Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Examining the influence of organizational commitment on service quality through the lens of job involvement as a mediator and emotional labor and organizational climate as moderators.

This study investigates the impact of organizational commitment and job engagement on service quality, while integrating the influences of organizational climate and emotional labor. Utilizing data from 427 participants, acquired via structured questionnaires, the research employed the Statistical Package for the Social Sciences (SPSS) for analysis. The findings reveal that heightened job engagement and organizational commitment significantly enhance service quality, primarily through reinforcing employees' trust in their organization. A favorable organizational climate is instrumental in strengthening employees' affiliation with their organization, consequently leading to superior service provision. Furthermore, the capability to effectively regulate emotions emerges as a critical factor in both job engagement and the quality of service. The study advocates for augmenting job engagement and organizational commitment, cultivating a supportive workplace atmosphere, and equipping employees with resources for efficient emotional management. These strategies are proposed to substantially improve service quality. The insights derived from this research provide essential directives for managers striving to achieve service excellence.

Matrix metalloproteinase-9 overexpression in the hippocampus reduces alcohol-induced conditioned-place preference by regulating synaptic plasticity in mice.

Extracellular matrix proteins appear to be necessary for the synaptic plasticity that underlies addiction memory. In the brain, matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9), have been recently implicated in processes involving alcohol reward and memory. Here, we showed for the first time, the positive effects of MMP-9 on alcohol-induced conditioned place preference (CPP) behavior and hippocampal neuron plasticity in C57BL/6 mice. Using recombinant adeno-associated viruses to overexpress MMP-9 in the hippocampus, we investigated the NMDAR, PSD-95, and cellular cytoskeleton proteins F-actin/G-actin in the modulation of alcohol reward behavior in mice exposed to CPP. We found that hippocampal infusions of MMP-9 decreased alcohol-induced place preference suggesting a reduction in alcohol reward. Western blot analysis demonstrated that protein expression of NMDA receptors (GluN1, GluN2A and GluN2B) in the hippocampus of alcohol-exposed mice were higher than that of the saline group. Further, the expression of these proteins was decreased in MMP-9 overexpressing mice. MMP-9 also regulated the ratio of F-actin/G-actin (dendritic spines cytoskeleton proteins), which might be the key mediator for behavioral changes in mice. Consequently, our results highlight new evidence that MMP-9 may play an important role in the molecular mechanism underlying alcohol reward and preference.

A multi-strain probiotic blend reshaped obesity-related gut dysbiosis and improved lipid metabolism in obese children.

Background and aims: Obese children are more prone to becoming obese adults, and excess adiposity consequently increases the risk of many complications, such as metabolic syndromes, non-alcoholic fatty liver disease, cardiovascular disease, etc. This study aimed to evaluate the effects of multi-strain probiotics on the gut microbiota and weight control in obese children. Methods: A double-blind, randomized, placebo-controlled trial was carried out on overweight and obese children. Subjects received 12 weeks of treatment with supplementary probiotics that contained three strains: Lactobacillus salivarius AP-32, L. rhamnosus bv-77, and Bifidobacterium animalis CP-9, plus diet and exercise guidance. A total of 82 children were enrolled, and 53 children completed the study. Results: The supplementation of multi-strain probiotics resulted in a significant effect demonstrating high-density lipoprotein (HDL) and adiponectin elevation. At the same time, body mass index (BMI) and serum total cholesterol, low-density lipoprotein (LDL), leptin, and tumor necrosis factor-alpha (TNF-α) levels were reduced. Lactobacillus spp. and B. animalis were particularly increased in subjects who received probiotic supplements. The abundance of Lactobacillus spp. was inversely correlated with the ether lipid metabolism pathway, while that of B. animalis was positively correlated with serum adiponectin levels. Conclusion: Our results show that obesity-related gut dysbiosis can be reshaped by the supplementation of a multi-strain probiotic to improve lipid metabolism. The regular administration of a multi-strain probiotic supplement may be helpful for weight control and health management in overweight and obese children.

Integrated Analysis of ECT2 and COL17A1 as Potential Biomarkers for Pancreatic Cancer.

