Retrospective comparison of endoscopic transoral and bilateral areolar approaches for thyroglossal cyst resection: a single-centre experience.

PURPOSE: Our study aimed to compare the efficacy, safety, and clinical effect of the transoral approach and the bilateral areolar approach (BAA) for endoscopic thyroglossal duct cyst (TGDC) resection. METHODS: In total, 42 patients who received an endoscopic TGDC resection between January 2019 and May 2022 via a transoral (n = 22) or bilateral areolar (n = 20) approach by a single surgeon were retrospectively enrolled. We collected and compared the following data: patients' demographic data, complication events, operative time, bleeding volume, drainage volume, 6-h postoperative pain scores, length of hospitalisation, resected TGDC size, and cosmetic satisfaction. RESULTS: There were no cases of conversion to a transcervical approach in the two groups. No significant differences were found between the two groups in terms of age, sex, body mass index, complication, bleeding volume, 6-h postoperative pain scores, and TGDC size (all p > 0.05). However, the operative time and patients' cosmetic satisfaction were higher in the transoral group than in the BAA group (all p < 0.05). In addition, the drainage volume and length of hospitalisation in the transoral group were less than those in the BAA group (all p < 0.05). CONCLUSIONS: Both the transoral approach and BAA are safe and reliable; however, the transoral approach is more complex than the BAA and offers better cosmetic satisfaction. Doctors should choose the appropriate surgical procedure based on the patient's condition and preferences.

Association between adult food insecurity and self-reported asthma in the United States: NHANES 2003-2018.

OBJECTIVE: Asthma is a chronic disease of the lungs. The development of asthma is related to various risk factors. Food insecurity is a critical social determinant of health, although there is little information on the association between adult food insecurity and asthma. The purpose of this study is to explore the potential correlation in US adults. METHODS: The study population data were extracted from NHANES 2003-2018. Food insecurity was measured using the USDA FSSM and categorized as full, marginal, low, or very low food security. The assessment of self-reported asthma was determined by self-report questionnaires. The self-reported positive outcomes were that participants had asthma and a history of asthma attacks and asthma-related ER visits in the past year. We developed two multivariate logistic regression models. Stratified analyses were performed by gender and age. RESULTS: A total of 38,077 participants were considered in our final analysis. Compared to participants with FFS, the ORs (95% CIs) for asthma were 1.16 (1.00-1.33), 1.42 (1.23-1.64), and 1.56 (1.34-1.80) for participants with MFS, LFS, and VLFS, respectively (Model II). Additionally, after full adjustment, individuals with VLFS had 49% greater risks of asthma attacks (OR = 1.49; 95% CI 1.13-1.97). The ORs (95% CIs) for asthma-related ER visits were 1.59 (1.14-2.23) and 1.98 (1.36-2.87) for participants with LFS and VLFS, respectively (Model II). The positive correlations remained robust when stratified by gender and age. CONCLUSION: Our research showed that food insecurity among US adults was associated with asthma, asthma attacks, and asthma-related ER visits.

Hsa_circ_0001073 targets miR-626/LIFR axis to inhibit lung cancer progression.

Circular RNAs (circRNAs) are associated with lung cancer progression. However, it is unclear whether and how circRNA hsa_circ_0001073 (circ_0001073) are involved in lung cancer progression. circ_0001073, microRNA (miR)-626, and leukemia inhibitory factor receptor (LIFR) abundances were determined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, invasion, and apoptosis were analyzed by cell counting kit-8, transwell analysis and flow cytometry, respectively. The target correlation was tested by dual-luciferase reporter analysis or RNA immunoprecipitation. Results showed that circ_0001073 abundance was down-regulated in lung cancer cells. circ_0001073 constrained cell viability and invasion and facilitated apoptosis in lung cancer cells. miR-626 was targeted via circ_0001073, and circ_0001073 inhibited lung cancer progression via reducing miR-626 expression. LIFR was targeted via miR-626, and miR-626 knockdown constrained cell viability and invasion and facilitated apoptosis in lung cancer cells via up-regulating LIFR. circ_0001073 increased LIFR expression via miR-626 in lung cancer cells. In conclusion, circ_0001073 represses lung cancer progression via miR-626/LIFR axis, indicating the potential value of circ_0001073 in lung cancer treatment.

