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Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.
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In primary hyperparathyroidism, postoperative hypocalcemia can be exacerbated by magnesium deficiency. However, the significance of magnesium homeostasis in surgery for secondary hyperparathyroidism is unknown. In this study, 268 consecutive adult patients on renal replacement therapy who underwent parathyroidectomy for secondary hyperparathyroidism were included for analysis. We found that about one fifth presented with hypomagnesemia (5.6%) or hypermagnesemia (14.6%). Hypomagnesemia was associated with lower calcium levels and longer postoperative hospital stays. Hypermagnesemia was associated with higher calcium-phosphorus products and lower parathyroid hormone levels. In multivariate analysis, patient age, alkaline phosphatase, and osteocalcin were independent predictors of prolonged stay after parathyroidectomy. There was a positive correlation between serum magnesium levels and severity of itching in these patients. Calcium-phosphorus products and serum magnesium levels were independently associated with pruritus. In conclusion, magnesium abnormalities play a minor role in hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism. Patients with higher serum magnesium levels had greater severity of pruritus.
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Although trans-vaginal mesh (TVM) offers a successful anatomical reconstruction and can subjectively relieve symptoms/signs in pelvic organ prolapse (POP) patients, its objective benefits to the voiding function of the bladder have not been well established. In this study, we investigated the therapeutic advantage of TVM on bladder function by focusing on the thermodynamic workload of voiding. The histories of 31 POP patients who underwent TVM repair were retrospectively reviewed. Cystometry and pressure volume analysis (PVA) of the patients performed before and after the operation were analyzed. TVM postoperatively decreased the mean voiding resistance (mRv, p < 0.05, N = 31), reduced the mean and peak voiding pressure (mPv, p < 0.05 and pPv, p < 0.01, both N = 31), and elevated the mean flow rate (mFv, p < 0.05, N = 31) of voiding. While displaying an insignificant effect on the voided volume (Vv, p < 0.05, N = 31), TVM significantly shortened the voiding time (Tv, p < 0.05, N = 31). TVM postoperatively decreased the loop-enclosed area (Apv, p < 0.05, N = 31) in the PVA, indicating that TVM lessened the workload of voiding. Moreover, in 21 patients who displayed postvoiding urine retention before the operation, TVM decreased the residual volume (Vr, p < 0.01, N = 21). Collectively, our results reveal that TVM postoperatively lessened the workload of bladder voiding by diminishing voiding resistance, which reduced the pressure gradient required for driving urine flow.
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PURPOSE: Dendritic cell infiltrates are increased in thyroid cancer but may have a defective ability to provoke effective immune responses. In this study, we aimed to identify potential thyroid cancer biomarkers linked to dendritic cell development and evaluate their prognostic relevance. METHODS: Through a bioinformatics search, we identified the dendrocyte-expressed seven transmembrane protein (DCSTAMP) as a prognostic gene involved in dendritic cell differentiation for thyroid cancer. Immunohistochemical analyses of DCSTAMP expression were performed and correlated with clinical outcomes. RESULTS: DCSTAMP was overexpressed in a variety of types of thyroid cancers, while normal thyroid tissue or benign thyroid lesions exhibited low or undetectable DCSTAMP immunoreactivity. The results of automated quantification were consistent with subjective semiquantitative scoring. Among 144 patients with differentiated thyroid cancer, high DCSTAMP expression was associated with papillary tumor type (p < 0.001), extrathyroidal extension (p = 0.007), lymph node metastasis (p < 0.001), and BRAF V600E mutation (p = 0.029). Patients with tumors showing high DCSTAMP expression had shorter overall (p = 0.027) and recurrence-free (p = 0.042) survival. CONCLUSION: This study provides the first evidence of DCSTAMP overexpression in thyroid cancer. Apart from the prognostic implications, studies are needed to explore its potential immunomodulatory role in thyroid cancer.