Background: Pancreatic cancer (PC) is a malignant tumor of the digestive tract. It presents with atypical clinical symptoms and lacks specific diagnostic indicators. This study is aimed at exploring the potential biomarkers of PC. Methods: TCGA database pancreatic cancer dataset was normalized and used to identify differentially expressed genes (DEGs). Survival, independent prognostic, and clinical correlation analyses were performed on DEGs to screen for key genes. DNA methylation, mutation, and copy number variation (CNV) analyses were used to analyze genetic variants in key genes. GSEA was performed to explore the functional enrichment of the key genes. Based on the expression of key genes, construction of a competing endogenous RNA (ceRNA) network, analysis of the tumor microenvironment (TME), and prediction of chemotherapeutic drug sensitivity were performed. Furthermore, the GEO database was used to validate the reliability of key genes. Results: Two key genes (ECT2 and COL17A1) were identified, which were highly expressed in PC. The mRNA expression of ECT2 and COL17A1 was associated with DNA methylation and CNV. The cell cycle, proteasome, and pathways in cancer were enriched in the high-COL17A1 and ECT2 groups. The TME results showed that immune scores were decreased in the high-ECT2 group. CeRNA network results showed that there were eleven miRNAs were involved in the regulation of ECT2 and COL17A1. Moreover, pRRophetic analysis showed that 20 chemotherapeutic drugs were associated with ECT2 and COL17A1 expression. Conclusions: Collectively, ECT2 and COL17A1 may be potential biomarkers for PC, providing a new direction for clinical diagnosis and treatment.

[A new method of microglia sorting and functional characteristics of spinal microglia in aged rats].

Objective: To establish an improved method of separating microglia from aged rats and to observe the biological characteristics of spinal microglia of aged rats. Methods: Young SD rats (2 months) were used as control group. Single cell suspension of rat microglia were prepared by trypsin, trypsin substitutes or mechanical net rubbing method. Then, by assessing the purity and survival rate of cells, and observing the morphological characteristics and analyzing the inflammatory functional characteristics, we optimized the isolation and purification method of microglia from aged rats (20 months old) , and observed the functional characteristics of spinal microglia in aged rats. Results: The survival rate of cells digested by pancreatic enzyme was low(young rats 83%, aged rats 60%). Although the survival rate of mechanical net rubbing method was higher than that of pancreatic enzyme digest methods (95%), the cell acquisition rate was lower(young rats(0.207±0.020)×106, aged rats(0.243±0.023)×106). Trypsin substitute dissociation combining density gradient centrifugation method was the best way to get abundant, active and higher survival microglia, and the purity reached more than 85%. We used this method to separate microglia from spinal cord of rats. Compared with the young rats, the spinal cord tissue of old rats was larger, the digestive fluid volume was higher, but the digestion time was shorter. Compared with the young rats, the aged rat spinal microglia had larger and rounder cell body, fewer and shorter protrusions, it tended to be activated morphologically, the level of proinflammatory cytokine IL-1ß of microglia in aged rats was lower, and the level of antiinflammatory factor IL-10 was higher. Conclusion: The method of trypsin substitute dissociation combined with density gradient centrifugation was successfully established to isolate and purify microglia from spinal cord of rats, the spinal microglia of old rats showed anti-inflammatory phenotype.

Endoloop-Assisted Polypectomy for a Symptomatic Giant Colonic Polyp in a Pediatric Patient.

Colonic polyps are a common cause of persistent bloody stools in pediatric patients. Such polyps are easily diagnosed by a barium study of the lower gastrointestinal tract or by colonoscopy. Polypectomies utilizing electric ligators are generally performed on pediatric patients, and such patients can be easily operated on. However, giant colonic polyps have been reported in pediatric patients. In the past, a laparotomy or laparoscopy would have been performed in some pediatric patients diagnosed with a giant colonic polyp; however, the large size, location, or position of the polyp would sometimes be too large or the location or position of the polyp would make successful operation difficult. In general, larger stumps with large feeding arteries are associated with larger colonic polyps. Therefore, if such a polyp is removed via electric polypectomy alone, there may be a higher risk of post-polypectomy bleeding from its stump. We report a case of a 14-year-old male patient who presented with a 2-month history of bloody stools. A giant juvenile colonic polyp was detected by colonoscopy in the transverse colon. Finally, we successfully removed the giant polyp by using endoloop-assisted polypectomy.

Drug-Induced Esophageal Ulcer in Adolescent Population: Experience at a Single Medical Center in Central Taiwan.