Retracted: miR-145 modulates epithelial-mesenchymal transition and invasion by targeting ZEB2 in non-small cell lung cancer cell lines.

Lung cancer is the leading cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a major event that drives cancer progression. Here we aim to investigate the role of microRNA, miR-145, in regulating EMT of the highly invasive non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction analysis indicated that miR-145 was downregulated in cancer tissue compared with that in adjacent normal tissue. NSCLC cell lines, namely H1299, PC7, and SPCA-1, also demonstrated miR-145 downregulation, which is correlated well with their invasive ability, assessed by the Matrigel invasion assay. miR-145 overexpression resulted in downregulation of N-cadherin, and downregulation of vimentin and E-cadherin, suggesting a decreased EMT activity. TargetScan analysis predicted that a binding site exists between miR-145 and an oncogene, ZEB2, which was verified using the dual-luciferase assay. Alteration of miR-145 expression also induced inverse effects on ZEB2 expression, and a negative correlation exists between ZEB2 and miR-145 in human tissues. ZEB2 and miR-145 also exerted antagonizing effects on the invasion of NSCLC cells. Therefore, miR-145 is an important molecule in NSCLC that regulates cancer EMT through targeting ZEB2.

Risk factors of coronary artery stenosis in patients with obstructive sleep apnoea: a prospective study.

OBJECTIVE: To investigate the prevalence of coronary artery disease and characteristics of coronary artery in patients with obstructive sleep apnoea. METHODS: The prospective study was conducted at the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China, from January, 2012, to June, 2015, and comprised consecutive patients with diagnosed obstructive sleep apnoea. High-resolution 320-slice coronary computed tomography was performed in all the patients. Data was evaluated for the presence of coronary lumen narrowing. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for multivariate analysis of independent risk factors. SPSS 16 was used for data analysis. RESULTS: Of the 277 patients, 186(67.14%) were males. The overallmean age was 55.1±14.3 years. Coronary artery disease was found in 41(14.8%) patients. Prospective Cardiovascular Münster score, uric acid, triglyceride, C-reactive protein, apnoea hypopnoea index, Epworth sleepiness scale values were significantly higher in patients with the disease (p<0.05 each). Higher Prospective Cardiovascular Münster score, C-reactive protein, apnoea hyponoea index levels had a significant ability to reflect the occurrence of coronary artery disease (p<0.05 each). CONCLUSIONS: Coronary heart disease occurrence in obstructive sleep apnoea patients was found to be strongly related to Prospective Cardiovascular Münster score, apnoea hyponoea index and Creactive protein level.

Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

Overexpression of lncRNA HOXA11-AS promotes cell epithelial-mesenchymal transition by repressing miR-200b in non-small cell lung cancer.

BACKGROUND: Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). METHODS: The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan-Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells. RESULTS: The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC. CONCLUSIONS: Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial-mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.

Utility of uric acid as a risk marker of extubation success in chronic obstructive pulmonary disease.

BACKGROUND: The objective of this observational study was to determine whether there is an association between extubation success and uric acid in chronic obstructive pulmonary disease patients with mechanical ventilation admitted to the intensive care units, and identify the risk markers for extubation success in COPD patients with mechanical ventilation. METHODS: Consecutive COPD patients with intubation were screened at baseline. The study included patients on mechanical ventilation (MV) for over 12 hours and who, in the process of weaning, were subjected to low-level pressure support. Exclusion criteria were age under 18 years, ventilation via tracheotomy, and patients failing to cooperate for different reasons. The final study population consisted of 106 patients. Demographic, clinical, laboratory, and mechanical ventilation parameters were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid on admission, duration of mechanical ventilation, pressure support ventilation, and APACHE II score on admission were significantly higher in COPD patients with extubation failure than in those with extubation success (p < 0.05), but lower tidal volume before weaning was observed in COPD patients with extubation failure. Among these patients, multiple logistic analyses indicated the independent risk factors for extubation success in the COPD subjects included serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. The diagnosis analysis showed that higher uric acid level and APACHE II score on admission and longer duration of mechanical ventilation had a significant ability to reflect extubation success in the COPD patients with respiratory failure. CONCLUSIONS: The novel finding of this study is that the extubation failure in COPD patients with respiratory failure is strongly related to serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. These results might be helpful for selecting the best time to remove the tracheal intubation and improving extubation success rate in COPD patients with respiratory failure.