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Adenocarcinoma , Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Carcinoma Papilar/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/patología , Regulación hacia ArribaRESUMEN
Neovascular age-related macular degeneration (AMD) is described as abnormal angiogenesis in the retina and the leaking of fluid and blood that generates a huge, dark, blind spot in the center of the visual field, causing severe vision loss in over 90% of patients. Bone marrow-derived endothelial progenitor cells (EPCs) contribute to pathologic angiogenesis. Gene expression profiles downloaded from the eyeIntegration v1.0 database for healthy retinas and retinas from patients with neovascular AMD identified significantly higher levels of EPC-specific markers (CD34, CD133) and blood vessel markers (CD31, VEGF) in the neovascular AMD retinas compared with healthy retinas. Melatonin is a hormone that is mainly secreted by the pineal gland, and is also produced in the retina. Whether melatonin affects vascular endothelial growth factor (VEGF)-induced EPC angiogenesis in neovascular AMD is unknown. Our study revealed that melatonin inhibits VEGF-induced stimulation of EPC migration and tube formation. By directly binding with the VEGFR2 extracellular domain, melatonin significantly and dose-dependently inhibited VEGF-induced PDGF-BB expression and angiogenesis in EPCs via c-Src and FAK, NF-κB and AP-1 signaling. The corneal alkali burn model demonstrated that melatonin markedly inhibited EPC angiogenesis and neovascular AMD. Melatonin appears promising for reducing EPC angiogenesis in neovascular AMD.
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Células Progenitoras Endoteliales , Melatonina , Degeneración Macular Húmeda , Humanos , Inhibidores de la Angiogénesis , Factor A de Crecimiento Endotelial Vascular , Agudeza VisualRESUMEN
While an increasing number of patients now undergo lobectomy for low-risk differentiated thyroid cancer, a subset of patients require completion thyroidectomy to facilitate radioactive iodine therapy. Completion thyroidectomy is generally as safe as the initial operation, but a previous study showed that a longer hospitalization is required for completion thyroidectomy. In this study, we reviewed 61 consecutive patients who had been treated with an initial lobectomy and subsequent completion thyroidectomy at our institution from 2012 to 2021. We detected a changepoint in 2016 for the proportion of patients who were treated with a thyroid lobectomy (Pettitt's test P = 0.049). The rate of completion thyroidectomy remained stable throughout the study period. There was no difference in operating time, intraoperative blood loss, perioperative drop in calcium levels, and postoperative hospital stay between surgeries. The patients reported higher pain scores on the day of operation (P = 0.007) and the postoperative day 1 (P = 0.022). Occult papillary microcarcinomas were identified in the contralateral thyroid lobe in 13 (21%) patients. Multifocality was the only predictor for residual malignancy in multivariate regression. In conclusion, patients with differentiated thyroid cancer experienced more pain in the immediate postoperative period following completion thyroidectomy. Hospital stays do not change with appropriate opioid-free pain control.
