Endoscopic thyroidectomy via chest-collarbone approach versus conventional open thyroidectomy: a retrospective comparative study.

OBJECTIVE(S): Endoscopic thyroidectomy, such as axillary, areola and transoral approaches, offer the advantage of a good cosmetic outcome, but it requires a wider dissection field compared to open thyroidectomy. Recently, chest-collarbone approach thyroidectomy has been widely developed in China because of its shorter anatomical route compared to other endoscopic approaches. This study retrospectively evaluated endoscopic thyroidectomy via chest-collarbone approach in patients with thyroid nodules to determine its feasibility. METHODS: A total of 46 patients with thyroid disease who underwent endoscopic thyroidectomy between January 2022 and December 2022 were enrolled in the study and randomly matched to patients with thyroid disease who underwent open thyroidectomy at the same time based on nodule size and pathology. Postoperative bleeding, hoarseness situation, hospital stay, postoperative drainage volume, laryngeal nerve palsy, hypoparathyroidism and wound infection were assessed in both groups. RESULTS: Forty-four patients underwent endoscopic thyroidectomy successfully and two patients changed to open thyroidectomy. The amount of postoperative drainage for the endoscopic thyroidectomy group was 102.78 ±â€¯28.04 mL, and which was 71.91 ±â€¯19.20 for open thyroidectomy group (p < 0.001). The postoperative hospital stay for the endoscopic thyroidectomy group was 8.78 ±â€¯2.57 days, and which was 7.22 ±â€¯1.13 for open thyroidectomy group (p < 0.001). There was no significant difference in postoperative bleeding, hoarseness situation, and wound infection between the two groups. Laryngeal nerve palsy, supraclavicular nerve injury and hypoparathyroidism were not observed in any patient during this study. CONCLUSION: Chest-collarbone endoscopic thyroid surgery is acceptable. This treatment improves in a good cosmetic outcome in patients with thyroid disease. To assess patients with preoperative nodule size and nature of the case is the impact of the success rate, which is particularly important.

The association between the composite dietary antioxidant index and thyroid functionality among adults in the USA: NHANES 2007-2012.

Objective: Composite Dietary Antioxidant Index (CDAI) values serve as a summary of an individual's combined dietary antioxidant intake. Although specific antioxidants are known to reduce thyroid damage from oxidative stress, the relationship between the CDAI and thyroid function remains uncertain. The purpose of this study was thus to investigate this relationship in greater detail while focusing on a representative American adult population. Methods: A total of 6,860 subjects from the 2007-2012 NHANES cohort were included in this study. Associations between CDAI values and thyroid function were evaluated with weighted linear regression models and smoothed curve fitting. Subgroup analyses were also performed. Results: The weighted mean (SD) values for variables analyzed in this study included a CDAI of 0.13 (0.06), serum free T4 (FT4) levels of 0.80 (0.01) ng/dL, and serum total T4 (TT4) levels of 7.80 (0.03) ug/dL. Lower CDAI values were found to be associated with higher levels of FT4 and TT4 using both unadjusted and adjusted models that accounted for relevant confounders (adjusted model, FT4 ß = -0.003, p = 0.005; TT4 ß = -0.035, p < 0.001). This negative correlation persisted when CDAI was categorized into quartiles (FT4, p for trend = 0.014; TT4, p for trend = 0.003). Conclusion: These findings suggest that a diet rich in antioxidants, as reflected by higher CDAI scores, is associated with significant decreases in levels of free and total T4. Further analyses will be necessary to better clarify the underlying mechanisms behind these observations.

Associations between the platelet/high-density lipoprotein cholesterol ratio and likelihood of nephrolithiasis: a cross-sectional analysis in United States adults.

