[Effects of pre-electroacupuncture on blood pressure and cardiac function in high-salt-induced hypertension rats].

OBJECTIVE: To observe the effects of pre-electroacupuncture at "Taichong"(LR3), "Neiguan"(PC6) and "Waiguan"(TE5) on blood pressure and cardiac function of high-salt-induced hypertension rats, so as to explore the possible mechanism of pre-electroacupuncture in improving hypertension. METHODS: Twenty-four SD rats were randomly divided into control group, high-salt group and pre-electroacupuncture group, with 8 rats in each group. The hypertension model was established by feeding high-salt diet for 7 weeks. In the pre-electroacupuncture group, rats received electroacupuncture intervention at bilate-ral LR3, PC6 and TE5 (2 Hz/15 Hz, 2 mA) for 30 min, once a day, from the first day of modeling, for a total of 7 weeks. The blood pressure of rats was monitored by caudal artery noninvasive blood pressure measurement technique before and at the 1st, 3rd, 5th and 7th week of modeling. At the 8th week of the experiment, left ventricular catheterization was performed and biological signal acquisition system was used to detect left ventricular hemodynamics indexes and analyze left ventricular function, the car-diac mass ratio was measured to evaluate the degree of myocardial hypertrophy. The mRNA expressions of atrial natriuretic peptide(ANP), myosin heavy chain 7(MYH7), α-smooth muscle actin(α-SMA), interleukin(IL)-1ß, and IL-6 of myocardial tissues were detected by quantitative real-time PCR. Sirius red staining was used to observe the degree of myocardial fibrosis. RESULTS: Compared with the control group, systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular end-diastolic pressure (LVEDP), cardiac mass ratio，and the mRNA expressions of ANP, MYH7, α-SMA, IL-1ß, and IL-6, and sirius red staining area of myocardium were all significantly increased(P<0.01,P<0.05)，maximal rate of rise and descent of left ventricular pressure(LVP±dP/dtmax) were decreased (P<0.05,P<0.01) in the high-salt group. Compared with the high-salt group, rats in the pre-electroacupuncture group had lower systolic blood pressure, diastolic blood pressure, mean arterial pressure, LVEDP，cardiac mass ratio，higher LVP±dP/dtmax,down-regulated mRNA expressions of ANP, MYH7, α-SMA, IL-1ß, IL-6, and smaller area of sirius red staining(P<0.05, P<0.01). CONCLUSION: Pre-electroacupuncture tends to lower blood pressure, improve cardiac function and reduce myocardial fibrosis in high-salt-induced hypertension rats, which may be associated with inhibiting inflammatory response.

Interactions between the gut micro-community and transcriptome of Culex pipiens pallens under low-temperature stress.

BACKGROUND: Culex pipiens pallens (Diptera: Culicidae) can survive at low temperature for long periods. Understanding the effects of low-temperature stress on the gut microflora and gene expression levels in Cx. pipiens pallens, as well as their correlation, will contribute to the study of the overwintering mechanism of Cx. pipiens pallens. METHODS: The gut bacteria were removed by antibiotic treatment, and the survival of Cx. pipiens pallens under low-temperature stress was observed and compared with the control group. Then, full-length 16S rRNA sequencing and the Illumina HiSeq X Ten sequencing platform were used to evaluate the gut microflora and gene expression levels in Cx. pipiens pallens under low-temperature stress. RESULTS: Under the low-temperature stress of 7 °C, the median survival time of Cx. pipiens pallens in the antibiotic treatment group was significantly shortened by approximately 70% compared to that in the control group. The species diversity index (Shannon, Simpson, Ace, Chao1) of Cx. pipiens pallens decreased under low-temperature stress (7 °C). Non-metric multidimensional scaling (NMDS) analysis divided all the gut samples into two groups: control group and treatment group. Pseudomonas was the dominant taxon identified in the control group, followed by Elizabethkingia and Dyadobacter; in the treatment group, Pseudomonas was the dominant taxon, followed by Aeromonas and Comamonas. Of the 2417 differentially expressed genes (DEGs), 1316 were upregulated, and 1101 were downregulated. Functional GO terms were enriched in 23 biological processes, 20 cellular components and 21 molecular functions. KEGG annotation results showed that most of these genes were related to energy metabolism-related pathways. The results of Pearson's correlation analysis showed a significant correlation between the gut microcommunity at the genus level and several DEGs. CONCLUSIONS: These results suggest that the mechanism of adaptation of Cx. pipiens pallens to low-temperature stress may be the result of interactions between the gut bacterial community and transcriptome.