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Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Tiroidectomía , Radioisótopos de Yodo , Adenocarcinoma/cirugía , Periodo Posoperatorio , Dolor , Estudios RetrospectivosRESUMEN
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human HCC cells. In this study, we found that cryptocaryone potently induced growth inhibition by apoptotic cell death in HCC cells. Cryptocaryone also suppressed the ATP synthesis, lactate production and glycolytic capacity of HCC cells. Mechanistic investigations showed that phosphorylation of Akt and c-Src, as well as the expression of HK1 were impeded by cryptocaryone. Moreover, cryptocaryone markedly increased the expression level of transcription factor FoxO1. Importantly, clinical database analysis confirmed the negative correlation between HK1 and FoxO1. High expression levels of HK-1 were positively correlated with poorer survival in patients with HCCs. These results suggest that cryptocaryone may promote cell apoptosis by inhibiting FoxO1-mediated aerobic glycolysis through Akt and c-Src signaling cascades in human HCC cells. This is the first study to indicate that cryptocaryone exerts anti-cancer property against human HCC cells. Cryptocaryone is a potential natural product worthy of further development into a promising candidate for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Pironas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Transducción de Señal , Glucólisis , ApoptosisRESUMEN
Importance: It needs to be clarified whether trans-obturator tape (TOT)-enhanced urethral resistance could impact the voiding function. Objective: Although TOT has been well-recognized for enhancing urethral resistance to restore continence in stress urinary incontinence (SUI) patients, whether the bladder's voiding functions adapt to the TOT-enhanced resistance has not been adequately investigated. This study thereby aimed to investigate whether TOT impacts the bladder's thermodynamic efficacy during the voiding phase. Design: A retrospective analysis of urodynamics performed before and after TOT was assessed. Setting: A tertiary referral hospital in Taiwan. Participants: A total of 26 female SUI patients who underwent urodynamic investigations before and after TOT. Main outcomes and measures: The area enclosed by the pressure-volume loop (Apv), which represents the work performed by the bladder during voiding, in a pressure-volume analysis established by plotting the detrusor pressure versus intra-vesical volume was retrospectively analyzed. Paired Student's t-tests were employed to assess the difference in values before and after the operation. Significance in difference was set at p < 0.05. Results: TOT increased Apv in 20 of 26 (77%) patients and significantly increased the mean Apv compared to the preoperative control (2.17 ± 0.18 and 1.51 ± 0.13 × 103 cmH2O-ml, respectively p < 0.01). TOT also increased the mean urethral resistance (1.03 ± 0.30 vs. 0.29 ± 0.05 cmH2O-sec/ml, p < 0.01) and mean voiding pressure (25.87 ± 1.72 and 19.30 ± 1.98 cmH2O p < 0.01) but did not affect the voided volume and voiding time. Moreover, the TOT-induced Apv increment showed a moderate correlation with the changes in urethral resistance and voiding pressure (both r > 0.5) but no correlation with changes in voided volume or voiding time. It is remarkable that the TOT-induced urethral resistance increment showed a strong correlation with changes in voiding pressure (r > 0.7). Conclusion and Relevance: The bladder enhances thermodynamic efficacy by adapting the voiding mechanism to increased urethral resistance caused by TOT. Further studies with higher case series and longer follow-ups should assess whether this effect could be maintained over time or expire in a functional detrusor decompensation, to define diagnostic criteria that allow therapeutic interventions aimed at its prevention during the follow-up. Clinical Trial Registration: (clinicaltrials.gov), identifier (NCT05255289).
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BACKGROUND/AIM: Expression of sterol regulatory element-binding protein 1 (SREBP1) is upregulated in thyroid cancer and associated with shorter disease-specific survival. The molecular regulatory mechanisms governing SREBP1 over-expression in thyroid cancer are still unclear. MATERIALS AND METHODS: Thyroid cancer cell lines BHT-101 (with the BRAF V600E mutation) and FTC-131 (wild-type for BRAF) were treated with specific inhibitors. The expression of SREBP1 was determined at the mRNA level using quantitative real-time PCR and at the protein level using immunoblotting. RESULTS: Lenvatinib and a MEK inhibitor, selumetinib, suppressed SREBP1 expression in BHT-101 but not FTC-133 cells. Olitigaltin, a galectin-3 inhibitor, decreased SREBP1 expression in a time- and dose-dependent manner in both cells. MK2206, an allosteric AKT inhibitor, did not change SREBP1 expression in either cell line. CONCLUSION: The galectin-3 inhibitor attenuates SREBP1 expression in thyroid cancer cells, likely independent of AKT phosphorylation. Lenvatinib and selumetinib decreases SREBP1 expression in the BRAF-mutant cell line BHT-101.