Unraveling the hierarchical structure of posture and muscle activity changes during mating of Caenorhabditis elegans.

One goal of neurobiology is to explain how decision-making in neuromuscular circuits produces behaviors. However, two obstacles complicate such efforts: individual behavioral variability and the challenge of simultaneously assessing multiple neuronal activities during behavior. Here, we circumvent these obstacles by analyzing whole animal behavior from a library of Caenorhabditis elegans male mating recordings. The copulating males express the GCaMP calcium sensor in the muscles, allowing simultaneous recording of posture and muscle activities. Our library contains wild type and males with selective neuronal desensitization in serotonergic neurons, which include male-specific posterior cord motor/interneurons and sensory ray neurons that modulate mating behavior. Incorporating deep learning-enabled computer vision, we developed a software to automatically quantify posture and muscle activities. By modeling, the posture and muscle activity data are classified into stereotyped modules, with the behaviors represented by serial executions and transitions among the modules. Detailed analysis of the modules reveals previously unidentified subtypes of the male's copulatory spicule prodding behavior. We find that wild-type and serotonergic neurons-suppressed males had different usage preferences for those module subtypes, highlighting the requirement of serotonergic neurons in the coordinated function of some muscles. In the structure of the behavior, bi-module repeats coincide with most of the previously described copulation steps, suggesting a recursive "repeat until success/give up" program is used for each step during mating. On the other hand, the transition orders of the bi-module repeats reveal the sub-behavioral hierarchy males employ to locate and inseminate hermaphrodites.

High Monocyte-to-Lymphocyte Ratio is Associated with Obstructive Sleep Apnea Hypopnea Syndrome.

Objective: This study aims to explore the correlation between serum monocyte-to-lymphocyte ratio (MLR) and other inflammatory parameters with the occurrence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in patients. Methods: This study included 310 patients who underwent polysomnography monitoring at our hospital between January 2021 and January 2023. Routine blood inflammatory parameters and polysomnography (PSG) results were also evaluated. The differences in inflammatory markers between the OSAHS and normal groups were compared, and OSAHS independent related factors were screened. Results: The MLR of OSAHS group was significantly higher than that of control group, and the difference was statistically significant. Multivariate logistic regression analysis suggested that MLR is an independent risk factor for OSAHS. Conclusion: High MLR was correlated with OSAHS. The diagnostic value of MLR was better than that of the other inflammatory parameters.

Identification of immunocell infiltrates and effective diagnostic biomarkers in laryngeal carcinoma.

Laryngeal cancer (LC) is a malignant tumor that occurs in the head and neck. Laryngeal cancer is one of the most common cancers of the neck and head, and its prognosis has always been poor. The incidence of LC increased gradually and showed an early rising trend. Laryngeal cancer is rarely studied in relation to immunity, Malignant tumors will change the state of the human body in various ways to adapt to their own survival and avoid the immune system. This study aims to explore the immune molecular mechanism of laryngeal cancer through bioinformatics analysis. The gene expression data was downloaded for 3 microarray datasets: GSE27020, GSE59102, and GSE51985. CIBERSORT algorithm was performed to evaluate immune cell infiltration in tissues between LC and healthy control (HC). Differentially expressed genes (DEGs) were screened. Functional correlation of DEGs were analyzed by Gene Ontology, Gene Set Enrichment Analysis and Kyoto encyclopedia of genes and genomes. Candidate biomarkers were identified by cytoHubba of Cytoscape. Spearman correlations between the above biomarkers and infiltrating immune cells were explored using R software analysis. The immune cell types of LC and HC were significantly different. Twenty-one DEGs were obtained by cross-screening. The function of DEGs is closely related to the number of immune cells. Five central genes (TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4) were screened. The HUB gene was demonstrated to have the ability to diagnose LC and HC with good specificity and sensitivity. The correlation between immune cells and biomarkers showed that hub gene was positively correlated with macrophages and dendritic cells, and negatively correlated with CD4 + T cell. TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4 can be used as diagnostic biomarker for LC. Macrophages, dendritic cells and CD4 + T cell may participate in the occurrence and development of LC.

