Prevalence of self-reported thyroid disease among adults with depression.

BACKGROUND: Thyroid disorders are a common comorbidity in patients with depression, yet there is limited information available about the clinical epidemiology of thyroid diseases in this specific population. This study aims to describe the prevalence of thyroid disease among US adults with depression from 2007 to 2018. METHODS: This cross-sectional study used nationally representative data collected through the National Health and Nutrition Examination Survey (NHANES) between January 1, 2007, to December 31, 2018. Age-standardized prevalence of thyroid disease among depressed patients was calculated within 4-year survey periods (2007-2010, 2011-2014, and 2015-2018), and adjusted to the 2000 U.S. standard population. RESULTS: In our weighed sample, 6.1% of depressed individuals and 4.3% of non-depressed individuals reported thyroid disease between 2007 and 2018 (P < 0.0001). The age-standardized prevalence of thyroid disease in patients with depression increased over time, from 5.4% (95%CI, 4.6%-6.2%) in 2007-2010 to 6.8% (95%CI, 5.8%-8.0%) in 2015-2018 (P for trend = 0.0270). Furthermore, thyroid disease prevalence was highest in non-Hispanic white individuals, increased with age, and tended to be higher in women. Mean depression scores in patients with thyroid disease (9.1; 95%CI, 8.7-9.5) did not significantly different from those without thyroid disease (9.1; 95%CI, 9.0-9.3) (P = 0.96). CONCLUSION: The age-standardized prevalence of thyroid disease among US adults with depression exhibited a consistent increase from 2007 to 2018, with the highest rate occurring in older, non-Hispanic white individuals, and women.

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis.

BACKGROUND: Previous studies have suggested that systemic metabolic abnormalities are closely related to psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear. METHODS: In this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL. RESULTS: Compared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves. CONCLUSION: GGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

Prevalence and Trends of Thyroid Disease Among Adults, 1999-2018.

BACKGROUND: Thyroid disease is a prominent endocrine disorder, yet the clinical epidemiology of this condition remains unclear. This study aims to describe the recent trends in the prevalence of thyroid disease in US adults from 1999-2018. METHODS: This cross-sectional study used nationally representative data collected through the National Health and Nutrition Examination Survey (NHANES) from January 1, 1999 to December 31, 2018. Patients with thyroid disease were defined as patients who reported having a thyroid disease and were on thyroid-related treatment. Age-standardized prevalence of thyroid disease was calculated within 4-year survey periods (1999-2002, 2003-2006, 2007-2010, 2011-2014, and 2015-2018). RESULTS: During the NHANES 1999-2018, a total of 57 540 participants were examined. The age-standardized prevalence of thyroid disease was 5.05% (95% CI, 4.55%-5.60%) from 2015-2018, signifying a significant increase from the 1999-2002 period (P <.0002). However, prevalent thyroid disease remained steady between 2003 and 2014. The highest prevalence of thyroid disease was observed in non-Hispanic Whites (8.1%; 95% CI, 7.3%-9.0%), individuals aged ≥60 years (15.4%; 95% CI, 13.3%-17.8%), and tended to be higher in women (7.6%; 95% CI, 6.8%-8.5%). Multiple regression analysis revealed that age, women sex, non-Hispanic White and Mexican American, body mass index, higher education and incomes were independently associated with increased risks of thyroid disease. CONCLUSION: The age-standardized prevalence of thyroid disease among US adults increased from 1999-2003, remained stable between 2003 and 2014, and then saw an increase from 2014-2018, with the highest rate observed among elders, women, and non-Hispanic Whites.

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Abstract Background Previous studies have suggested that systemic metabolic abnormalities are closely related to psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear. Methods In this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL. Results Compared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves. Conclusion GGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

Corrigendum: Dihydrocapsaicin inhibits cell proliferation and metastasis in melanoma via down-regulating ß-catenin pathway.

[This corrects the article DOI: 10.3389/fonc.2021.648052.].

Dihydrocapsaicin Inhibits Cell Proliferation and Metastasis in Melanoma via Down-regulating ß-Catenin Pathway.

Dihydrocapsaicin (DHC) is one of the main components of capsaicinoids in Capsicum. It has been reported that DHC exerts anti-cancer effects on diverse malignant tumors, such as colorectal cancer, breast cancer, and glioma. However, studies focused on the effect of DHC upon melanoma have rarely been done. In the present study, melanoma A375 and MV3 cell lines were treated with DHC and the cell proliferation, migration, and invasion were significantly suppressed. Furthermore, DHC effectively inhibited xenograft tumor growth and pulmonary metastasis of melanoma cells in NOD/SCID mice model. It was identified that ß-catenin, which plays significant roles in cell proliferation and epithelial-mesenchymal transition, was down-regulated after DHC treatment. In addition, cyclin D1, c-Myc, MMP2, and MMP7, which are critical in diverse cellular process regulation as downstream proteins of ß-catenin, were all decreased. Mechanistically, DHC accelerates ubiquitination of ß-catenin and up-regulates the beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) in melanoma cells. The DHC induced suppression of cell proliferation, migration, and invasion were partly rescued by exogenous ß-catenin overexpression, both in vitro and in vivo. Taken together, DHC may serve as a candidate natural compound for human melanoma treatment through ß-catenin pathway.

CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9.

As a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression, but its biological functions and molecular mechanisms in melanoma remain unknown. Our study showed that CSN6 expression was upregulated in melanoma patients and cells, and correlated with poor survival in melanoma patients. In melanoma cells, CSN6 knockdown remarkably inhibited cell proliferation, tumorigenicity, migration, and invasion, whereas CSN6 recovery rescued the proliferative and metastatic abilities. Notably, we identified that CSN6 stabilized CDK9 expression by reducing CDK9 ubiquitination levels, thereby activating CDK9-mediated signaling pathways. In addition, our study described a novel CSN6-interacting E3 ligase UBR5, which was negatively regulated by CSN6 and could regulate the ubiquitination and degradation of CDK9 in melanoma cells. Furthermore, in CSN6-knockdown melanoma cells, UBR5 knockdown abrogated the effects caused by CSN6 silencing, suggesting that CSN6 activates the UBR5/CDK9 pathway to promote melanoma cell proliferation and metastasis. Thus, this study illustrates the mechanism by which the CSN6-UBR5-CDK9 axis promotes melanoma development, and demonstrate that CSN6 may be a potential biomarker and anticancer target in melanoma.

ZC3H15 Correlates with a Poor Prognosis and Tumor Progression in Melanoma.

Zinc figure CCCH-type containing 15 (ZC3H15), also called developmentally regulated GTP-binding protein 1 (DRG1) family regulatory protein 1 (DFRP1), is a zinc finger containing protein. Despite playing a role in cellular signaling, it is found overexpressed in acute myeloid leukemia and also an independent prognostic marker in hepatocellular carcinoma patients. However, the biological effect of ZC3H15 in malignant melanoma (MM) remains unexplored. The expression of ZC3H15 in patients was analyzed using the R2: Genomics Analysis and Visualization Platform database. Immunohistochemical analysis, western blot, and qRT-PCR were used to detect ZC3H15 expression in melanoma tissues and cell lines. MTT, BrdU, flow cytometry assay, transwell, and western blot were performed to explore the proliferation, cell cycle, invasion, and migration of melanoma cells. We undertaken colony formation assay in vitro and tumor xenograft in vivo to detect the tumorigenicity of melanoma cells. In the present study, ZC3H15 was demonstrated highly expressed in melanoma tissues and cells. Elevated ZC3H15 impairs the survival of melanoma patients. Meanwhile, attenuation of ZC3H15 in melanoma cells inhibited cell proliferation and induced cycle arrest at G0/G1 phase. Consistently, the expression of cell cycle-related proteins cyclin dependent kinase 4 (CDK4), CDK6, and cyclin D1 (CCND1) was decreased while p21 was upregulated. Furthermore, we found the migration and invasion abilities were inhibited in ZC3H15-knockdown melanoma cells. In addition, downregulation of ZC3H15 resulted in inhibition of colony formation abilities in vitro and tumorigenesis in vivo. ZC3H15 promotes proliferation, migration/invasion, and tumorigenicity of melanoma cells. As a promising biomarker and therapeutic target in MM, ZC3H15 is worthy of further exploration.

Dehydrocorydaline inhibits cell proliferation, migration and invasion via suppressing MEK1/2-ERK1/2 cascade in melanoma.

Purpose: Alkaloids are naturally occurring chemical compounds that are widely distributed in plants, and have pharmaceutical values and low toxicity. In recent years, some of them have been demonstrated to be promising therapeutic drug candidates for cancer treatment. Herein, we tried to explore the antitumor effect of dehydrocorydaline (DHC), a natural alkaloid isolated from Corydalis, on malignant melanoma. Methods: We treated two malignant metastatic melanoma cell lines, A375 and MV3, and a normal melanocyte cell line, PIG1, with various concentrations of DHC for set amounts of time, and detected cell proliferation, migration, and invasion by using MTT, BrdU, transwell, Western blot and soft agar assay in vitro and tumorigenicity in the xenografts in vivo. Results: Our results showed that DHC dramatically blocked cell proliferation and led to cell cycle arrest at G0/G1 phase and downregulated the expressions of cell cycle regulators CDK6 and Cyclin D1 in melanoma cells. However, DHC had little inhibitory effect on normal melanocyte cell line PIG-1. Meanwhile, DHC suppressed cell invasion and migration through modulating the epithelial-mesenchymal transition (EMT) markers including E-cadherin, vimentin, as well as ß-catenin. In addition, DHC also significantly attenuated tumor growth in vivo. The expressions of cell cycle-related and metastasis-related proteins were further confirmed by immunohistochemical staining in the xenografts. Importantly, MEK1/2-ERK1/2 cascade was inactivated after DHC treatment and ERK activator t-butylhydroquinone (tBHQ) treatment rescued DHC-induced cell proliferation inhibition. Conclusions: Our results indicated that DHC inhibited cell proliferation and migration/invasion via inactivating MAPK signaling, and showed that DHC might be a potential novel drug to treat malignant melanoma.