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Proteínas Proto-Oncogénicas B-raf , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Neoplasias de la Tiroides , Humanos , Proliferación Celular , Galectina 3 , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-akt , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismoRESUMEN
Accumulating evidence suggests that galectin-3 is a histologic marker of thyroid cancer. However, the pharmacological lectin-based approach has not been well studied. In the present study, we aimed to investigate the therapeutic potential of novel galectin-3 inhibitors by treating thyroid cancer cells with different concentrations of GB1107 or TD139. At high doses, TD139, but not GB1107, reduced cell viability and clonogenicity of thyroid cancer cells. TD139 induced apoptosis of thyroid cancer cells, as evident by an increase in the percentage of sub-G1 cells on cell cycle analysis, caspase-3 activation, and PARP1 cleavage. Either GB1107 or TD139 significantly inhibited cell coherence and counteracted anoikis resistance. Both inhibitors decreased migratory and invasive abilities in a dose-dependent manner. Furthermore, GB1107 and TD139 treatment attenuated AKT phosphorylation and decreased the expression of ß-catenin and MMP2. In conclusion, these novel galectin-3 inhibitors suppressed the anoikis resistance, motility, and invasive capacity of thyroid cancer cells at least partly through the AKT/ß-catenin pathway. Galectin-3 inhibitors are potentially suitable for preclinical evaluation of treatment and/or prevention of metastatic spread in thyroid cancer.
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INTRODUCTION: Lymphovascular invasion (LVI) is associated with disease recurrence and compromised survival in patients with thyroid cancer. Nonetheless, LVI is not identifiable on preoperative ultrasound or cytologic assessment. We aimed to explore the clinicopathological features associated with LVI. PATIENTS AND METHODS: We conducted a retrospective review of our prospectively maintained database from 2009 to 2018. Multivariate analyses were performed to determine the associations between clinicopathological parameters and LVI. Generalized additive models were used to examine the nonlinear relationship between continuous variables and LVI. RESULTS: A total of 795 patients were included in the analysis, and 174 (22%) had LVI. Patients' age (odds ratio [OR] = 0.982), tumor size (OR = 1.466), clinical lymphadenopathy (OR = 6.975), and advanced extrathyroidal extension (OR = 2.938) were independently associated with LVI. In the subset analysis of 198 patients with available genetic information, tumor size (OR = 1.599), clinical lymph node metastasis (OR = 3.657), and TERT promoter mutation (OR = 4.726) were predictive of LVI. Among 573 patients who had no clinical lymphadenopathy or advanced extrathyroidal extension, tumor size was the only predictor of LVI. Tumor size >1.5 cm had an increased risk of LVI based on the generalized additive model plot and receiver operating characteristic curve analysis. CONCLUSION: Tumor size is positively associated with the risk of LVI in papillary thyroid cancer. To avoid delayed treatment in patients with LVI, a tumor size of 1.5 cm may be considered as the safe upper limit for active surveillance.
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Vasos Sanguíneos/patología , Ganglios Linfáticos/patología , Linfadenopatía , Vasos Linfáticos/patología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adulto , Factores de Edad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Disección del Cuello , Invasividad Neoplásica , Regiones Promotoras Genéticas/genética , Estudios Retrospectivos , Factores de Riesgo , Telomerasa/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/terapia , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Tiroidectomía , Carga Tumoral , Espera VigilanteRESUMEN