The Effect of Nursing Management of Patients Undergoing Interventional Therapy for Liver Cancer Compared with Standard Care on Patient-Reported Outcomes.

BACKGROUND: To investigate the efficacy of individualized symptom management based on patients' self-reports during interventional therapy (IT) for liver cancer. METHODS: Patients with liver cancer who recieved IT from April to August 2019 were assigned to either the intervention (n=70) or control group (n=70). The control group received routine nursing care and the intervention group received a nursing management program. The severity of specific symptoms, as measured by the Karnofsky Performance Scale (KPS), and satisfaction with nursing care, were analyzed. RESULTS: Compared to the control group, patients given individualized management experienced significantly less severe pain, nausea, anxiety, and fatigue (p < .05). The scores for KPS and satisfaction with care were both significantly improved in the intervention group than in the control group (p < .05). CONCLUSION: This high-quality nursing management program predicated on patients' self-reports is worthy of clinical application and popular adoption.

Comparison of Clinical Efficacy and Safety of Metformin Sustained-Release Tablet (II) (Dulening) and Metformin Tablet (Glucophage) in Treatment of Type 2 Diabetes Mellitus.

Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism.

The hippocampus is one of two niches in the mammalian brain with persistent neurogenesis into adulthood. The neurogenic capacity of hippocampal neural stem cells (NSCs) declines with age, but the molecular mechanisms of this process remain unknown. In this study, we find that fibroblast growth factor 13 (FGF13) is essential for the post-natal neurogenesis in mouse hippocampus, and FGF13 deficiency impairs learning and memory. In particular, we find that FGF13A, the nuclear isoform of FGF13, is involved in the maintenance of NSCs and the suppression of neuronal differentiation during post-natal hippocampal development. Furthermore, we find that FGF13A interacts with ARID1B, a unit of Brahma-associated factor chromatin remodeling complex, and suppresses the expression of neuron differentiation-associated genes through chromatin modification. Our results suggest that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in post-natal hippocampus, revealing an epigenomic regulatory function of FGFs in neurogenesis.

Single-Cell Isotope Dilution Analysis with LA-ICP-MS: A New Approach for Quantification of Nanoparticles in Single Cells.

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is an emerging method for the analysis of metal nanoparticles (NPs) in single cells. However, two main obstacles, low analytical throughput and lack of commercial reference materials, need to be overcome. In this work, we demonstrated the principles of a new approach termed "single-cell isotope dilution analysis" (SCIDA) to remove the two obstacles. For a proof of concept, macrophage cells were chosen as a model to study the uptake of silver NPs (AgNPs) at a single-cell level. Single cells exposed to AgNPs were placed in an array by a microfluidic technique; each cell in the array was precisely dispensed with a known picoliter droplet of an enriched isotope solution with a commercial inkjet printer; accurate quantification of AgNPs in single cells was done by using isotope dilution LA-ICP-MS. The average Ag mass of 1100 single cells, 396 ± 219 fg Ag per cell, was in good accord with the average of the population of cells determined by solution ICP-MS analysis. The detection limit was 0.2 fg Ag per cell. The SCIDA approach is expected to be widely applied for the study of cell-NP interactions and biological effects of NPs at the single-cell level.

Antitumor Activity and Mechanism Study of Riluzole and Its Derivatives.