Sparcl1 and Atherosclerosis.

Atherosclerosis and its complications constitute some of the major diseases affecting humans worldwide. A core component of atherogenesis is endothelial cell damage and dysfunction, which also includes factors such as adhesion and proliferation of various cells. Multiple studies have shown that atherosclerosis and cancer share a common pathophysiological process and exhibit a degree of similarity. Sparcl-1 is a cysteine-rich secretory stromal cell protein present in the extracellular matrix and belongs to the Sparc family of proteins. Its role in tumor development has been widely investigated; however, its role in cardiovascular diseases has rarely been studied. Sparcl-1 is considered an oncogene correlated with the regulation of cell adhesion, migration, and proliferation and is also related to blood vessel integrity. In this review, the potential link between Sparcl-1 and atherosclerosis development is investigated, and recommendations on future research on the role of Sparcl-1 in atherogenesis are provided.

Cryptotanshinone Reverses Corticosteroid Insensitivity by Inhibition of Phosphoinositide-3-Kinase-δ in Chronic Obstructive Pulmonary Disease.

Purpose: Corticosteroid insensitivity has become a major barrier in the treatment of chronic obstructive pulmonary disease (COPD). It is known that oxidative stress reduces the expression and activity of histone deacetylase (HDAC)-2 by activating phosphoinositide-3-kinase-δ(PI3Kδ)/Akt pathway, which is a common mechanism. The aim of this study was to investigate whether cryptotanshinone (CPT) can improve corticosteroid sensitivity and to investigate the molecular mechanisms by which this occurs. Patients and Methods: Corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) collected from COPD patients, or in human monocytic U937 monocytic cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α (TNFα)-induced interleukin 8 (IL-8) production in the presence or absence of cryptotanshinone. PI3K/Akt activity (measured as the relative ratio of phosphorylated Akt at Ser-473 to total Akt) and HDAC2 expression levels were determined by western blotting. HDAC activity was evaluated by a Fluo-Lys HDAC activity assay kit in U937 monocytic cells. Results: Both PBMCs in patients with COPD and U937 cells exposed to CSE were found to be insensitive to dexamethasone, accompanied by increased phosphorylated Akt (pAkt) and decreased HDAC2 protein expression. The pretreatment of cryptotanshinone restored their sensitivity to dexamethasone, and simultaneously downregulated the level of phosphorylated Akt and upregulated the level of HDAC2 protein. Pretreatment with cryptotanshinone or IC87114 reversed the decrease in HDAC activity in CSE-stimulated U937 cells. Conclusion: Cryptotanshinone restores corticosteroid sensitivity induced by oxidative stress via inhibition of PI3Kδ and is a potential treatment for corticosteroid-insensitive diseases such as COPD.

USP9X expression is functionally related to laryngeal cancer.

An increasing number of studies have shown that USP9X is closely related to cancer. However, its role in carcinogenesis and progression of laryngeal cancer has not yet been investigated. In this study, we found that USP9X was upregulated in laryngeal cancer tissues. The expression of USP9X was significantly correlated with degree of laryngeal cancer differentiation and lymphatic metastasis. USP9X knockdown led to a decrease in the ability of proliferation, migration, and invasion of FaDu cells. The proportion of FaDu apoptotic cells increased by interfering with the endogenous expression of USP9X. We speculated that inhibiting USP9X might induce apoptosis in FaDu cells by downregulating Mcl-1 and upregulating Bax protein expression. Our findings for the first time suggest the expression level and trend of USP9X in laryngeal cancer tissue and USP9X may plays an important role in promoting the occurrence and progression of laryngeal cancer. USP9X may be a potential target for intervention in treatment of laryngeal cancer.