We previously identified that the expression of chitinase-3-like protein 1 (CHI3L1) was upregulated during thyroid cancer progression. Here, we investigated the prognostic significance of CHI3L1 expression in thyroid neoplasms and examined the potential oncogenic roles. CHI3L1 immunochemical staining was performed on tissue microarrays of benign and malignant thyroid tumours. Compared with normal thyroid tissue and benign thyroid lesions that had low or no detectable CHI3L1 expression, CHI3L1 was overexpressed in both differentiated and undifferentiated thyroid cancer. High CHI3L1 expression was associated with extrathyroidal extension, lymph node metastasis, and shorter recurrence-free survival in differentiated thyroid cancer. The biological roles of CHI3L1 were further investigated by gain- and loss-of-function assays. CHI3L1 silencing suppressed clonogenicity, migration, invasion, anoikis resistance, and angiogenesis in thyroid cancer cells, although exogenous CHI3L1 treatment promoted these malignant phenotypes. Cysteine-rich angiogenic inducer 61 (CYR61) was identified as a downstream target of CHI3L1 by RNA-seq analysis. CYR61 silencing or treatment reversed the alterations induced by CHI3L1 modulation. Our results demonstrate that CHI3L1 is overexpressed in thyroid cancer and is associated with an increased risk of disease recurrence. Additionally, CYR61 may participate in CHI3L1-mediated tumour progression. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Biomarcadores de Tumor/metabolismo , Proteína 1 Similar a Quitinasa-3/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias de la Tiroides/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Neoplasias de la Tiroides/metabolismoRESUMEN
MTA2 is involved in tumor proliferation and metastasis. However, the role of MTA2 in cervical cancer thus far has not been identified. In this study, we report that elevated expression of MTA2 negatively correlates with Kallikrein-10 (KLK10) expression and poor prognosis of cervical cancer patients. Knockdown of MTA2 substantially inhibited tumor cell migration and invasion, and it enhanced KLK10 expression of the cervical cancer cells in vitro and in vivo. Functionally, shMTA2-mediated suppression of cell mobility was significantly restored by knockdown of KLK10. We also found that Sp1 (transcription factor specificity protein 1) is critical for shMTA2-induced transcriptional upregulation of KLK10 and subsequent biological functions. Furthermore, we found that the expression of miR-7 is elevated by MTA2 silencing and then by direct inhibition of Sp1 expression. Knockdown of Sp1 additively enhanced KLK10 expression in MTA2-knocked down cervical cancer cells, suggesting that the miR-7/Sp1 axis acts as an effector of MTA2 to impact KLK10 levels and mobility of cervical cancer cells. Taken together, our findings provide new insights into the physiological relationship between MTA2 and KLK10 via regulating the miR-7/Sp1 axis, and they provide a potential therapeutic target in cervical cancer.
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Alterations in the switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complex are enriched in advanced thyroid cancer. Integrase interactor 1 (INI1), encoded by the SMARCB1 gene on the long arm of chromosome 22, is one of the core subunits of the SWI/SNF complex. INI1 immunohistochemistry is frequently used for the diagnosis of malignant rhabdoid neoplasms. In the present study, we found normal and benign thyroid tissues generally had diffusely intense nuclear immunostaining. Loss of INI1 immunohistochemical expression was observed in 8% of papillary thyroid cancer and 30% of follicular thyroid cancer. Furthermore, loss of INI1 expression was associated with extrathyroidal extension (p < 0.001) and lymph node metastasis (p = 0.038). Analysis of The Cancer Genome Atlas database revealed that SMARCB1 underexpression was associated with the follicular variant subtype and aneuploidy in papillary thyroid cancer. We speculate that SMARCB1 is an important effector in addition to NF2 and CHEK2 inactivation among thyroid cancers with chromosome 22q loss.
