cell carcinoma (CSCC) to chemoradiotherapy treatment. METHODS: 196 patients with advanced CSCC were recruited. Multi-slice spiral CT perfusion was performed before chemoradiotherapy, and perfusion parameters, such as blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS), were obtained. After treatment, patients were divided into a sensitive group and a resistant group. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive value of the perfusion parameters. The association of the perfusion parameters with the response of CSCC to chemoradiotherapy was analyzed using logistic regression analysis. RESULTS: Lesion size and treatment duration were remarkably different between the sensitive (n = 101) and resistant groups (n = 95) (both p < 0.05). Before chemoradiotherapy, the sensitive group had a significantly higher BV and PS than the resistant group (both p < 0.05). The logistic regression analysis showed that lesion size, BV, and PS are associated with the response of CSCC to chemoradiotherapy (all p < 0.05). The sensitivity and the specificity of BV and PS were 65.3% and 83.2% and 75.2% and 72.6%, respectively. CONCLUSION: BV and PS values determined using CT perfusion correlate with and predict the response to chemoradiotherapy in the treatment of advanced CSCC. Patients with smaller lesions require shorter periods of treatment.
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Reactive astrocytes secrete lcn2 to promote neuron death.

Glial reaction is a common feature of neurodegenerative diseases. Recent studies have suggested that reactive astrocytes gain neurotoxic properties, but exactly how reactive astrocytes contribute to neurotoxicity remains to be determined. Here, we identify lipocalin 2 (lcn2) as an inducible factor that is secreted by reactive astrocytes and that is selectively toxic to neurons. We show that lcn2 is induced in reactive astrocytes in transgenic rats with neuronal expression of mutant human TAR DNA-binding protein 43 (TDP-43) or RNA-binding protein fused in sarcoma (FUS). Therefore, lcn2 is induced in activated astrocytes in response to neurodegeneration, but its induction is independent of TDP-43 or FUS expression in astrocytes. We found that synthetic lcn2 is cytotoxic to primary neurons in a dose-dependent manner, but is innocuous to astrocytes, microglia, and oligodendrocytes. Lcn2 toxicity is increased in neurons that express a disease gene, such as mutant FUS or TDP-43. Conditioned medium from rat brain slice cultures with neuronal expression of mutant TDP-43 contains abundant lcn2 and is toxic to primary neurons as well as neurons in cultured brain slice from WT rats. Partial depletion of lcn2 by immunoprecipitation reduced conditioned medium-mediated neurotoxicity. Our data indicate that reactive astrocytes secrete lcn2, which is a potent neurotoxic mediator.

Oncogenic miR-23a in Pancreatic Ductal Adenocarcinogenesis Via Inhibiting APAF1.

BACKGROUND: miR-23a, which participates in invasion of pancreatic ductal adenocarcinoma cells into the mesothelial barrier, is a critical regulator in many cancers. It, however, is still unknown whether miR-23a regulates pancreatic cell proliferation and apoptosis or not. AIMS: We sought to investigate the role of miR-23a in regulation of pancreatic cell proliferation and apoptosis. METHODS: miRNA, mRNA, and protein expressions were determined by qRT-PCR and Western blot, respectively. Dual-luciferase reporter assay was used in detection for binding ability of miR-23a to APAF1. Ectopic miR-23a and APAF 1 were introduced to pancreatic cells, and their roles in proliferation and apoptosis were detected by MTT, colony formation, and apoptosis assays, respectively. RESULTS: Up-regulation of miR-23a and down-regulation of APAF 1 were found in pancreatic ductal cancer, respectively. miR-23a significantly inhibited the luciferase activity by targeting APAF 1 3'UTR. Ectopic miR-23a significantly suppressed the APAF 1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. Furthermore, miR-23a inhibitor and exogenous APAF 1 could recover the effects. CONCLUSIONS: It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer.

Chrebp regulates the transcriptional activity of androgen receptor in prostate cancer.

