Flavopereirine exerts anti-cancer activities in various human thyroid cancer cells.

Thyroid cancer (TC) stands out as the most prevalent endocrine malignancy globally, with a steadily increasing incidence. Its clinical manifestations include enlarged thyroid nodules, dysphagia, enophthalmos, and various other symptoms. While standard treatments such as thyroidectomy and radioiodine therapy effectively manage most cases of differentiated thyroid cancers (DTC), some recurrent cases of DTC or those involving poorly differentiated thyroid cancers (PDTC) require specialized interventions. However, existing drugs primarily address symptom management without offering a curative solution. Therefore, the development of a new therapeutic agent for these challenging cases is of utmost importance. Flavopereirine, derived from Geissospermum vellosii, has demonstrated promise as a potential anti-cancer agent across various human cancers. However, its specific anti-cancer effects on human thyroid cancer (TC) have remained unclear. Therefore, this study aims to investigate the anti-cancer activity of flavopereirine in human TC. The research findings revealed that flavopereirine effectively hinders the growth of human TC cells, induces cell cycle arrest, promotes apoptosis, and modulates autophagy. Moreover, the study delved into the underlying mechanisms by which flavopereirine influenced signaling pathways. To validate these anti-cancer effects, an in vivo zebrafish model was utilized, confirming the efficacy of flavopereirine against human TC cells. In summary, this study establishes that flavopereirine exhibits notable anti-human TC activities, positioning it as a promising therapeutic candidate for the treatment of human thyroid cancer.

Chlorpyrifos-induced suppression of the antioxidative defense system leads to cytotoxicity and genotoxicity in macrophages.

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.

Development and Validation of a 3D Resnet Model for Prediction of Lymph Node Metastasis in Head and Neck Cancer Patients.

The accurate diagnosis and staging of lymph node metastasis (LNM) are crucial for determining the optimal treatment strategy for head and neck cancer patients. We aimed to develop a 3D Resnet model and investigate its prediction value in detecting LNM. This study enrolled 156 head and neck cancer patients and analyzed 342 lymph nodes segmented from surgical pathologic reports. The patients' clinical and pathological data related to the primary tumor site and clinical and pathology T and N stages were collected. To predict LNM, we developed a dual-pathway 3D Resnet model incorporating two Resnet models with different depths to extract features from the input data. To assess the model's performance, we compared its predictions with those of radiologists in a test dataset comprising 38 patients. The study found that the dimensions and volume of LNM + were significantly larger than those of LNM-. Specifically, the Y and Z dimensions showed the highest sensitivity of 84.6% and specificity of 72.2%, respectively, in predicting LNM + . The analysis of various variations of the proposed 3D Resnet model demonstrated that Dual-3D-Resnet models with a depth of 34 achieved the highest AUC values of 0.9294. In the validation test of 38 patients and 86 lymph nodes dataset, the 3D Resnet model outperformed both physical examination and radiologists in terms of sensitivity (80.8% compared to 50.0% and 91.7%, respectively), specificity(90.0% compared to 88.5% and 65.4%, respectively), and positive predictive value (77.8% compared to 66.7% and 55.0%, respectively) in detecting individual LNM + . These results suggest that the 3D Resnet model can be valuable for accurately identifying LNM + in head and neck cancer patients. A prospective trial is needed to evaluate further the role of the 3D Resnet model in determining LNM + in head and neck cancer patients and its impact on treatment strategies and patient outcomes.

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways.

Cyclizine, an over-the-counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine-induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V-fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC-1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor-α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration-dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration-dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.

Outcome of Thromboembolic Events and Its Influence on Survival Time of Advanced NSCLC Patients Treated with Antiangiogenic Therapy.

Background: Antiangiogenetic therapy and lung cancer, per se, are associated with an increased risk of thromboembolic events (TE). We aim to evaluate the pattern and outcome of TE as well as its influence on survival time of advanced non-small cell lung cancer (NSCLC) patients receiving antiangiogenic therapy. Methods: This was a retrospective cohort study, which included advanced NSCLC patients receiving antiangiogenic therapy. All TE were confirmed by objective image studies. We disclosed the presentation and risk factors of TE and evaluated its influence on outcome. Results: A total of 427 patients were included. TE occurred in 43 patients (10.1%). Deep vein thrombosis (DVT) was the most common TE (n = 20). Up to 46.2% of DVT did not occur in the typical lower extremities. Two patients died of TE. Among patients with continuous use or reuse of antiangiogenetic therapy, 18.2% had recurrent TE events. At the occurrence of TE, 28 patients experienced progressive disease (TE with PD), while tumor status remained stable in another 15 patients (TE without PD). The post-TE survival of patients without and with PD were 8.9 months (95% CI 3.9-13.9) vs 2.2 months (95% CI 0.1-4.3), P = 0.012. As compared with patients without TE (31.4 months [95% CI 27.1-35.7]), TE with PD patients experienced a significantly shorter overall survival (20.1 months [95% CI 15.5-24.6]), but TE without PD patients had comparable survival time (32.7 months [95% CI 7.4-28.1]) (P = 0006). The use of hormone analogue and proteinuria predicted the events among TE with PD group (aOR 2.79 [95% CI 1.13=6.92]; P = 0.027) and TE without PD group (aOR 4.30 [95% CI 1.13-16.42]; P = 0.033), respectively. Conclusion: Owing to the different risk factors and influences on the survival time, TE with and without PD may be two different disease entities.

