Brain-derived neurotrophic factor (BDNF), a critical modulator in the neurodevelopment and maintenance of both central and peripheral nervous systems, is regarded as a potential therapeutic target of Parkinson's disease (PD). However, its association with PD remains unclear and the data are inconsistent. To explore the correlation, studies reporting BDNF levels in PD patients and healthy controls are searched and a sample of 1496 participants are pooled in the meta-analysis, demonstrating significantly decreased serum levels of BDNF in PD patients when compared with the healthy controls (SMD = -1.03; 95% CI [-1.83, -0.23]; P = .012). Meta-regression analysis indicates gender is an important confounding factor (Adj R2 = 69.20%, p = .004, I2 res = 90.64%), whereas age (Adj R2 = 11.91%, P = .95, I2 res = 96.86%), H-Y stages of PD progression (Adj R2 = -30.18%, P = .612, I2 res = 96.62%) and MoCA score assessed cognitive impairment (Adj R2 = 2.18%, P = .517, I2 res = 64.41%) show few moderating effects. The research provides evidence of moderate quality that blood levels of BDNF are decreased in PD patients despite various influencing factors, supporting an association between decreased level of peripheral BDNF and PD.

Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast cancer by inhibiting CHEK2’s activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast cancer, which protects cells from apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast cancer.

Background. Peutz‐Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by a germline mutation in the STK11 gene. It is characterized by mucocutaneous pigmentation, gastrointestinal hamartomatous polyps, and cancer predisposition. Aims. We aimed to summarize the main clinical and genetic features of Chinese PJS patients and assessed the genotype‐phenotype correlations. Methods. Thirty‐eight patients clinically diagnosed with Peutz‐Jeghers syndrome were included in this study from 2016 to 2019. Combined direct sequencing and multiplex ligation‐dependent probe amplification tests were used to detect germline heterogeneous STK11 mutations. RNA sequencing was performed in polyps of PJS patients and control groups to evaluate the difference in expression of STK11. The genotype‐phenotype correlations were calculated by Kaplan‐Meier analyses. Results. All 26 probands and 12 affected relatives had germline heterogeneous STK11 mutations among which 8 variants were novel. Individuals with missense mutations had their first surgery and other symptoms significantly later than individuals with null mutations. Conclusion. This study expanded the spectrum of STK11 gene mutations and further elucidated individuals with null mutations of STK11 typically had an earlier onset of PJS symptoms and needed earlier management.

Breast cancer, one of the most prevalent neoplasms in the world, continues attracting worldwide attention. Macrophage, as the most abundant non-malignant cell in tumor, plays critical roles in both immune surveillance and tumorigenesis and has become a cell target of immunotherapy. Among all macrophages, tumor-associated macrophage (TAM) is regarded as the main force to promote tumorigenesis. To get an overall view of its impact on breast cancer, we employed a simplified and indirect coculturing cell model followed by RNA-sequencing to detect cancer cell’s transcriptomic response induced by TAM and a prognostic gene signature was constructed based on it. Evidence from both cell models and clinical samples strengthened TAM’s full-dimensional impact on breast cancer, involved in almost all known signal pathways dysregulated during tumorigenesis from transcription, translation and molecule transport to immune-related pathways. Consequently, the gene signature developed from these genes was tested to be powerful in prognostic prediction and associated with various clinical and biological features of breast cancer. Our study presented a more complete view of TAM’s impact on breast cancer, which strengthened its role as an important therapy target. A 45-gene signature from the TAM-regulated genes was developed and shown potential in clinical application.

The nuclear envelope component proline-rich protein 14 (PRR14) is involved in the nuclear morphological alteration and activation of the mTOR (mammalian target of rapamycin) signaling pathway, and has been repeatedly shown to be upregulated in patients with Parkinson’s disease (PD). The aim of this study was to explore whether PRR14 can be used as a potential biomarker for the diagnosis of PD. We compared PRR14 expression in PD patients and normal controls in gene expression omnibus (GEO) data. Quantitative enzyme-linked immunosorbent assay (ELISA) was used to detect PRR14 expression in PD patients and age- and sex-matched controls. The relationship between serum PRR14 and clinical phenotype was evaluated using correlation analysis and logistic regression. The expression of PRR14 in whole blood, substantia nigra, and medial substantia nigra was significantly higher in PD patients than in the healthy control group. Compared to plasma, serum was more suitable for the detection of PRR14. Furthermore, serum PRR14 level in PD patients was significantly higher than that in age- and sex-matched controls. The area under the curve for serum PRR14 level in the ability to identify PD versus age- and sex-matched controls was 0.786. In addition, serum PRR14 level was found to correlate with constipation in PD patients. Our findings demonstrate for the first time that serum PRR14 is a potential biomarker for PD.

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