Androgen receptor (AR), a member of nuclear hormone receptor, plays an essential role in the initiation and progression of prostate cancer (PCa). In the present study, by way of immunoprecipitation followed by mass spectrometry (IP/MS) system, we found that carbohydrate-responsive element-binding protein (Chrebp), a glucose sensor in normal and cancer cells, interacted with AR in LNCaP cells. The interaction was further confirmed by coimmunoprecipitation analysis. Besides, Chrebp is required for the optimal transcriptional activity of AR in promoting the transcription of the prostate-specific antigen (PSA) promoter and messenger RNA (mRNA) expression. Consistently, knockdown of Chrebp using small interfering RNA (siRNA) in LNCaP cells reduced endogenous PSA levels. Together, our study demonstrates that Chrebp interacts with AR and regulates its transcriptional activity.

MicroRNA-27a promotes proliferation and suppresses apoptosis by targeting PLK2 in laryngeal carcinoma.

BACKGROUND: miRNA-27a has been confirmed as an important regulator in carcinogenesis and other pathological processes. Whether and how it plays a role in the laryngeal carcinoma is unknown. METHODS: Mature miRNA-27a expression in laryngeal cancer was detected by qRT-PCR. Gain-of-function studies using mature miR-27a were performed to investigate cell proliferation and apoptosis in the Hep2 cells. In silico database analysis and luciferase reporter assay were applied to predict and validate the direct target, respectively. Loss-of-function assays were performed to investigate the functional significance of the miR-27a target gene. qRT-PCR and Western blot were used to evaluate mRNA and protein levels of the target, respectively. RESULTS: miR-27a was significantly up-regulated in the laryngeal tumor tissues compared to the adjacent non-tumor tissues. In silico database analysis result revealed that PLK2 is a potential target of miR-27a. luciferase reporter assay result showed the direct inhibition of miR-27a on PLK2-3'UTR. In the cases with miR-27a up-regulation, PLK2 protein expression level was significantly lower in cancer tissues than that in the adjacent non-tumor tissues, which showed a negative correlation with miR-27a expression level. Both miR-27a and knockdown of PLK2 caused the increase of the cell viability and colony formation and inhibition of the late apoptosis in the Hep2 cell lines. Moreover, miR-27a but not PLK2 also repressed the early apoptosis in the Hep2 cells. Additionally, no alteration of the Hep2 cell cycle induced by miR-27a was detected. CONCLUSIONS: miR-27a acts as an oncogene in laryngeal squamous cell carcinoma through down-regulation of PLK2 and may provide a novel clue into the potential mechanism of LSCC oncogenesis or serve as a useful biomarker in diagnosis and therapy in laryngeal cancer.

[Long term survival analysis of primary hepatocarcinoma patients received transcatheter arterial chemoembolization plus chemotherapy after radical resection].

OBJECTIVE: To evaluate the survival of hepatocellular carcinoma (HCC) patients received prophylactic use of transcatheter arterial chemoembolization (TACE) after radical resection. METHODS: One hundred and forty-three cases of HCC from Ningbo No.2 Hospital were divided into intervention prevention group, chemotherapy prevention group and comprehensive prevention group according to different methods of HCC prevention. All patients were followed-up for more than 5 years after TACE, chemotherapy (FOLPOX4) or TACE+ FOLPOX4. Cox regression model of multiple factors analysis was used for analyzing impact factors on HCC prognosis. Survival rate was compared with Kaplan-meier method. RESULTS: Alpha-fetoprotein (AFP) was negatively correlated with the survival time of patients, as an independent risk factor with the regression coefficient of 0.01 and the relative risk of 1.00. Prevention of postoperative increased survival time of patients with HCC, which was a protective factor. The regression coefficient for comprehensive prevention was -2.37 and the relative risk was 0.07, the weight of comprehensive prevention on lifetime was higher than that of other two prevention methods, followed by TACE prevention group. One-year, 2-year, 3-year cumulative survival rates in comprehensive prevention group were 78.35%， 69.16%， 24.43%， that in TACE prevention group were 76.87%， 62.48%， 24.72%， and that in chemotherapy prevention group were 62.23%， 43.22%， 19.54%， respectively. CONCLUSION: AFP was negative correlation with the survival time of postoperative HCC patients, monitored which of postoperative HCC patients can provide a reference for effect and prognosis of surgery. Application of TACE in HCC patients with postoperative effective in reducing mortality, which prolong the survival time of HCC patients might be extended further by combined chemotherapy based on its own advantages and disadvantages.