Stearoyl-CoA desaturases sustain cholinergic excitation and copulatory robustness in metabolically aging C. elegansmales.

Regulated metabolism is required for behaviors as adults age. To understand how lipid usage affects motor coordination, we studied male Caenorhabditis elegans copulation as a model of energy-intensive behavior. Copulation performance drops after 48 h of adulthood. We found that 12-24 h before behavioral decline, males prioritize exploring and copulation behavior over feeding, suggesting that catabolizing stored metabolites, such as lipids, occurs during this period. Because fat-6/7-encoded stearoyl-CoA desaturases are essential for converting the ingested fatty acids to lipid storage, we examined the copulation behavior and neural calcium transients of fat-6(lf); fat-7(lf) mutants. In wild-type males, intestinal and epithelial fat-6/7 expression increases during the first 48 h of adulthood. The fat-6(lf); fat-7(lf) behavioral and metabolic defects indicate that in aging wild-type males, the increased expression of stearoyl-CoA desaturases in the epidermis may indirectly modulate the levels of EAG-family K+ channels in the reproductive cholinergic neurons and muscles.

Promising novel biomarkers and candidate small-molecule drugs for lung adenocarcinoma: Evidence from bioinformatics analysis of high-throughput data.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer associated with an unstable prognosis. Thus, there is an urgent demand for the identification of novel diagnostic and prognostic biomarkers as well as targeted drugs for LUAD. The present study aimed to identify potential new biomarkers associated with the pathogenesis and prognosis of LUAD. Three microarray datasets (GSE10072, GSE31210, and GSE40791) from the Gene Expression Omnibus database were integrated to identify the differentially expressed genes (DEGs) in normal and LUAD samples using the limma package. Bioinformatics tools were used to perform functional and signaling pathway enrichment analyses for the DEGs. The expression and prognostic values of the hub genes were further evaluated by Gene Expression Profiling Interactive Analysis and real-time quantitative polymerase chain reaction. Furthermore, we mined the "Connectivity Map" (CMap) to explore candidate small molecules that can reverse the tumoral of LUAD based on the DEGs. A total of 505 DEGs were identified, which included 337 downregulated and 168 upregulated genes. The PPI network was established with 1,860 interactions and 373 nodes. The most significant pathway and functional enrichment associated with the genes were cell adhesion and extracellular matrix-receptor interaction, respectively. Seven DEGs with high connectivity degrees (ZWINT, RRM2, NDC80, KIF4A, CEP55, CENPU, and CENPF) that were significantly associated with worse survival were chosen as hub genes. Lastly, top 20 most important small molecules which reverses the LUAD gene expressions were identified. The findings contribute to revealing the molecular mechanisms of the initiation and progression of LUAD and provide new insights for integrating multiple biomarkers in clinical practice.

RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy.

Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138-/- mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.

Dynamic changes of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and natural killer T (NKT) cells in patients with acute hepatitis B infection.