Aims: The primary objective of this study was to investigate the relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR) and the prevalence of nephrolithiasis within the adult population of the United States. Methods: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. The analysis included a non-pregnant population aged 20 years or older, providing proper PHR index and nephrolithiasis data. The research utilized subgroup analyses and weighted univariate and multivariable logistic regression to evaluate the independent association between the PHR and the susceptibility to nephrolithiasis. Results: The study comprised 30,899 participants with an average PHR value of 19.30 ± 0.11. The overall prevalence rate of nephrolithiasis was estimated at 9.98% with an increase in the higher PHR tertiles (T1, 8.49%; T2, 10.11%; T3, 11.38%, P < 0.0001). An elevated PHR level was closely linked with a higher susceptibility to nephrolithiasis. Compared with patients in T1, and after adjusting for potential confounders in model 2, the corresponding odds ratio for nephrolithiasis in T3 was 1.48 (95% CI: 1.06 to 2.08), with a P-value = 0.02. The results of the interaction tests revealed a significant impact of chronic kidney disease on the relationship between PHR and nephrolithiasis. Furthermore, the restricted cubic spline analyses exhibited a positive, non-linear correlation between PHR and the risk of nephrolithiasis. Conclusion: A convenient biomarker, the PHR, was independently associated with nephrolithiasis and could be a novel biomarker in predicting occurrence in clinical decision.

tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming.

tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5'tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.

The relationship between sleep duration and thyroid function in the adult US population: NHANES 2007-2012.

OBJECTIVE: Sleep disturbance is a common problem in the general population. Sleep deprivation or dysfunction can have profound health consequences. However, how sleep duration is associated with thyroid function remains unclear. This study was thus developed to examine the association between sleep duration and thyroid function in the US adult population. METHODS: A total of 8102 participants from the NHANES 2007-2012 dataset were included in this study. Weighted data analyses were conducted, and the link between sleep duration and thyroid function was probed using linear regression models with smoothed curve fitting. Stratified analyses were also performed. RESULTS: Weighted mean (standard deviation) values for study variables were as follows: sleep duration 6.85 (0.02) hours, thyroid-stimulating hormone (TSH) 1.86 (0.03) mIU/ml, serum free T3 3.20 (0. 01) pg/mL, serum free T4 0.80 (0.01) ng/dL, serum total T3 115.12 (0.64) ng/dL, serum total T4 7.81 (0.04) ug/dL, TPOAb 16.20 (1.53) IU/mL, TgAb 5.75 (0.73) IU/mL, and Tg 15.11 (0.46) ng/mL. In unadjusted analyses, increased sleep duration was associated with higher serum TSH levels and decreased FT3 levels. After adjustment for potential confounders, a significant negative relationship was detected between sleep duration and FT3 levels in participants with ≤7 hours of sleep. When sleep duration exceeded 7 hours, no significant changes in FT3 levels were observed after further increases in sleep duration. CONCLUSION: Increased sleep duration was related to decreased FT3 levels, primarily at short sleep durations, and this correlation was no longer evident when participants reached the recommended healthy sleep duration.

LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage.

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.

Emission characteristics and quantitative assessment of the health risks of cooking fumes during outdoor barbecuing.

Given the increasing popularity of outdoor barbecue activities and the disregard for barbecue fumes, this study systematically investigated barbecue fume emission characteristics for three types of grilled meats. Particulate matter and volatile organic compounds (VOCs) were continuously measured, and polycyclic aromatic hydrocarbons (PAHs) were isolated from the particulate matter. Cooking emission concentrations depended strongly on the type of meat being cooked. Fine particles were the main particles detected in this study. Low and medium-weight PAHs were the dominant species for all cooking experiments. The mass concentration of total VOCs in the barbecue smoke of the three groups showed significant differences (p < 0.05) and was 1667.18 ± 10.49 µg/m3 in the chicken wing group, 904.03 ± 7.12 µg/m3 in the beef steak group, and 3653.37 ± 12.22 µg/m3 in the streaky pork group. The results of risk assessment showed that the toxicity equivalent quality (TEQ) of carcinogenic PAHs in the particulate matter was significantly higher in the streaky pork group than in the chicken wing and beef steak groups. The carcinogenic risk of benzene exceeds the US EPA standard (1.0E-6) in all types of fumes. Although the hazard index (HI) was below one in all groups for noncarcinogenic risks, it was not cause of optimism. We conjecture that only 500 g of streaky pork would exceed the noncarcinogenic risk limit, and the mass required for carcinogenic risk may be less. When barbecuing, it is essential to avoid high-fat foods and strictly control the fat quantity. This study quantifies the incremental risk of specific foods to consumers and will hopefully provide insight into the hazards of barbecue fumes.

Expression and clinical significance of undifferentiated embryonic cell transcription factor 1 in breast cancer.