Background and Objectives: Drug-induced esophageal ulcer is caused by focal drug stimulation. It may occur in adults and children. Limited research is available in pediatric patients with drug-induced esophageal ulcer; therefore, we designed this study to determine the characteristics of this disease in this population. Materials and Methods: Thirty-two pediatric patients diagnosed with drug-induced esophageal ulcers from a hospital database of upper gastrointestinal tract endoscopies were included. After treatment, patients were followed for 2 months after upper gastrointestinal endoscopy. Results: Female patients were predominant (56.2%/43.8%). The mean age of patients was 15.6 years (median, 16 years; interquartile range, 2 years). Doxycycline was administered in most cases (56.3%); other drugs were dicloxacillin, amoxicillin, clindamycin, L-arginine, and nonsteroidal anti-inflammatory drugs. Doxycycline was associated with kissing ulcers. Esophageal ulcers induced by nonsteroidal anti-inflammatory drugs were more often associated with gastric or duodenal ulcers. The most common location was the middle-third of the esophagus (78.1%). Patients were treated with proton pump inhibitors, sucralfate, or H2-blockers. The mean duration for which symptoms lasted was 9.2 days. No esophageal stricture was found in 24 patients who were followed for 2 months after upper gastrointestinal endoscopy. Conclusions: The authors suggest informing patients to take medicine with enough water (approximately 100 mL) and enough time (15-30 min) before recumbency, especially high-risk drugs, such as doxycycline or nonsteroidal anti-inflammatory drugs.

A low serum iron level is a potential predictor of poor renal function in patients following laparoscopic sleeve gastrectomy: a retrospective study.

This study aimed to assess the association of serum iron level (Iron) with the estimated glomerular filtration rate (eGFR) after bariatric surgery (BS). We reviewed 210 patients with mean age of 39.1 ± 10.6 years (body mass index, 41.4 ± 5.5 kg/m2) undergoing BS. The primary outcome was the relationship between Iron and eGFR at 12-month after surgery. Multiple linear regression analyses were performed using postoperative eGFR as dependent variables and using Iron and other variables (i.e., age) as independent variables. At 12-month follow-up, 94 patients were analyzed. BMI significantly decreased, whereas serum iron level significantly increased. Although the percentage of patients with eGFR of < 90 mL/min/1.73 m2 increased during the study period, no significant difference was found in postoperative 12-month eGFR. No correlations were noted between Iron and eGFR at baseline and postoperative 1 and 6 months, whereas a significant relationship was observed between Iron and postoperative 12-month eGFR. Multiple linear regression analyses revealed that Iron and presence of diabetes were the independent predictors of postoperative 12-month eGFR. This pilot study showed a positive association of postoperative serum iron level with renal function in this patient population. Further large-scale trials are needed to confirm the findings.

Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency with SLC25A13 Mutation Presenting Hepatic Steatosis and Prolonged Jaundice. A Rare Case Report.

Background: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a rare autosomal recessive disease. The incidence of citrin deficiency is estimated between 1/10,000 and 1/20,000 in Taiwan. Case report: This report describes a case of a 42 day old female infant who suffered from prolonged jaundice, poor weight gain, and anemia. The initial total/direct bilirubin levels were 8.1/3.11 mg/dL. Liver biopsy was performed at 47 days old. The pathology revealed lobules marked with macrovesicular and microvesicular fatty metamorphosis. The serum amino acid profile showed elevated levels of threonine, methionine, citrulline, and arginine. Newborn screening disclosed normal results, but the genetic study revealed SLC25A13 mutation 851-854 del and 615 + 5G > A. The genetic study of her parents showed that the father carried the SLC25A13 mutation 851-854 del and the mother carried the SLC25A13 mutation 615 + 5G > A. Treatment with ursodeoxycholic acid decreased the bilirubin levels to a normal range at the age of 5 months. Conclusion: This report illustrates that hepatic steatosis is a feature of NICCD. For every young infant patient who develops cholestasis, the pediatrician must consider NICCD as a differential diagnosis even if newborn screening shows normal findings.

[Nutrition Demand and Care of Patients Undergoing Bariatric Surgery].