BACKGROUND: The goal of this study is to observe changes in HBcAg-specific cytotoxic T lymphocytes (CTLs), natural killer (NK) and natural killer T (NKT) cells from peripheral blood and to relate such changes on viral clearance and liver injury in patients with acute hepatitis B (AHB). METHODS: Dynamic profiles on the frequency of HLA-A0201-restricted HBcAg18-27 pentamer complex (MHC-Pentamer)-specific CTLs and lymphocyte subsets in AHB patients were analyzed in addition to liver function tests, HBV serological markers, and HBV DNA levels. ELISPOT was used to detect interferon-gamma (INF-γ) secretion in specific CTLs stimulated with known T cell epitope peptides associated with HBV surface protein, polymerase, and core protein. RESULTS: HBV-specific CTL frequencies in AHB patients were much higher than in patients with chronic hepatitis B (CHB) (p<0.05). HBeAg and HBV DNA disappeared earlier in AHB patients with a high frequency of HBV-specific CTLs compared with those with a low frequency of HBV-specific CTLs (p=0.001 and 0.024, respectively). INF-γ spots of effector cells stimulated by Pol575-583, Env348-357, or Core18-27 epitope peptides were significantly greater in AHB patients than in CHB patients (p<0.01). CD3+CD8+ T cell numbers in AHB patients was more than observed in the healthy control group from the first to the fourth week after admission (p=0.008 and 0.01, respectively); the number of CD3+CD8+ T cells and frequency of HBcAg18-27-specific CTLs in AHB patients reached peak levels at the second week after admission. NK and NKT cell numbers were negatively correlated with the frequency of HBcAg-specific CTLs (r=-0.266, p=0.05). CONCLUSIONS: Patients with AHB possess a higher frequency of HBcAg-specific CTLs than CHB patients. The frequency of specific CTLs in AHB patients is correlated with HBeAg clearance indicating that HBV-specific CTLs play an important role in viral clearance and the self-limited process of the disease. Furthermore, NK and NKT cells are likely involved in the early, non-specific immune response to clear the virus.

The expression of NLK is functionally associated with colorectal cancers (CRC).

The regulatory mechanism of NLK in the carcinomagenesis and progression of colorectal cancer (CRC) remains unclear. Here, we identified a single nucleotide polymorphism (SNP) site of NLK (rs2125846) as a new susceptibility locus for CRC risk located within an intron of the human NLK gene in a Chinese population. NLK downregulation led to a decrease in the ability of proliferation and migration of RKO cells in vitro. The proportion of RKO apoptotic cells increased by interfering with the endogenous expression of NLK. We speculate that LncRNA XIST may upregulate NLK expression by downregulating miR-92b-3p, thereby promote the development of CRC. These results provide important information for the identification of novel potential targets for the prevention or treatment of CRC.

Inhibition of Kelch-like epichlorohydrin-related protein 1 promotes the progression and drug resistance of lung adenocarcinoma.

BACKGROUND: Lung cancer is a common malignant carcinoma of respiratory system with high morbidity and mortality. Kelch-like epichlorohydrin-related protein 1 (Keap1), a member of the BTB-Kelch protein family, has been reported as an important molecule in several cancers. However, its potential role in tumor is still controversial. Here we aim to clarify the effect of Keap1 on the biological characteristics and chemotherapy resistance in lung adenocarcinoma (LUAD). METHODS: Immunohistochemistry was conducted to compare Keap1 expression in lung adenocarcinoma tissues and matched non-cancerous tissues, and the correlation between Keap1 expression and clinicopathological features was analyzed. Subsequently, the stable A549 and H1299 cell lines with Keap1 knockdown or overexpression were constructed using lentivirus. The roles of Keap1 on the cell proliferation, migration, invasion and drug resistance were investigated by colony formation assay, cell proliferation assay, wound scratch test, transwell invasion assay and drug sensitivity assay, respectively. RESULTS: Keap1 was lowly expressed in tumor tissues compared to matched non-cancerous tissues, and its expression was correlated with TNM stage and lymph node metastasis. Early stage (I) tumors without lymph node metastasis had higher levels of Keap1 expression compared with late-stage tumors (II, III) with the presence of lymphatic metastasis. Colony formation assays showed that Keap1 knockdown promoted the proliferation of A549 and H1299 cells, and the cell growth curves further confirmed this feature. In contrast, wound scratch and transwell invasion experiments showed that Keap1 overexpression inhibited cell migration and invasive malignancy. The IC50 for cisplatin and paclitaxel were significantly increased by Keap1 knockdown in A549 and H1299 cell lines. CONCLUSION: Keap1 knockdown promotes tumor cell growth, proliferation, invasion, metastasis and chemotherapy resistance in LUAD. It may be a potential tumor marker to guide the staging and treatment of lung cancer.