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We aimed to ascertain whether therapeutic hypothermia (TH) acts as cardioprotective management for heat stroke (HS). Adult male rats under general anesthesia were exposed to whole-body heating (43°C for 70 min) to induce HS. Rats with HS displayed hyperthermia (core body temperature 42°C vs. 36°C); hypotension (30 mmHg vs. 90 mmHg mean arterial blood pressure); suppressed left ventricular (LV) performance (stroke volume 52 µl/min vs. 125 µl/min), ejection fraction (0.29% vs. 0.69%), relaxation factor (72 ms vs. 12 ms), and arterial elastance (0.31 mmHg/ µl vs. 10 mmHg/ µl); increased myocardial injury markers (e.g., creatine kinase-MB: 86 U/L vs. 24 U/L, cardiac troponin I: 3.08 ng/ml vs. 0.57 ng/ml); increased myocardial oxidative stress markers (e.g., malondialdehyde: 6.52 nmol/mg vs. 1.06 nmol/mg, thiobarbituric acid-reactive substances: 29 nmol/g vs. 2 nmol/g); decreased myocardial antioxidants (e.g., superoxide dismutase: 6 unit/mg vs. 17 unit/mg, reduced glutathione: 0.64 nmol/mg vs. 2.53 nmol/mg); increased myocardial proinflammatory cytokines (e.g., tumor necrosis factor-α 3200 pg/ml vs. 1000 pg/ml, interleukin-6: 668 pg/ml vs. 102 pg/ml); and increased cardiac damage scores (2.2 vs. 0.3). TH therapy significantly reversed the following conditions: HS-induced hyperthermia (37.5°C core body temperature), hypotension (71 mmHg), suppressed LV performance (stroke volume: 97 µl/min, ejection fraction: 0.65%, relaxation factor: 39 ms, and arterial elastance: 0.99 mmHg/µl), increased myocardial injury markers (e.g., creatine kinase-MB: 37 U/L, cardiac troponin I: 1.06 ng/ml), increased myocardial oxidative stress markers (e.g., malondialdehyde: 2.68 nmol/mg, thiobarbituric acid-reactive substances: 12.3 nmol/g), decreased myocardial antioxidants (e.g., superoxide dismutase: 13.3 unit/mg, reduced glutathione: 2.71 mmol/mg), increased myocardial proinflammatory cytokines (e.g., tumor necrosis factor-α 1500 pg/ml, interleukin-6: 108 ng/ml); and increased cardiac damage scores (0.9). We thus conclude that TH protects against HS-induced arterial hypotension by promoting LV performance in rats. These results add to the literature regarding the use of TH as cardioprotective management for HS.
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Arterias/fisiopatología , Golpe de Calor/terapia , Hipotensión/prevención & control , Hipotermia Inducida , Estrés Oxidativo , Función Ventricular , Anestesia General , Animales , Antioxidantes/metabolismo , Elasticidad , Lesiones Cardíacas/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hemodinámica , Calor , Inflamación , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Estimación de Kaplan-Meier , Masculino , Miocardio , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Hungry bone syndrome is characterized by prolonged and severe hypocalcemia following parathyroidectomy. Previously, we reported that preoperative alkaline phosphatase is a major factor predicting prolonged hospital stay. Nonetheless, some patients with low alkaline phosphatase levels presented with hungry bone syndrome, suggesting that additional factors may play a role. METHODS: From September 2010 to December 2017, consecutive dialysis patients who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Length of hospital stay was used as a surrogate marker for postoperative bone hunger. RESULTS: A total of 260 patients were included in the study. The median postoperative hospital stay was 3 days, and 69 (27%) patients had a stay longer than 3 days. Multivariate logistic regression analysis revealed that alkaline phosphatase (odds ratio [OR] = 1.005), osteocalcin (OR = 1.001), and subtotal parathyroidectomy (OR = 0.061) were associated with prolonged hospital stay. Multivariate linear regression analysis indicated that age (ß = - 0.170), alkaline phosphatase (ß = 0.430), and osteocalcin (ß = 0.166) were correlated with the length of stay. After surgery, the median osteocalcin level increased from 264 to 478 ng/mL (P < 0.001). CONCLUSIONS: Alkaline phosphatase is the main predictor of hungry bone syndrome after parathyroidectomy, and preoperative osteocalcin is an additional independent predictor. Patients with a high osteocalcin level may prone to have a higher demand for calcium supplementation.