The increasing prevalence of obesity and comorbid conditions worldwide requires the development of effective strategies for both treatment and prevention. In recent years, bariatric surgery has emerged as the most effective weight-loss therapy for individuals affected by moderate and morbid obesity. Behavioral alterations in eating patterns and anatomical and physiological modifications to the gastrointestinal organs may result in significant deficiencies in protein and micronutrients such as iron, folate, Vitamin B12, and thiamin. Many individuals with obesity have already-existing nutritional deficiencies before receiving bariatric procedures. The preoperative screening for and correction of micronutrient deficiencies preoperatively are crucial, as these deficiencies may be further exacerbated by the bariatric procedures. Because a balanced diet is key to successful weight loss at all stages of treatment, after the operation, patients should consume a diet that is low calorie and rich in protein, choose foods of the proper volume and consistency, and drink an appropriate amount of fluids. Maintaining a proper diet will enable patients to avoid unpleasant sensations after surgery and improve the phenomenon of inadequate nutritional needs.

Cyproheptadine, an epigenetic modifier, exhibits anti-tumor activity by reversing the epigenetic silencing of IRF6 in urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the second most common malignancy of the urinary system with high rate of recurrence, UC patients therefore needed to be treated with surgery followed by chemotherapy. Development of novel therapeutics with minimal side-effect is an urgent issue. Our previous study showed that cyproheptadine (CPH), an anti-histamine, exhibited antitumor activity in UC in vitro and in an xenograft model. However, the molecular mechanism of how CPH inhibits tumor progression is not fully understood. METHODS: Genes that were upregulated after treatment with CPH in UC cells, were examined by RNA-Seq. Real-time quantitative PCR (RT-qPCR) was employed to detect IRF6 expression while COBRA assay and bisulphite pyrosequencing were used to examine promoter methylation of IRF6. Enrichment of total H3K27 acetylation and H3K4 mono-methylation were detected by western blotting. Colony formation and flow cytometry were used to examine proliferation and apoptosis in UC cells overexpressed or depleted with IRF6. Nude mice xenograft model was used to examine the effect of IRF6 in UC. RESULTS: Our result showed that several genes, including IRF6 were upregulated after treatment with CPH in BFTC905 UC cells. Further experiments found that treatment of CPH could restore the expression of IRF6 in several other UC cell lines, probably due to promoter hypomethylation and enrichment of H3K27 acetylation and H3K4 mono-methylation. These results may be due to the fact that CPH could alter the activity, but not the expression of epigenetic modifiers. Finally, re-expression of IRF6 in UC inhibited tumor growth in vitro and in an xenograft mouse model, by inducing apoptosis. CONCLUSION: In conclusion, our results suggested that CPH may be an epigenetic modifier, modulating the expression of the potential tumor suppressor IRF6, in inhibiting tumor growth in UC.

Epigenetic Silencing of STAT3-Targeted miR-193a, by Constitutive Activation of JAK/STAT Signaling, Leads to Tumor Progression Through Overexpression of YWHAZ in Gastric Cancer.

PURPOSE: The purpose of this study was to identify genes that were epigenetically silenced by STAT3 in gastric cancer. METHODS: MBDcap-Seq and expression microarray were performed to identify genes that were epigenetically silenced in AGS gastric cancer cell lines depleted of STAT3. Cell lines and animal experiments were performed to investigate proliferation and metastasis of miR-193a and YWHAZ in gastric cancer cell lines. Bisulfite pyrosequencing and tissue microarray were performed to investigate the promoter methylation of miR-193a and expression of STAT3, YWHAZ in patients with gastritis (n = 8) and gastric cancer (n = 71). Quantitative methylation-specific PCR was performed to examine miR-193a promoter methylation in cell-free DNA of serum samples in gastric cancer patients (n = 19). RESULTS: As compared with parental cells, depletion of STAT3 resulted in demethylation of a putative STAT3 target, miR-193a, in AGS gastric cancer cells. Although bisulfite pyrosequencing and epigenetic treatment confirmed that miR-193a was epigenetically silenced in gastric cancer cell lines, ChIP-PCR found that it may be indirectly affected by STAT3. Ectopic expression of miR-193a in AGS cells inhibited proliferation and migration of gastric cancer cells. Further expression microarray and bioinformatics analysis identified YWHAZ as one of the target of miR-193a in AGS gastric cancer cells, such that depletion of YWHAZ reduced migration in AGS cells, while its overexpression increased invasion in MKN45 cells in vitro and in vivo. Clinically, bisulfite pyrosequencing revealed that promoter methylation of miR-193a was significantly higher in human gastric cancer tissues (n = 11) as compared to gastritis (n = 8, p < 0.05). Patients infected with H. pylori showed a significantly higher miR-193a methylation than those without H. pylori infection (p < 0.05). Tissue microarray also showed a positive trend between STAT3 and YWHAZ expression in gastric cancer patients (n = 60). Patients with serum miR-193a methylation was associated with shorter overall survival than those without methylation (p < 0.05). CONCLUSIONS: Constitutive activation of JAK/STAT signaling may confer epigenetic silencing of the STAT3 indirect target and tumor suppressor microRNA, miR-193a in gastric cancer. Transcriptional suppression of miR-193a may led to overexpression of YWHAZ resulting in tumor progression. Targeted inhibition of STAT3 may be a novel therapeutic strategy against gastric cancer.