Reactivation of Hepatitis B Virus in Lung Cancer Patients Receiving Tyrosine Kinase Inhibitor Treatment.

(1) Background: We aimed to evaluate the risk of hepatitis B virus (HBV) reactivation in lung cancer patients treated with tyrosine kinase inhibitor (TKI), particularly in those with resolved HBV infection. (2) Methods: In this retrospective hospital-based cohort study, we screened all lung cancer patients with positive hepatitis B core antibodies (anti-HBc) receiving systemic antineoplastic treatment during the period from January 2011 to December 2020. Cumulative incidences of HBV reactivation, and their hazard ratios (HRs), were evaluated after adjusting patient mortality as a competing risk. (3) Results: Among 1960 anti-HBc-positive patients receiving systemic therapy, 366 were HBsAg-positive and 1594 were HBsAg-negative. In HBsAg-positive patients without prophylactic NUC, 3-year cumulative incidences of HBV reactivation were similar between patients receiving chemotherapy and patients receiving TKI (15.0%, 95% confidence interval (CI): 0−31.2% vs. 21.2%, 95% CI: 10.8−31.7%; p = 0.680). Likewise, 3-year cumulative incidences of HBV-related hepatitis were similar between the two groups (chemotherapy vs. TKI: 15.0%, 95% CI: 0−31.2% vs. 9.3%, 95% CI: 2.8−15.7%; p = 0.441). In 521 HBsAg-negative TKI users, the 3-year cumulative incidence of HBV reactivation was only 0.6% (95% CI: 0.0−1.9%). From multivariable regression analysis, we found that the only independent risk factor for HBV reactivation in TKI users was HBsAg positivity (HR 53.8, 95% CI: 7.0−412.9; p < 0.001). (4) Conclusion: Due to high risks of HBV reactivation in HBsAg-positive TKI users, NUC prophylaxis can be considered. However, in patients with resolved HBV infection, such risks are lower, and therefore regular monitoring is recommended.

Enhanced Sensing Ability of Brush-Like Fe2O3-ZnO Nanostructures towards NO2 Gas via Manipulating Material Synergistic Effect.

Brush-like α-Fe2O3-ZnO heterostructures were synthesized through a sputtering ZnO seed-assisted hydrothermal growth method. The resulting heterostructures consisted of α-Fe2O3 rod templates and ZnO branched crystals with an average diameter of approximately 12 nm and length of 25 nm. The gas-sensing results demonstrated that the α-Fe2O3-ZnO heterostructure-based sensor exhibited excellent sensitivity, selectivity, and stability toward low-concentration NO2 gas at an optimal temperature of 300 °C. The α-Fe2O3-ZnO sensor, in particular, demonstrated substantially higher sensitivity compared with pristine α-Fe2O3, along with faster response and recovery speeds under similar test conditions. An appropriate material synergic effect accounts for the considerable enhancement in the NO2 gas-sensing performance of the α-Fe2O3-ZnO heterostructures.

Case history on Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) of cranio-cervical junction in an immunocompetent patient.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor that almost exclusively occurs in immunocompromised hosts. Here, we report a 75-year-old Taiwanese woman without definite immune-deficient history presenting with progressive occipital neuralgia, low cranial nerve deficits (CN9-12) and cervical (C1-C5) radiculopathy. Magnetic resonance imaging revealed a 4.5*4.0*6.7 cm infiltrating mass occupying posterior skull base and C1-C2 vertebra and C1-5 epidural extension with bone destruction and vertebral artery (VA) encasement. There was also a synchronous 2.7 cm tonsillar tumor. A two-stage operation for cranio-cervical tumor excision and stabilization was performed. Tumor was confirmed directly arising from VA intraoperatively. Pathology reported a spindle cell neoplasm and the diagnosis of EBV-SMT was confirmed by EBER (EBV-encoded small RNA) in situ hybridization. An immune survey and reconstruction should be conducted for patient with EBV-SMT. A near-total resection of tumor may be beneficial for local control, however, the role of surgical resection in treating CNS EBV-SMT remains to be determined.