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Hiperparatiroidismo Secundario/cirugía , Hipocalcemia/etiología , Osteocalcina/sangre , Paratiroidectomía/efectos adversos , Adulto , Fosfatasa Alcalina/sangre , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Tiempo de Internación , Masculino , Persona de Mediana Edad , Diálisis RenalRESUMEN
The pentose phosphate pathway (PPP) plays an important role in the biosynthesis of ribonucleotide precursor and NADPH. Cancer cells frequently increase the flux of glucose into the PPP to support the anabolic demands and regulate oxidative stress. Consistently, metabolomic analyses indicate an upregulation of the PPP in thyroid cancer. In the present study, we found that the combination of glucose-6-phosphate dehydrogenase (G6PD) and transketolase inhibitors (6-aminonicotinamide and oxythiamine) exerted an additive or synergistic effect on cell growth inhibition in thyroid cancer cells. Targeting PPP significantly increased cellular reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress and apoptosis. Suppressed cell viability could be partially rescued with treatment with the ROS scavenger or apoptosis inhibitor but not ER-stress inhibitor. Taken together, dual PPP blockade leads to pharmacologic additivity or synergism and causes ROS-mediated apoptosis in thyroid cancer cells.
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6-Aminonicotinamida/farmacología , Oxitiamina/farmacología , Vía de Pentosa Fosfato/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Tiroides/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucosafosfato Deshidrogenasa , Humanos , NADP/metabolismo , Estrés Oxidativo/efectos de los fármacos , Neoplasias de la Tiroides/tratamiento farmacológicoRESUMEN
Over the last two decades, there have been no significant changes in patient outcomes in relation to the treatment of osteosarcoma, an aggressive malignant neoplasm. It is known that vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and in osteosarcoma. Moreover, VEGF-A expression correlates with clinical stages of osteosarcoma. The adipokine resistin exhibits proinflammatory, proangiogenic and metastatic properties, and evidence suggests that resistin may serve as a prognostic biomarker linking obesity and inflammation to cancer. However, whether resistin has a role in osteosarcoma angiogenesis is unclear. This investigation shows that resistin promotes VEGF-A expression in human osteosarcoma cells and activates the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 signaling pathways, while ERK, JNK, and p38 inhibitors or their small interfering RNAs (siRNAs) inhibit resistin-induced VEGF-A expression as well as endothelial progenitor cell (EPC) migration and tube formation. We also found that resistin upregulates VEGF-A expression by enhancing activation of the transcription factor nuclear factor-kappa B (NF-κB). Finally, resistin promotes angiogenesis in the chick chorioallantoic membrane (CAM) model. Resistin appears to be a promising target for human osteosarcoma.
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Sistema de Señalización de MAP Quinasas , Neovascularización Patológica , Osteosarcoma/metabolismo , Resistina/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Línea Celular Tumoral , Embrión de Pollo , Evaluación Preclínica de Medicamentos , Humanos , FN-kappa B/metabolismoRESUMEN
BACKGROUND/AIM: Parathyroidectomy has beneficial effects on all-cause and cardiovascular mortality in patients with uncontrolled hyperparathyroidism. B-Type natriuretic peptide (BNP) correlates with the severity of heart failure. We aimed to investigate whether parathyroidectomy modulates the BNP levels in dialysis patients. PATIENTS AND METHODS: Patients who underwent surgical intervention for hyperparathyroidism were included. The serum BNP levels were determined before parathyroidectomy and during follow-up. RESULTS: The preoperative and postoperative BNP levels were 499±561 and 453±442 pg/ml, respectively (p=0.82). The baseline BNP level was positively correlated with weakness and headache, but not biochemical parameters. In multivariate analysis, age (odds ratio=0.837) and preoperative symptom score (odds ratio=0.935) were independent predictors for the postoperative decline in BNP levels Conclusion: The serum BNP levels may increase or decrease after parathyroidectomy. Younger age and lower symptom burden are associated with decline in BNP levels.
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Biomarcadores , Péptido Natriurético Encefálico/sangre , Paratiroidectomía , Diálisis Renal , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hiperparatiroidismo/sangre , Hiperparatiroidismo/cirugía , Masculino , Persona de Mediana Edad , Paratiroidectomía/efectos adversosRESUMEN
BACKGROUND: Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. METHODS: We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity-score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. RESULTS: After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF-like vs RAS-like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix-associated pathways were enriched in the MSigDB database. CONCLUSION: Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.