Background: At present, due to the heterogeneity of breast cancer, common tumor markers have certain limitations in clinical prognostic evaluation. This suggests an unmet need for markers to predict clinical outcomes and potentially guide targeted therapies. The present study sought to explore the expression level and clinical significance of undifferentiated embryonic cell transcription factor 1 (UTF1) in breast cancer. Methods: Immunohistochemistry (IHC) was used to detect the expression of UTF1 in 221 breast cancer samples. The clinical significance of UTF1 protein expression in breast cancer tissues was evaluated by combining clinicopathological parameters and UTF1 expression profile. We performed 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays to evaluate the effect of UTF1 on Bcap37 cell proliferation. Wound healing assay and transwell migration assay were used to evaluate the changes of cell invasion and migration ability, respectively. All experiments were performed with 3 biological replicates. Genomic differences after UTF1 overexpression were evaluated by RNA sequencing technology and the possible functions and regulatory mechanisms were elucidated. Results: The findings showed that UTF1 expression level was significantly correlated with tumor size (P=0.004), but not with patient age, tumor histological stage, lymph node metastasis, as well as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki67 expression levels. Kaplan-Meier survival analysis and Cox proportional hazard model indicated that UTF1 expression was significantly associated with overall survival (OS) time of breast cancer patients. The median survival time of patients with high expression level of UTF1 was shorter compared with that of patients with low UTF1 expression level. The results of cell experiments showed that UTF1 overexpression could significantly promote the growth, proliferation, migration, and invasion of breast cancer cells. The RNA sequencing results showed that UTF1 was not only closely related to apoptosis genes, but also closely related to the nuclear factor (NF)-kappa B pathway. Conclusions: The findings of the current study indicate that UTF1 is involved in occurrence and tumor progression and is significantly associated with prognosis of breast cancer patients.

Inhibition of benzo[a]pyrene formation in charcoal-grilled pork sausages by ginger and its key compounds.

BACKGROUND: Ginger and its extracts have been frequently used in food processing and pharmaceuticals. However, the influence of ginger and its key compounds on benzo[a]pyrene (BaP) production in meat processing has not been investigated. The purpose of this study was to explore the effect of application of ginger and its important active ingredients on BaP formation and the mechanism of inhibiting BaP formation in charcoal-grilled pork sausages. RESULTS: The DPPH scavenging (23.59-59.67%) activity and the inhibition rate of BaP (42.1-68.9%) were significantly increased (P < 0.05) with increasing ginger addition. The active components extracted by supercritical carbon dioxide from ginger were identified by gas chromatography-mass spectrometry and 14 representative compounds (four terpenes, two alcohols, two aldehydes, four phenols and two other compounds, totaling 77.57% of the detected compounds) were selected. The phenolic compounds (eugenol, 6-gingerol, 6-paradol and 6-shogaol, accounting for 29.73% of the total composition) in ginger played a key role and had the strongest inhibitory effect on BaP (61.2-68.2%), whereas four other kinds of compound showed obviously feeble inhibitory activity (6.47-17.9%). Charcoal-grilled sausages with phenolic substances had lower values of thiobarbituric acid-reactive substances, carbonyl and diene (three classic indicators of lipid oxidation) (P < 0.05). CONCLUSION: Ginger and its key compounds could effectively inhibit the formation of BaP in charcoal-grilled pork sausages. Phenolic compounds make the strongest contribution to the inhibition of Bap formation, and the inhibitory mechanism was related to the inhibition of lipid oxidation. © 2023 Society of Chemical Industry.

Insight into the physiological and pathological roles of USP44, a potential tumor target (Review).

Ubiquitin-specific peptidase 44 (USP44) is a member of the ubiquitin-specific proteases (USPs) family and its functions in various biological processes have been gradually elucidated in recent years. USP44 targets multiple downstream factors and regulates multiple mechanisms through its deubiquitination activity. Ubiquitination is, in essence, a process in which a single ubiquitin molecule or a multiubiquitin chain binds to a substrate protein to form an isopeptide bond. Deubiquitination is the catalyzing of the isopeptide bonds between ubiquitin and substrate proteins through deubiquitylating enzymes. These two processes serve an important role in the regulation of the expression, conformation, localization and function of substrate proteins by regulating their binding to ubiquitin. Based on existing research, this paper summarized the current state of knowledge about USP44. The physiological roles of USP44 in various cellular events and its pathophysiological roles in different cancer types are evaluated and the therapeutic potential of USP44 for cancer treatment is evaluated.