Role of surgery in treating epstein-barr virus-associated smooth muscle tumor (EBV-SMT) with central nervous system invasion: A systemic review from 1997 to 2019.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor occurred almost exclusively in immunocompromised hosts. This article provides a systematic review of literature under PRISMA guideline on clinical features, treatment modalities, roles of surgical intervention, and outcomes of all 65 reported EBV-SMTs with central nervous system (CNS) invasion. Over 95% of reported cases were immunocompromised, while human immunodeficiency virus infection and post-organ transplantation were the most commonly associated underlying causes (near 90%). Despite a heterogeneous follow-up period, a 1-year survival rate of 76.0% and 5-year survival rate of 59.6% may support the indolent and non-deadly nature of EBV-SMT even with CNS invasion. Immune survey and reconstruction should be conducted for every patient with CNS EBV-SMT. Surgical resection is mostly adopted as primary treatment to obtain diagnosis and relieve compressive effect. A total resection of tumor may be beneficial if tumor was symptomatic and had intracranial invasion.

Biomarker discovery in highly invasive lung cancer cell through proteomics approaches.

Lung cancer is one of the leading causes of cancer-related death worldwide. The most common type of lung cancer is non-small cell lung cancer (NSCLC). When NSCLC is detected, patients are typically already in a metastatic stage. Metastasized cancer is a major obstacle of effective treatment and understanding the mechanisms underlying metastasis is critical to treat cancer. Herein, we selected an invasive subpopulation from the human lung cancer cell line A549 using the transwell system and named it as A549-I5. Invasive and migratory activities of this cell line were analysed using wound healing, invasion, and migration assays. In addition, epithelial-mesenchymal transition (EMT) markers, such as Snail 1, Twist, Vimentin, N-cadherin and E-cadherin, were assessed through immunoblotting. In comparison to A549 cells, the invasive A549-I5 lung cancer cells had enhanced invasiveness, motility and EMT marker expression. Proteomic analysis identified 83 significantly differentially expressed proteins in A549-I5 cells. These identified proteins were classified according to their cellular functions and most were involved in cytoskeleton, redox regulation, protein degradation and protein folding. In summary, our results provide potential diagnostic markers and therapeutic candidates for the treatment of NSCLC metastasis. SIGNIFICANCE OF THE STUDY: When NSCLC is detected, most patients are already in a metastatic stage. Herein, we selected an invasive subpopulation from a human lung cancer cell line which had increased EMT markers as well as high wound healing, invasion and migration abilities. Proteomic analysis identified numerous proteins associated with functions in cytoskeleton, redox regulation, protein degradation and protein folding that were differentially expressed in these cells. These results may provide potential diagnostic markers and therapeutic candidates for the treatment of NSCLC metastasis.

Refractory Facial Paralysis: A Case Report.

PURPOSE: To present a case of salivary gland malignancy initially mimicking Bell's palsy. CASE REPORT: A 75-year-old woman with hypertension visited our neurological outpatient department,complaining of persistent right facial paralysis for more than a year after oral glucocorticoid therapy with recent development of vertigo and unsteady gait. She was previously diagnosed as having Bell's palsy and was prescribed oral glucocorticoid. However, her right facial muscles were still completely paralyzed, with no signs of improvement. The patient visited the outpatient department of neurology for 3 weeks, seeking treatment for the recent onset of vertigo and ataxia. Brain contrast magnetic resonance imaging (MRI) revealed the right mastoid air cells to be filled with high T2 signal intensity and low T1 signal, with destruction of the bony structure of mastoid, extending to the right jugular bulb. Results obtained from excisional biopsy and pathological analyses were used to diagnose the patient with adenoid cystic carcinoma of the salivary gland. The patient then received a thorough cancer workup and chemoradiotherapy, with the malignancy being under control. However, after a 1-year follow-up, the patient still had permanent right facial palsy. CONCLUSION: Salivary gland malignancy should be considered in patients with acute and subacute facial nerve paralysis, in addition to Bell's palsy. Brain imaging with contrast agents should be performed for differential diagnosis.

Associations Between Sleep Quality and Migraine Frequency: A Cross-Sectional Case-Control Study.