Conservation tillage facilitates the accumulation of soil organic carbon fractions by affecting the microbial community in an eolian sandy soil.

Conservation tillage (CT) is an important agronomic measure that facilitates soil organic carbon (SOC) accumulation by reducing soil disturbance and plant residue mulching, thus increasing crop yields, improving soil fertility and achieving C neutrality. However, our understanding of the microbial mechanism underlying SOC fraction accumulation under different tillage practices is still lacking. Here, a 6-year in situ field experiment was carried out to explore the effects of CT and traditional tillage (CK) practices on SOC fractions in an eolian sandy soil. Compared with CK, CT increased the particulate OC (POC) content in the 0-30 cm soil layer and the mineral-associated OC (MAOC) content in the 0-20 cm soil layer. Moreover, tillage type and soil depth had significant influences on the bacterial, fungal and protistan community compositions and structures. The co-occurrence network was divided into 4 ecological modules, and module 1 exhibited significant correlations with the POC and MOC contents. After determining their topological roles, we identified the keystone taxa in the network. The results indicated that the most common bacterial taxa may result in SOC loss due to low C use efficiency, while specific fungal (Cephalotrichum) and protistan (Cercozoa) species could facilitate SOC fraction accumulation by promoting macroaggregate formation and predation. Therefore, the increase in keystone fungi and protists, as well as the reduction in bacteria, drove module 1 community function, which in turn promoted SOC sequestration under CT. These results strengthen our understanding of microbial functions in the accrual of SOC fractions, which contributes to the development of conservation agriculture on the Northeast China Plain.

Mutations and down-regulation of CDX1 in children with anorectal malformations.

BACKGROUND: Anorectal malformations (ARMs) represent a variety of congenital disorders that involve abnormal termination of the anorectum. This study was to reveal relation between CDX1 and human ARMs phenotypes. METHODS: 108 Chinese patients and 120 Chinese controls were included in this study. We analyzed the relation between two by PCR, qRT-PCR, western blot and immunofluorescence. RESULTS: Four heterozygous mutations in CDX1 gene were identified in ARMs patients (3.7%, 4/108), no found in controls. CDX1 protein expression was significantly decreased in the ARMs compared with the control anorectum. All samples analyzed in ARMs group exhibited down-regulated CDX1 mRNA expression in comparison to matched normal group, demonstrated significant differences statistically. CONCLUSION: The findings represented the relation between CDX1 mutations and CDX1 genotype. Furthermore, it was suggested that the downregulation of CDX1 might be related to the development of ARMs.

Intracerebral hematoma extends via perivascular spaces and perineurium.

Intracerebral hemorrhage (ICH) is a devastating disorder associated with high morbidity and mortality. ICH results in the formation of hematoma that affects not only the primary site of injury but also the remote regions. In fact, hematoma can extend via perivascular spaces (also called Virchow-Robin spaces, VRS) and perineurium in an animal model of ICH. In the present study, we used magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) to investigate the characteristics of the perivascular and perineural extensions of hematomas in patients with ICH. A total of 20 ICH patients without secondary subarachnoid and secondary intraventricular hemorrhages were recruited. Brain MRI scans, including SWI, T1, and T2-weighted images, were performed between 17 h to 7 days after the onset of ICH. MRI with SWI revealed that paramagnetic substances spread along the VRS or the perineurium. Such distribution could cause the formation of cerebral microbleeds (CMBs). However, the distribution of remote hemorrhagic lesions varied, depending on the size and location of the original hematoma. The unenhanced CT scans of the 20 patients did not show any hyperdensity around the blood vessels and nerve tracts outside the hematoma. These results indicate the perivascular and perineural extensions of hematomas in patients with ICH, which is formed by the leakage of the original hematoma via the VRS or perineurium. We also provide a new explanation for the series of pathological processes involved in ICH, including the remote effects of hematoma and the formation of CMBs in patients with ICH.