COVID-19 induces gastrointestinal symptoms and affects patients' prognosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the pandemic of coronavirus disease 2019 (COVID-19). Gastrointestinal (GI) involvement is common among patients with COVID-19, and GI symptoms can appear earlier than respiratory symptoms. Except for direct infectious effects, patients infected with SARS-CoV-2 are at risk of complications requiring gastroenterological management. Diarrhea is the most common GI symptom in patients with COVID-19 and occurs in up to half of them. Other GI symptoms, such as anorexia, discomfort, nausea, abdominal pain, loss of taste sensation, and vomiting, have been reported. GI symptoms are associated with a poor prognosis. Fecal viral excretion may have clinical significance because of the possible fecal-oral transmission of infection. In the present narrative review article, six different aspects of studies published to date are summarized as follows: GI manifestations of COVID-19, the roles of fecal-oral transmission, poor prognosis of GI symptoms; abnormal abdominal imaging findings, COVID-19 in patients with irritable bowel disease, and prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. Timely understanding of the association between COVID-19 and the digestive system and effective preventive measures are critical to improve this disease and help clinicians take appropriate measures to mitigate further transmission.

Transfer RNA-Derived Small RNAs: Novel Regulators and Biomarkers of Cancers.

Transfer RNA-derived small RNAs (tsRNAs) are conventional non-coding RNAs (ncRNAs) with a length between18 and 40 nucleotides (nt) playing a crucial role in treating various human diseases including tumours. Nowadays, with the use of high-throughput sequencing technologies, it has been proven that certain tsRNAs are dysregulated in multiple tumour tissues as well as in the blood serum of cancer patients. Meanwhile, data retrieved from the literature show that tsRNAs are correlated with the regulation of the hallmarks of cancer, modification of tumour microenvironment, and modulation of drug resistance. On the other side, the emerging role of tsRNAs as biomarkers for cancer diagnosis and prognosis is promising. In this review, we focus on the specific characteristics and biological functions of tsRNAs with a focus on their impact on various tumours and discuss the possibility of tsRNAs as novel potential biomarkers for cancer diagnosis and prognosis.

Expression of 34ßE12 may be an independent predictor of survival in breast cancer.

OBJECTIVES: To investigate the relationship between high-molecular-weight cytokeratin (34ßE12) and clinicopathological parameters (including HER-2, Ki67 and steroid receptors) in breast cancer to determine its usefulness as a prognostic marker. METHODS: In this retrospective study, the expression level 34ßE12 was assessed in surgically resected breast cancer specimens by immunohistochemical staining. Data were correlated with the patients' clinicopathological parameters. RESULTS: Of the 348 breast cancer tissue samples, 232 (67%) showed positive expression of 34ßE12. There were statistically significant differences between the positive and negative 34ßE12 expression groups in tumour size, lymph node involvement, oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status. There were no differences between groups in age, tumour grade, or Ki67 status. In addition, patients who were positive for 34ßE12 had significantly extended overall survival. In multivariate analysis, the expression level of 34ßE12 was found to be a significant independent prognostic factor. CONCLUSION: These results suggest that positive 34ßE12 expression is associated with a favourable outcome in breast cancer and so may be a useful prognostic factor. Further studies are required to confirm these results.

Long non-coding RNA PSMA3-AS1 promotes glioma progression through modulating the miR-411-3p/HOXA10 pathway.

BACKGROUND: Glioma is a common type of brain tumor and is classified as low and high grades according to morphology and molecules. Growing evidence has proved that long non-coding RNAs (lncRNAs) play pivotal roles in numerous tumors or diseases including glioma. Proteasome 20S subunit alpha 3 antisense RNA 1 (PSMA3-AS1), as a member of lncRNAs, has been disclosed to play a tumor-promoting role in cancer progression. However, the role of PSMA3-AS1 in glioma remains unknown. Therefore, we concentrated on researching the regulatory mechanism of PSMA3-AS1 in glioma. METHODS: PSMA3-AS1 expression was detected using RT-qPCR. Functional assays were performed to measure the effects of PSMA3-AS1 on glioma progression. After that, ENCORI ( http://starbase.sysu.edu.cn/ ) database was used to predict potential genes that could bind to PSMA3-AS1, and miR-411-3p was chosen for further studies. The interaction among PSMA3-AS1, miR-411-3p and homeobox A10 (HOXA10) were confirmed through mechanism assays. RESULTS: PSMA3-AS1 was verified to be up-regulated in glioma cells and promote glioma progression. Furthermore, PSMA3-AS1 could act as a competitive endogenous RNA (ceRNA) for miR-411-3p to regulate HOXA10 and thus affecting glioma progression. CONCLUSION: PSMA3-AS1 stimulated glioma progression via the miR-411-3p/HOXA10 pathway, which might offer a novel insight for the therapy and treatment of glioma.

