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1.
Front Psychiatry ; 12: 782289, 2021.
Article in English | MEDLINE | ID: mdl-34955927

ABSTRACT

Background: A growing body of evidence shows that immune system disorders are one of the important etiological factors of schizophrenia. Inflammatory cytokines play a very critical role in the pathogenesis and treatment of schizophrenia. However, in the actual clinical practice, there is still a lack of confirmed biological indicators that can be used to evaluate the therapeutic effect of antipsychotics. Methods: In this study, 82 male patients with first-episode schizophrenia and 30 healthy controls were included. The Positive and Negative Syndrome Scale (PANSS) scores were evaluated, and the serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 17 (IL-17), and transforming growth factor ß1 (TGF-ß1) were detected, both at baseline and 4 weeks later. The patients were divided into two groups, the effective group and the ineffective group, according to the reduction rate of PANSS. Results: In the case group, the levels of hs-CRP were significantly elevated (p = 0.00), whereas IL-1ß, IL-6, and IL-17 were significantly reduced as compared to the baseline (p = 0.01, 0.02, and 0.00, respectively). Importantly, the baseline levels of the five inflammatory factors were significantly higher in the case group as compared to the control group (p = 0.00, 0.00, 0.00, 0.00, and 0.00, respectively). Post-treatment, the serum levels for IL-1ß, IL-6, and IL-17 were significantly higher in the effective group than in the ineffective group (p = 0.00, 0.00, and 0.01, respectively). For every increase in the amount of IL-1ß, the risk of ineffectiveness increased by 7% (OR = 0.93 [0.86-1.00]; p = 0.04), whereas for every increase in the amount of IL-17, the risk of ineffectiveness increased by 5% (OR = 0.95 [0.90-0.99]; p = 0.03). Conclusion: The results of the study showed that the levels of inflammatory factors in patients with different therapeutic effects were different, and the changes in the amounts of IL-1ß and IL-17 acted as predictors of poor efficacy.

2.
J Pathol ; 253(1): 106-118, 2021 01.
Article in English | MEDLINE | ID: mdl-33009820

ABSTRACT

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.


Subject(s)
Adenocarcinoma/enzymology , Biomarkers, Tumor/metabolism , Carcinoma, Neuroendocrine/enzymology , Epigenesis, Genetic , Hepatocyte Nuclear Factor 3-beta/metabolism , Histone Demethylases/metabolism , Prostatic Neoplasms/enzymology , Transcription Factors/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Animals , Biomarkers, Tumor/genetics , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/secondary , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 3-beta/genetics , Histone Demethylases/genetics , Humans , Male , Mice, Inbred C57BL , Mice, Knockout , Mice, Nude , PC-3 Cells , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Transcription Factors/genetics , Transcription, Genetic , Up-Regulation
3.
Front Oncol ; 10: 1234, 2020.
Article in English | MEDLINE | ID: mdl-32850370

ABSTRACT

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with ß-catenin to transcriptionally upregulate LEF1 and subsequently enhances EMT-mediated cancer progression. More importantly, LSD1 specific inhibitor GSK2879552 is capable of repressing tumor progression in patient-derived tumor xenograft. These findings altogether suggest that LSD1 can serve as not only a prognostic biomarker but also a promising therapeutic target in bladder cancer treatment.

4.
J Geriatr Psychiatry Neurol ; 32(6): 312-318, 2019 11.
Article in English | MEDLINE | ID: mdl-31480989

ABSTRACT

OBJECTIVE: To estimate the prevalence of depressive symptoms (depression thereafter) and to identify the sociodemographic and clinical correlates of depression in a sample of elderly patients treated in the primary care setting in Wuhan, China. BACKGROUND: Primary care is an opportune setting for the management of late-life depression in China, but there have been no representative studies on the clinical epidemiology of depression in elderly Chinese primary care patients. METHODS: In total, 752 elderly patients (≥ 65 years) were consecutively recruited from 13 primary care centers in Wuhan, China, and interviewed with a standardized questionnaire. Depression was assessed with the 15-item Geriatric Depression Scale (GDS-15). RESULTS: Of the elderly Chinese primary care patients, 30.6% had depression (GDS-15 ≥ 5). Correlates of depression were an education level of primary school or less (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.36-2.77, P < .001), poor financial status (OR: 2.19, 95% CI: 1.16-4.15, P = .016), lack of an exercise habit (OR: 1.40, 95% CI: 1.06-1.74, P = .023), 2 or more chronic medical conditions (OR: 1.90, 95% CI: 1.34-2.69, P < .001), and loneliness (OR: 3.53, 95% CI: 2.46-5.08, P < .001). CONCLUSIONS: Depression is prevalent among elderly Chinese primary care patients, indicating that elderly patients treated in primary care have a high level of need for mental health services in China. There is an urgent need to integrate mental health services into primary health care.


Subject(s)
Depression/diagnosis , Primary Health Care/standards , Aged , China/epidemiology , Depression/epidemiology , Female , Humans , Male , Prevalence
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