To explore novel antitumor agents with high efficiency and low toxicity, riluzole alkyl derivatives (4a-4i) were synthesized. Their anti-proliferative activities against HeLa, HepG2, SP2/0, and MCF-7 cancer cell lines were assessed by the CCK-8 assay and compared with human normal liver (LO2) cells. Most of them showed potent cytotoxic effects against four human tumor cell lines and low toxic to LO2 cells. In particular, 2-(N-ethylamine)-6-trifluoromethoxy- benzothiazole (4a) showed a IC50 value of 7.76 µmol/L in HeLa cells and was found to be nontoxic to LO2 cells up to 65 µmol/L. Furthermore, flow cytometry indicated that 4a could induce remarkable early apoptosis and G2/M cell cycle arrest in HeLa cells. It also impaired the migration ability of HeLa cells in wound healing assays. Western blot results demonstrated that 4a suppressed Bcl-2 protein expression but increased the level of Bax in HeLa cells, and elevated the Bax/Bcl-2 expression ratio. These new findings suggest that 4a exhibited beneficially anti-cervical cancer effect on HeLa cells by inducing HeLa cell apoptosis.

Factors associated with appendicular skeletal muscle mass among male Chinese patients with stable chronic obstructive pulmonary disease: A hospital-based cross-sectional study.

Limbs muscle wasting is a common disorder in patients with chronic obstructive pulmonary disease (COPD) that limits daily activities and exercise intolerance, especially in males. The present study aimed to estimate the prevalence of appendicular skeletal muscle mass (ASM) in male patients with stable COPD. In addition, factors associated with parameters of ASM were also investigated.We recruited 116 male patients with stable COPD from the outpatient clinic between September 2016 and December 2017. For each patient, we obtained demographic characteristics and measured post-bronchodilator forced expiratory volume in 1 second, symptoms, exacerbations history, and ASM. ASM was defined as the sum of the muscle masses of the 4 limbs.Appendicular skeletal muscle mass index (ASMI) in male patients with stable COPD was 8.2 ±â€Š0.9 kg/m, and the prevalence of low skeletal muscle mass was 7.8% (9 of 116 patients). Multiple linear-regression analysis showed that body mass index, occupation, fat-free mass index, and the modified medical research council scale were significantly correlated with ASMI. Compared with nonexercise group, lower limb muscle mass and ASM were significantly improved in physical exercise group.Underweight, retirement, fat-free mass depletion, and severe dyspnea are all risk factors for ASM in male patients with stable COPD. Our findings also justify the importance of exercise training in improving ASM.

Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus.

Intestinal dysbiosis is implicated in Systemic Lupus Erythematosus (SLE). However, the evidence of gut microbiome changes in SLE is limited, and the association of changed gut microbiome with the activity of SLE, as well as its functional relevance with SLE still remains unknown. Here, we sequenced 16S rRNA amplicon on fecal samples from 40 SLE patients (19 active patients, 21 remissive patients), 20 disease controls (Rheumatoid Arthritis (RA) patients), and 22 healthy controls (HCs), and investigated the association of functional categories with taxonomic composition by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). We demonstrated SLE patients, particularly the active patients, had significant dysbiosis in gut microbiota with reduced bacterial diversity and biased community constitutions. Amongst the disordered microbiota, the genera Streptococcus, Campylobacter, Veillonella, the species anginosus and dispar, were positively correlated with lupus activity, while the genus Bifidobacterium was negatively associated with the disease activity. PICRUSt analysis showed metabolic pathways were different between SLE and HCs, and also between active and remissive SLE patients. Moreover, we revealed that a random forest model could distinguish SLE from RA and HCs (area under the curve (AUC) = 0.792), and another random forest model could well predict the activity of SLE patients (AUC = 0.811). In summary, SLE patients, especially the active patients, show an apparent dysbiosis in gut microbiota and its related metabolic pathways. Amongst the disordered microflora, four genera and two species are associated with lupus activity. Furthermore, the random forest models are able to diagnose SLE and predict disease activity.

NLRP3 in human glioma is correlated with increased WHO grade, and regulates cellular proliferation, apoptosis and metastasis via epithelial-mesenchymal transition and the PTEN/AKT signaling pathway.