Impact of Lin28 on lymph node metastasis in papillary thyroid carcinoma.

Lin28 is involved in the progression of several types of tumors. Data collected from clinical trials have suggested that Lin28 expression is correlated with poor prognosis in thyroid carcinoma. The present study was conducted to investigate the association between Lin28 expression and the clinicopathological parameters of papillary thyroid carcinoma (PTC). Accordingly, the clinical data and diagnostic results from 237 patients with PTC were collected. Immunohistochemical staining was performed to evaluate the Lin28 expression levels in thyroid tissue samples. Associations between the expression levels and clinicopathological parameters were evaluated. Lin28 was expressed in 96/237 (40.5%) of PTC specimens. Compared with patients with no Lin28 expression, patients with expression had higher rates of lymph node metastasis (P<0.001) and larger tumors (P=0.011). Multivariate analysis revealed that Lin28 was associated with lymph node metastasis. Next, bioinformatics analysis was performed based using the Gene Expression Omnibus database and The Cancer Genome Atlas database. Lin28 expression was associated with aggressive tumor characteristics, such as lymph node metastasis and larger tumors. In conclusion, the present study revealed that Lin28 expression served as a risk factor for lymph node metastasis. Accordingly, Lin28 expression may be used as a prognostic marker to predict lymph node metastasis in patients with PTC. In addition, Lin28 may serve as a therapeutic target in the management of this tumor type, which may help improve patient outcomes.

Treatment of esophageal cancer with multiple liver metastases: a case experience of sustained complete response.

Esophageal squamous cell cancer with distant metastases has a poor prognosis. The metastatic sites usually involve the liver, bones, and lungs. Treatment of metastatic disease is essentially palliative and based on chemoradiotherapy. A 57-year-old man with a solitary metastatic mass of 82 × 58 mm in the left liver was treated on 19 October 2012. Irinotecan and cisplatin combination chemotherapy and nimotuzumab targeted therapy were administered. The liver metastatic mass was treated by stereotactic Gamma Knife radiosurgery. Complete remission of the primary disease and hepatic lesion was achieved, and no local or distant recurrence was found during the 7-year follow-up. Because extrahepatic lesions were ruled out and the local disease was completely locoregionally controlled, the use of stereotactic Gamma Knife radiosurgery to remove the hepatic lesion was justified and produced a reasonable outcome.

Management of a metal foreign body entering the thyroid via the esophagus: a case report.

The entry of a metallic foreign body into the thyroid gland via the esophagus is a rare occurrence, with no previously reported cases. We present a 42-year-old woman who was admitted to hospital with right-sided neck pain, reporting that she had inadvertently swallowed a fish bone. She underwent laryngoscopy, which showed no fish bone in the throat, and no obvious bleeding in the bilateral tonsils and pear-shaped fossa. X-ray examination showed a needle-shaped foreign body in the neck, and a computed tomography scan of her neck showed a 0.1-cm diameter, 2.0-cm long foreign body in the right thyroid. She underwent emergency surgery and a needle of the corresponding size was found in the thyroid gland. This case demonstrates the importance of adequate preoperative assessment and an appropriate surgical approach for thyroid metallic foreign bodies.

Expression of Lin28 is correlated with prognosis and expression of HER-2 and steroid receptors in breast cancer.