Optimized extraction technology of glutathione from 'Haidao 86' germ rice by response surface methodology.

Glutathione is an important functional component of 'Haidao 86', which has many important physiological functions in organisms and is widely used in medicine and other industries. In this study, the effects of four extraction methods (hot water extraction, formic acid extraction, ethanol extraction, and sulfuric acid extraction) on the yield of glutathione in 'Haidao 86' germ powders were studied by high-performance liquid chromatography, and the yield of glutathione in hot water extraction was the highest. The effects of material-liquid ratio, temperature, pH, and time on the extraction rate of glutathione from 'Haidao 86' were investigated by single-factor experiment and Box-Behnken combined experiment. The results showed that the order of influence on GSH yield was pH, temperature, material-liquid ratio, and time, and the interaction of extraction time and pH had a significant influence on glutathione yield of 'Haidao 86' germ powders. The optimum parameters for hot water extraction of glutathione from 'Haidao 86' germ powders were determined as follows: material-liquid ratio of 1:12, pH value of 2.8, temperature of 84.9°C, time of 14 min, and the extraction rate of glutathione was 139.68 mg/100 g. It provided the scientific proof for the development and industrial production of functional products of 'Haidao 86'.

Promoter hypermethylation-induced transcriptional down-regulation of the gene MYCT1 in laryngeal squamous cell carcinoma.

BACKGROUND: MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated. METHODS: Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). RESULTS: The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (-695 to -692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (-852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3-MYCT1 (-852/+12), while the luciferase activity from wild transfectants pGL3-MYCT1 (-852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (-695 to -692) site prevented c-Myc from binding of the site and demethylation treatment of the 5' flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01). CONCLUSION: In summary, this study concluded that hypermethylation contributed to the transcriptional down-regulation of MYCT1 and could inhibit cancer cell differentiation in LSCC. DNA methylation of the CGCG site (-695 to -692) of MYCT1 altered the promoter activity by interfering with its binding to c-Myc in LSCC. Epigenetic therapy of reactivating MYCT1 by 5-aza should be further evaluated in clinical trails of LSCC.

Fluoxetine promotes remission in acute experimental autoimmune encephalomyelitis in rats.

OBJECTIVE: This study was carried out to clarify the effects of the antidepressant fluoxetine, a selective serotonin reuptake inhibitor, for its potential use in autoimmune diseases like multiple sclerosis in a rat model of experimental autoimmune encephalomyelitis (EAE). METHODS: The rat EAE model was induced by subcutaneous injection of guinea pig spinal cord homogenate. Rats received fluoxetine via daily intragastric administration, starting 2 weeks prior to immune induction (fluoxetine pretreatment). Clinical scores and pathological changes in EAE rats were analyzed. Changes in serum cytokine levels were assessed by ELISA. RESULTS: Fluoxetine pretreatment significantly promoted remission in EAE. Histologically, fluoxetine-induced neuroprotection was accompanied by reductions in inflammatory foci and in the degree of demyelination in the spinal cord of EAE rats. The increase in serum IFN-γ in the EAE model was also suppressed by fluoxetine administration. CONCLUSIONS: These findings suggest that the prophylactic use of fluoxetine can relieve symptoms during remission in the acute EAE model, and these neuroprotective effects are associated with its anti-inflammatory effects.

Diaqua-bis-{3-[4-(1H-imidazol-1-yl)phenyl]-5-(pyridin-2-yl-κN)-1H-1,2,4-triazol-1-ido-κN(1)}zinc.

The centrosymmetric mol-ecule of the title compound, [Zn(C(16)H(11)N(6))(2)(H(2)O)(2)], contains one Zn(2+) ion located on a center of symmetry, two 3-[4-(1H-imidazol-1-yl)phen-yl]-5-(pyridin-2-yl)-1H-1,2,4-triazol-1-ide (Ippyt) ligands and two coordinating water mol-ecules. The Zn(II) ion is six-coordinated in a distorted octa-hedral coordination geometry by four N atoms from two Ippyt ligands and by two O atoms from two water mol-ecules. Adjacent units are inter-connected though O-H⋯N hydrogen bonds, forming a three-dimensional network.