Salivary dysbiosis in Sjögren's syndrome and a commensal-mediated immunomodulatory effect of salivary gland epithelial cells.

Salivary gland epithelial cells (SGECs) have been implicated in the pathogenesis of Sjögren's syndrome due to aberrant antigen-presentation function. This study examined the hypothesis that oral dysbiosis modulates the antigen-presentation function of SGECs, which regulates CD4 T cell proliferation in primary Sjögren's syndrome (pSS). Saliva samples from 8 pSS patients and 16 healthy subjects were analyzed for bacterial 16S ribosomal DNA. As a result, 39 differentially abundant taxa were identified. Among them, the phylum Proteobacteria comprised 21 taxa, and this phylum was mostly enriched in the healthy controls. The proteobacterium Haemophilus parainfluenzae was enriched in the healthy controls, with the greatest effect size at the species level. Treatment of A253 cells in vitro with H. parainfluenzae upregulated PD-L1 expression, and H. parainfluenzae-pretreated A253 cells suppressed CD4 T cell proliferation. The suppression was partially reversed by PD-L1 blockade. Among low-grade xerostomia patients, salivary abundance of H. parainfluenzae decreased in pSS patients compared to that in non-pSS sicca patients. Our findings suggest that H. parainfluenzae may be an immunomodulatory commensal bacterium in pSS.

Alkaline substances gastroesophageal injury in young children: emphasis on Asian food preparation habits.

BACKGROUND: Ingestion of alkaline substances should not be disregarded because a small amount can cause chemical burns in the esophagus, with esophageal stricture being the most common late complication. METHODS: We enrolled children with alkaline corrosive damage receiving treatment at China Medical University Children's Hospital's emergency department between 2008 and 2018. Patients were divided into groups A (ingested causative agents other than alkaline oil), and B (ingested alkaline oil). RESULTS: Altogether, 40 (27 [67.5%] male and 13 [32.5%] female) patients aged 7 months-7 years were enrolled. The most commonly ingested agent was alkaline oil (13 cases, 32.5%), followed by oven and drainage cleaners (8 cases, 20%), bleach (6 cases, 15%), laundry and dish cleaners (4 cases, 10%), sodium hydroxide (4 cases, 10%), sodium carbonate (2 cases, 5%), sodium phosphate (2 cases, 5%), and sodium citrate (1 case, 2.5%). High proportions of children had esophagitis (40/40, 100%), erosive gastritis (7/40, 17.5%), and gastric ulcer (6/40, 15%). The incidence of esophageal stricture was 38.4% (5/13) and 7.4% (2/27) in groups B and A, respectively. In group B, 4 children developed growth stunting or malnutrition during the first decade after onset, with reduced immunity and feelings of inferiority. CONCLUSION: Alkaline ingestion usually results in esophageal injury that is difficult to cure. Corrosive esophageal strictures cause swallowing difficulties and growth stunting in children. Young children who ingested alkaline oil have more complications. Given that alkaline corrosive injuries are often accidental, prevention of corrosive agent ingestion is crucial.

Helios Expression in Tumor-Infiltrating Lymphocytes Correlates with Overall Survival of Advanced Gastric Cancer Patients.

Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on the activation status and/ or their microenvironments. Here, we examined the expression of a specific zinc finger transcription factor, Helios (IKZF2), in gastric tumor-infiltrating lymphocytes by immunohistochemistry and the correlation with survival. Segregation of gastric cancer patients into high- vs. low-Helios-expressing tumor-infiltrating lymphocytes showed those with high expression to exhibit longer survival in gastric cancer patients, Helicobacter pylori-infected gastric cancer patients and advanced stage (III-IV) gastric cancer patients. In particular, Helios expression was an independent factor for survival in advanced gastric cancer patients. We performed immunofluorescence staining to detect Helios expression in tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. We found that Helios is expressed more in CD4+ T cells and little in CD8+ T cells in infiltrated lymphocytes in gastric cancer. In summary, we believe that the study of specific characteristics of tumor-infiltrating lymphocytes can delineate the interactions of immune and tumor cells to improve upon immunotherapy strategies.