OBJECTIVE: Cumulative data from clinical trials suggest that Lin28 may contribute to poor survival in breast cancer patients. The purpose of this study was to investigate the relationship between Lin28 expression and breast cancer patients' clinicopathological parameters. METHODS: Data from a total of 291 breast cancer patients were collected in this study. The expression level of Lin28 was assessed by immunohistochemical staining. The correlation of Lin28 expression and clinicopathological parameters was statically evaluated and the prognostic significance of Lin28 expression was assessed by univariate and multivariate analyses. RESULTS: One hundred and eight out of 291 (37.1%) breast cancer specimens showed Lin28 protein positive expression, while the remaining 183 specimens showed negative expression. Positive expression of Lin28 was associated with lymph node metastases (P<0.001), HER-2 (P=0.024), estrogen receptor (P=0.039), and progesterone receptor (P=0.027). Kaplan-Meier analysis showed that Lin28 positive expression showed lower overall survival rates compared with Lin28 negative patients (P=0.019). In the multivariate analysis, Lin28 remained a significant independent prognostic factor (P=0.038) for overall survival rates. CONCLUSION: Lin28 expression was associated with advanced disease stage and subtype in breast cancer patients, and Lin28 expression may serve as an independent prognostic factor. These data indicate that Lin28 may play a major role in the therapeutic management of breast cancer.

LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis.

The long non-coding RNA HOXA-AS2 has been found to be an oncogene in several types of human malignant tumors. However, its role in regulating the occurrence and development of papillary thyroid cancer (PTC) is still unclear. The present study investigated the function and mechanism(s) of HOXA-AS2 in PTC progression. Using quantitative real-time polymerase chain reaction, HOXA-AS2 was found to be differentially expressed in PTC tissues and cell lines. Kaplan-Meier analysis indicated that the overall survival rate of patients with higher levels of HOXA-AS2 was lower than those with relatively lower levels. Loss-of-function assays revealed that HOXA-AS2 knockdown inhibited PTC progression by inhibiting cellular proliferation, migration, and invasion and accelerating apoptosis. Mechanistically, loss-of-function assays showed a positive correlation between HOXA3 and HOXA-AS2 expression. Subcellular fractionation assay results revealed abundant HOXA-AS2 expression in the cytoplasm of PTC cells. Additionally, FOXD2-AS1 was found to upregulate HOXA3 expression by binding to miR-15a-5p. Finally, rescue assays demonstrated the overall function of the HOXA-AS2/miR-15a-5p/HOXA3 axis in PTC progression. These findings will significantly contribute to further research and the development of more efficient treatments for thyroid cancer in the future.

Roles of endoplasmic reticulum stress and autophagy on H2O2­induced oxidative stress injury in HepG2 cells.

Endoplasmic reticulum stress (ERS) can be induced by a variety of physiological and pathological factors including oxidative stress, which triggers the unfolded protein response to deal with ERS. Autophagy has been hypothesized to be a means for tumor cells to increase cell survival under conditions of hypoxia, metabolic stress and even chemotherapy. Although they may function independently from each other, there are also interactions between responses to oxidative stress injury induced by pathologic and pharmacological factors. The aim of the present study was to investigate the effects of ERS and autophagy on H2O2­induced oxidative stress injury in human HepG2 hepatoblastoma cells. It was demonstrated that exposure of HepG2 cells to H2O2 decreased cell viability and increased reactive oxygen species (ROS) levels in a dosage­dependent manner. In addition, apoptosis and autophagy rates were elevated and reduced following cell exposure to H2O2 + the ERS inducer Tunicamycin (TM), and to H2O2 + the ERS inhibitor Salubrinal (SAL), compared with the cells treated with H2O2 alone, respectively. Further studies revealed that TM enhanced the expression of ERS­related genes including glucose­regulated protein­78/binding immunoglobulin protein, inositol­requiring kinase­I and activating transcription factor 6 and C/EBP­homologous protein 10, which were attenuated by SAL compared with cells exposed to H2O2 alone. The data from the present study also demonstrated that LC3II/LC3­I and p62, members of autophagy­related genes, were increased and decreased in cells treated with H2O2 + TM compared with cells treated with H2O2, respectively, indicating that autophagy was stimulated by ERS. Furthermore, a reduction in the levels of pro caspase­3 and pro caspase­9, and elevation level of caspase­12 were observed in cells exposed to H2O2 + TM compared with cells treated with H2O2, respectively, suggesting apoptosis induced by H2O2 was enhanced by ERS or autophagy triggered by H2O2. The above results suggest that the ERS inducer may be a potential target for pharmacological intervention targeted to ERS or autophagy to enhance oxidative stress injury of tumor cells induced by antitumor drugs.