Glioma is the most prevalent and fatal primary tumor of the central nervous system in adults, while the development of effective therapeutic strategies in clinical practice remain a challenge. Nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) has been reported to be associated with tumorigenesis and progression; however, its expression and function in human glioma remain unclear. The present study was designed to explore the biological role and potential mechanism of NLRP3 in human glioma. The results demonstrated that overexpression of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase­1 and interleukin (IL)­1ß protein in human glioma tissues were significantly correlated with higher World Health Organization grades. The in vitro biological experiments demonstrated that NLRP3 downregulation significantly inhibited the proliferation, migration and invasion, and promoted the apoptosis of SHG44 and A172 glioma cell lines. Furthermore, western blot assays revealed that the downregulation of NLRP3 significantly reduced the expression of ASC, caspase­1 and IL­1ß protein. Furthermore, NLRP3 knockdown caused the inhibition of epithelial-mesenchymal transition (EMT), and inhibited the phosphorylation of AKT serine/threonine kinase (AKT) and phosphorylation of phosphatase and tensin homolog (PTEN). Consistently, the upregulation of NLRP3 significantly increased the expression of ASC, caspase­1, IL­1ß and phosphorylated-PTEN, promoted proliferation, migration, invasion and EMT, inhibited apoptosis, and activated the AKT signaling pathway. The data of the present study indicate that NLRP3 affects human glioma progression and metastasis through multiple pathways, including EMT and PTEN/AKT signaling pathway regulation, enhanced inflammasome activation, and undefined inflammasome-independent mechanisms. Understanding the biological effects of NLRP3 in human glioma and the underlying mechanisms may offer novel insights for the development of glioma clinical therapeutic strategies.

AP-1 confers resistance to anti-cancer therapy by activating XIAP.

The underlying cause of treatment failure in many cancer patients is intrinsic and acquired resistance to chemotherapy. Recently, histone deacetylase (HDAC) inhibitors have developed into a promising cancer treatment. However, resistance mechanism induced by HDAC inhibitors remains largely unknown. Here we report that a HDAC inhibitor, JNJ-2648158 induced transcription of XIAP by activating AP-1 expression, which conferring resistance to chemotherapeutics. Our results showed that high expression of c-Fos caused by HDAC inhibitor promoted AP-1 formation during acquired resistance towards chemo-drugs, indicating an extremely poor clinical outcome in breast cancers and liver cancers. Our study reveals a novel regulatory mechanism towards chemo-drug resistance, and suggests that XIAP may serve as a potential therapeutic target in those chemo-resistant cancer cells.

Impact of Volume Management on Volume Overload and Rehospitalization in CAPD Patients.

Heart failure due to volume overload is a major reason for rehospitalization in continuous ambulatory peritoneal dialysis patients. Strict volume control provides better cardiac functions and blood pressure in this population. Volume management, which is a volume control strategy, may decrease volume overload and related complications. Using a quasi-experimental design, 66 continuous ambulatory peritoneal dialysis patients were randomly assigned to the intervention group ( n = 34) and control group ( n = 32). The patients were followed up for 6 months with scheduled clinic and/or telephone visits; the intervention group adopted volume management strategy, while the control group adopted conventional care. Volume overload and cardiac function were compared between the two groups at the baseline and at 6 months. At Month 6, the intervention group resulted in significant improvement in volume overloaded status, cardiac function, and volume-overload-related rehospitalization. Volume management strategy allows for better control of volume overload and is associated with fewer volume-related readmissions.

Empirically derived dietary patterns and ovarian cancer risk: a meta-analysis.