Fatal Vitamin K-Dependent Coagulopathy Associated with Cefoperazone/Sulbactam: A Case Report.

This case report describes a suspected and fatal adverse reaction involving vitamin K-dependent coagulopathy that might be associated with cefoperazone/sulbactam (CPZ/SAM), a combined antimicrobial formulation. We reported a patient diagnosed with acute cerebral infarction and secondary pulmonary infection who was treated with an intravenous infusion of CPZ/SAM at 3 g twice daily. After receiving treatment with CPZ/SAM, the patient developed a fatal adverse reaction of CPZ-induced hemorrhage. The Naranjo assessment score in this report was 5, suggesting that the patient's coagulation function disorder was potentially associated with the use of CPZ/SAM. To prevent vitamin K-dependent coagulopathy caused by CPZ/SAM, it is suggested to avoid cephalosporins in patients with a high risk of bleeding unless the need for cephalosporins is compelling.

Inactivation/deficiency of DHODH induces cell cycle arrest and programed cell death in melanoma.

Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells. Then we found that BCL-2 could rescue apoptosis induced by DHODH inactivation/deficiency. Moreover, BCL-2 also showed to promote cell cycle arrest and to inhibit autophagy induced by leflunomide. To explore the mechanisms underlying autophagy induced by DHODH inhibition, we found that AMPK-Ulk1 axis was activated in this process. Besides, JNK was phosphorylated and activated to phosphorylate BCL-2, which abrogated the interaction between BCL-2 and Beclin1 and then abolished autophagy. Our findings provided evidences for the potential of DHODH used as a drug target for melanoma treatment.

Antibiotic drug tigecycline inhibits melanoma progression and metastasis in a p21CIP1/Waf1-dependent manner.

Antibiotics are common drugs with low toxicity but high effectiveness. They have been suggested to be drug candidates for cancer therapy in recent years. Here, we tried to investigate the antitumour effect of tigecycline on malignant melanoma. We showed that tigecycline dramatically inhibited cell proliferation and induced cell cycle arrest at G0/G1 phase. At the same time, tigecycline suppressed cell invasion and migration through preventing epithelial-mesenchymal transition (EMT) process. In addition, tigecycline also significantly blocked tumor growth in vivo. Expression of cell cycle-related proteins were investigated and resulted in downregulation of G1/S checkpoint proteins, such as CDK2 and Cyclin E. However, cyclin-dependent kinase inhibitor 1 (CDKN1A, p21(CIP1/Waf1)) was downregulated after tigecycline treatment, which was not conformed to its conventional function. To explain this, we overexpressed p21 in melanoma cells. We found that p21 overexpression significantly rescued tigecycline-induced cell proliferation inhibition as well as migration and invasion suppression. Taken together, our results revealed that the essential role of p21 in the inhibitory effect of tigecycline on proliferation, migration and invasion of melanoma. Tigecycline might act as a candidate therapeutic drug for treatment of patients suffering from malignant melanoma.

Function and mechanism of neurotensin (NTS) and its receptor 1 (NTSR1) in occurrence and development of tumors.

As a neuropeptide, neurotensin (NTS) is widely expressed in central and peripheral nervous system, which is mainly mediated byneurotensin receptor1 (NTSR1) to activate the related downstream signaling pathways. After summarized the function and mechanism of NTS/NTSR1 in various malignant tumors, we found that NTS/NTSR1 played essential roles during tumor initiation and development. NTS/NTSR1 regulates tumor initiation, proliferation, apoptosis, metastasis and differentiation mainly through three pathways, including IP3/Ca2+ /PKC/MAPKs pathway, MMPs/EGFR/MAPKs (PI3K/Akt) pathway, or Rho-GTPsaes and non-receptor tyrosine kinase pathway. Besides, NTS/NTSR1 is also regulated by some upstream pathways and some traditional Chinese medicine preparations and traditional Chinese medicine therapies. In this article, we summarized the function of NTS/NTSR1 and its mechanisms, and discussed the prospective in its application to clinical diagnosis and drugs targeting.