Differential DNA methylation profiles of peripheral blood mononuclear cells in allergic asthmatic children following dust mite immunotherapy.

BACKGROUND/PURPOSE: Allergen-specific immunotherapy (SIT) is now considered curative to allergic diseases such as asthma. Mechanistically, our previous work showed DNA hypermethylation of cytokine genes, in T-helper cells, in allergic asthmatic children treated with allergen-SIT. In this study, we extended to work to assess possible changes in the DNA methylomes of peripheral blood mononuclear cells (PBMCs), isolated from mite allergen-SIT asthmatic children, to explore further the underlying methylation changes. METHODS: Thirteen allergic asthmatic children who received Der p-SIT, 12 non-SIT allergic asthmatic controls, and 12 healthy controls were enrolled. Bisulfite-converted DNA from Der p-stimulated PBMCs was analyzed using Human Methylation 450 k BeadChip. Pyrosequencing and quantitative real-time PCR were used to validate the DNA methylation levels and the gene expression of individual samples. RESULTS: We identified 108 significantly differentially methylated regions (DMRs) unique to Der p-treated PBMCs, with 53 probes linked to demethylated DMRs, and 55 probes linked to methylated DMRs. Three associated genes (BCL6, HSPG2, and HSP90AA1), of selected DMRs, were subjected to bisulfite pyrosequencing. Of these, BCL6 showed significant hypomethylation, while HSPG2 and HSP90AA1 were hypermethylated in SIT group, compared to the AA group. Furthermore, SIT group had significantly higher gene expression of BCL6 and lower gene expression of HSPG2. KEGG pathway analysis further revealed DMR genes involved in ECM-receptor interactions, asthma, and antigen processing and presentation pathways. CONCLUSIONS: Several DNA regions showed DNA methylation altered by Der p specific immunotherapy, indicating desensitization-associated methylomes. Genes belonging to these SIT-altered pathways may represent therapeutic targets for better clinical management of asthma.

Allicin enhances the radiosensitivity of colorectal cancer cells via inhibition of NF-κB signaling pathway.

Radioresistance is an important factor affecting the radiotherapy effect of colorectal cancer (CRC). Allicin is a versatile sulfur-containing organic compound extracted from garlic (Allium sativum L.), which has many pharmacological effects. However, the effect of allicin on the sensitivity of CRC radiotherapy has not been confirmed. The present study is to observe the radiosensitivity effects of allicin and to explore its mechanism in CRC radiotherapy. The proliferation inhibition effects of allicin combined with X-ray radiotherapy in HCT116 cells were measured by growth curve of cell and colony formation assays. The cell apoptosis was detected by Hoechst 33258 nucleus staining assay. The migration ability of cells was detected by Transwell chamber migration assay. The animal model of CRC was established in BALB/c mice via transplantation of CT26 cell, and the radiosensitization effect of allicin on CRC was detected in vivo. The mRNA expressions of NF-κB, IKKß, and IκBα were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of NF-κB, p-NF-κB, IKKß, p-IKKß, IκBα, and p-IκBα were detected by western blotting. Our results showed that allicin improves the sensitivity of X-ray radiotherapy in CRC, and its mechanism may be associated with inhibition of NF-κB signaling pathway. These findings suggest that allicin may be used as a potential sensitizer for tumor radiotherapy in the clinic.

Characteristics of regulatory T-cell function in patients with chronic hepatitis B and C coinfection.

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy-four untreated HBV/HCV co-infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV-active/HCV-active (BACA), HBV-inactive/HCV-active (BICA), HBV-active/HCV-inactive (BACI) and HBV-inactive/HCV-inactive (BICI). Treg frequency was calculated as the fraction of CD4+ Foxp3+ T cells among CD4+ T cells. Treg-mediated inhibition was measured as percent of inhibition of T-cell proliferation. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4+ Foxp3+ T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis-4 (FIB-4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN-γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co-infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.