Migraine has been associated with sleep disturbances. Relationship between sleep quality and migraine frequency is yet to be determined. The present study aimed to investigate sleep disturbances among low-frequency, moderate-frequency, high-frequency, and chronic migraineurs, with and without auras, with well-controlled confounding variables.This cross-sectional controlled study included 357 subjects from an outpatient headache clinic in Taiwan. Standardized questionnaires were utilized to collect demographic, migraine, sleep, depression, anxiety, and restless leg syndrome characteristics in all participants. According to frequency of migraine attacks, patients were divided into 4 groups: with 1 to 4 migraine days per month, 5 to 8 migraine days in a month, 9 to 14 migraine days in a month, and >14 migraine days per month. The Pittsburgh Sleep Quality Index (PSQI) and subgroup items were used to evaluate sleep quality. The association between migraine frequency and sleep quality was investigated using multivariable linear regression and logistic regression.The PSQI total score was highest in patients with high frequent migraine (10.0 ±â€Š3.4) and lowest in controls (7.0 ±â€Š3.4) with a significant trend analysis (P for trend = 0.006). Migraine frequency had an independent effect on the items "Cannot get to sleep within 30 minutes" (P < 0.001), "Wake up in the middle of the night or early morning" (P < 0.001), "Bad dreams" (P = 0.001), "Pain" (P = 0.004), and "Quality of sleep" (P < 0.001). The result showed the effect of migraine frequency in both the aura-present (P for trend = 0.008) and the aura-absent subgroups (P for trend = 0.011).High migraine frequency correlates with poor sleep quality and a higher prevalence of poor sleepers. These associations occur in migraine with aura and without aura.

Automatic slice selection and diagnosis of breast strain elastography.

PURPOSE: Generally speaking, breast imaging experts and physicians select a representative slice from the strain elastographic image sequences to diagnose the tumor. Given the strain image qualities, it is difficult to make a successful diagnosis using human eyes only. The main purpose of this study is to develop an automatic and reliable method to select the representative slice from the elastography cine loops and/or video and then diagnose the tumor by means of the elastographic features generated from the selected slice. METHODS: In this study, the authors collected 80 biopsy-proven breast tumors, comprising of 45 benign and 35 malignant lesions, to estimate the performance of the automatic slice selection method. Images chosen using several slice selection criteria (e.g., whole-image analysis or tumor region analysis) were compared to the physician-selected images to determine the best selection criterion. The level set tumor segmentation method was applied to the corresponding B-mode part of the representative elastographic slice to overlap tumor boundaries on strain images and to calculate elastographic features for diagnosis. RESULTS: The experiment showed that the diagnostic performance, in terms of accuracy, sensitivity, and specificity, evaluated by the leave-one-out method, based on the elastographic features for the representative slice selected by the proposed slice selection method, was 71.3%, 91.4%, and 55.6%, respectively, while the performance values for the physician-selected slice were 65.0%, 77.1%, and 55.6%, respectively. CONCLUSIONS: Both the sensitivity and accuracy of the proposed slice selection method were better than those of the physician-selected slice, and the specificity of these two different schemes is similar. According to the statistical analysis of experimental results, the performance of the proposed slice selection method was similar to that of the physician's selection. The authors concluded that the proposed slice selection method could assist the physician in selecting the appropriate representative slice and in decreasing the time of selection.

Zero-valent iron reduction of nitrate in the presence of ultraviolet light, organic matter and hydrogen peroxide.

This paper describes the use of metallic iron (Fe(0)) powder for nitrate removal in a well-mixed batch reactor. Important variables explored include Fe(0) dosage (1-3g/L), UV light intensity (64-128 W), and the presence of propanol (20 mg/L as DOC) and H(2)O(2) (100-200 mg/L). Accumulation of ferrous ions released from the Fe(0) surface can be expressed by an S-curve, which involves lag growth phase, exponential phase, rate-declining phase, and saturation phase. The removal of nitrate increases with increasing Fe(0) dosage; however, the removal makes no difference as the Fe(0) dosage is greater than 2 g/L. UV irradiation retards the dissolution of ferrous ion and the removal of nitrate. The species of propanol, which has a functional group of -OH, plays a role of organic inhibitor for Fe(0) corrosion. The presence of H(2)O(2) appears to inactivate all reactions as the Fe(0) of 10 microm was used; the final H(2)O(2) remains intact throughout the entire reaction period, and there were no removal of nitrate and no dissolution of ferrous ion. Surprisingly, with the use of a larger Fe(0) particle size of 150 microm, the H(2)O(2) was seen to decompose rapidly through Fenton reaction. Nevertheless, the rate of ferrous accumulation or nitrate removal is slow.