Dietary patterns, which reflect overall diet and possible nutrient and food interactions, have been reported to be related to ovarian cancer (OC) risk. However, studies on the relationship between dietary patterns and OC risk have been inconsistent. Thus, we carried out a systematic meta-analysis to assess the relationship between dietary patterns and the risk of OC. Relevant studies are identified by searching the Medline and Embase electronic databases up to December 2016. The Cochrane Q statistic and the I statistical were used to evaluate heterogeneity. A total of 22 studies fulfilled the inclusion criteria and were included in this meta-analysis. There was evidence of a decreased risk for OC in the highest versus the lowest categories of healthy dietary pattern [odds ratio (OR)=0.86; 95% confidence interval (CI): 0.74-0.99; P=0.04]. An increased risk of OC was shown for the highest versus the lowest category of a western-style dietary pattern (OR=1.19; 95% CI: 1.01-1.41; P=0.04). No significant association with OC risk was observed in the highest versus the lowest category of a heavy drinking pattern (OR=0.89; 95% CI: 0.67-1.19; P=0.42). The results of this meta-analysis suggest that a healthy dietary pattern is associated with reduced risk for OC and a western-style dietary pattern is associated with an increased risk of OC. Further studies are needed to confirm our results.

Epidemiological analysis of 133 malaria cases in Shanxian county, Shandong Province, China.

OBJECTIVE: To conduct an analysis of the epidemiological changes in malaria that have occurred in Shanxian county from 2002 to 2016. METHODS: A retrospective study was conducted and data were collected from web-based reporting system to explore the epidemiological characteristics in Shanxian county from 2002 to 2016. All individual case information was obtained from village malaria servicers organized by the local Shandong Institute of Parasitic Diseases. RESULTS: A total of 133 cases were identified as malaria in Shanxian county during this period, including 124 indigenous cases (93.2%) and 9 imported cases (6.8%). The 124 indigenous malaria cases were infected with Plasmodium vivax (P. vivax), whereas 7 of the 9 confirmed imported cases were infected with Plasmodium falciparum (P. falciparum), 1 was infected with Plasmodium ovale (P. ovale) and 1 patient was infected with P. falciparum mixed with P. vivax. The total number of malaria cases included 86 males (64.7%) and 47 females (35.3%). Age of the patients ranged from 1 to 83 years, although most (64.7%) infections occurred in the 21-to 60-year-old age group. Remarkably, 117 of the total malaria cases (98.0%) were reported from 2006 to 2011. The epidemic season was from June to October, with the peak occurring yearly from July to September. The most common occupation of the infected patients was farmer. In total, 58.1% of the cases occurred in 3 townships, namely, Fugang, Huanggang and Caozhuang. CONCLUSIONS: In Shanxian county, the local malaria incidence experienced an emerge-peak-control-eliminate status. However, due to the numbers of migrant labourers returning from Africa, imported cases were continuous and presented an increasing annual trend, which became a non-negligible and a significant impediment for malaria elimination. Therefore, the need to eliminate instances of malaria reintroduction to receptive malaria-free areas should drive strategies to align with the epidemiological changes.

Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract.

Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.

Epidermal growth factor and tumor necrosis factor α cooperatively promote the motility of hepatocellular carcinoma cell lines via synergistic induction of fibronectin by NF-κB/p65.

BACKGROUND: The interaction between hepatocellular carcinoma (HCC) cells and their microenvironment plays a fundamental role in tumor metastasis. The HCC microenvironment is rich in epidermal growth factor (EGF) and tumor necrosis factor α (TNFα), which may cooperatively, rather than individually, interact with tumor cells to influence their biological behavior. METHODS: Immunohistochemistry was performed to study the expression of EGF and TNFα in HCCs. Western blotting, immunofluorescence, qRT-PCR, wound healing scratch and invasion assay, and chromatin immunoprecipitation assays were used to study the combined roles of EGF and TNFα in the motility of HCC cells in vitro. RESULTS: We demonstrated that both EGF and TNFα were highly expressed in HCCs, and HCCs with higher expression of both EGF and TNFα were more frequently rated as high-grade tumors. In vitro, EGF and TNFα cooperatively promoted the motility of HCC cells mainly via synergistic induction of an extracellular matrix glycoprotein fibronectin (FN). Mechanistically, EGF and TNFα jointly increased the nuclear translocation and PKC mediated phosphorylation of NF-κB/p65 which could bind to the -356bp to -259bp fragment of the FN promoter, leading to a markedly increased activity of the FN promoter in HCC cells. CONCLUSIONS: HCCs with higher expression of both EGF and TNFα were more frequently rated as high-grade tumors. EGF and TNFα cooperatively promoted the motility of HCC cells mainly through NF-κB/p65 mediated synergistic induction of FN in vitro. GENERAL SIGNIFICANCE: These findings highlight the crosstalk between EGF and TNFα in promoting HCC, and provide potential targets for HCC prevention and treatment.

The TGF-ß-induced up-regulation of NKG2DLs requires AKT/GSK-3ß-mediated stabilization of SP1.

Natural killer (NK) cells play an important role in preventing cancer development. NK group 2 member D (NKG2D) is an activating receptor expressed in the membrane of NK cells. Tumour cells expressing NKG2DL become susceptible to an immune-dependent rejection mainly mediated by NK cells. The paradoxical roles of transforming growth factor beta (TGF-ß) in regulation of NKG2DL are presented in many studies, but the mechanism is unclear. In this study, we showed that TGF-ß up-regulated the expression of NKG2DLs in both PC3 and HepG2 cells. The up-regulation of NKG2DLs was characterized by increasing the expression of UL16-binding proteins (ULBPs) 1 and 2. TGF-ß treatment also increased the expression of transcription factor SP1. Knockdown of SP1 significantly attenuated TGF-ß-induced up-regulation of NKG2DLs in PC3 and HepG2 cells, suggesting that SP1 plays a key role in TGF-ß-induced up-regulation of NKG2DLs. TGF-ß treatment rapidly increased SP1 protein expression while not mRNA level. It might be due to that TGF-ß can elevate SP1 stability by activating PI3K/AKT signalling pathway, subsequently inhibiting GSK-3ß activity and decreasing the association between SP1 and GSK-3ß. Knockdown of GSK-3ß further verified our findings. Taken together, these results revealed that AKT/GSK-3ß-mediated stabilization of SP1 is required for TGF-ß induced up-regulation of NKG2DLs. Our study provided valuable evidence for exploring the tumour immune modulation function of TGF-ß.

Histone deacetylase inhibitors deplete myeloid-derived suppressor cells induced by 4T1 mammary tumors in vivo and in vitro.

Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored. In the present study, we provide the first demonstration that HDACi treatment decreases MDSC accumulation in the spleen, blood and tumor bed but increases the proportion of T cells (particularly the frequency of IFN-γ- or perforin-producing CD8+ T cells) in BALB/C mice with 4T1 mammary tumors. In addition, HDACi exposure of bone marrow (BM) cells significantly eliminated the MDSC population induced by GM-CSF or the tumor burden in vitro, which was further demonstrated as functionally important to relieve the inhibitory effect of MDSC-enriched BM cells on T cell proliferation. Mechanistically, HDACi increased the apoptosis of Gr-1+ cells (almost MDSC) compared with that of Gr-1- cells, which was abrogated by the ROS scavenger N-acetylcysteine, suggesting that the HDACi-induced increase in MDSC apoptosis due to increased intracellular ROS might partially account for the observed depletion of MDSC. These findings suggest that the elimination of MDSC using an HDACi may contribute to the overall anti-tumor properties of these agents, highlighting a novel property of HDACi as potent MDSC-targeting agents, which may be used to enhance the efficacy of immunotherapeutic regimens.

Nodal signaling modulates the expression of Oct-4 via nuclear translocation of ß-catenin in lung and prostate cancer cells.

Nodal is a member of transforming growth factor beta (TGF-ß) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the ß-catenin nuclear translocation. This increase was attributed to GSK-3ß dephosphorylating, and activin receptor-like kinase 4/7 (ALK4/7) played a major role in human cancer cells. Our study provides a positive understanding of Nodal function in cancer cells and suggests a potential novel target for clinical therapeutic research.

Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer.

Fusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The objective of this study was to identify Fn-infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn-IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti-Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC.