Long non-coding RNA ANRIL mitigates neonatal hypoxic-ischemic brain damage via targeting the miR-378b/ATG3 axis.

Hypoxic-ischemic brain injury (HIBD) is the most common form of brain injury in newborns and is a major burden on society. However, the molecular mechanism of HIBD remains unclear. Long non-coding RNA (lncRNA) has been demonstrated to be a key regulator in brain development and numerous neurological diseases. The present study identified the role and underlying mechanism of lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) in HIBD. The data indicated that ANRIL expression was significantly increased in hypoxia-stressed primary neurons and PC12 cells. Silencing ANRIL aggravated oxygen-glucose deprivation-induced cell injury. Mechanistically, microRNA (miR)-378b was predicted and confirmed as a direct target of ANRIL. A miR-378b inhibitor counteracted the effect of ANRIL on hypoxia-induced cell injury. Furthermore, ANRIL positively regulated autophagy related 3 (ATG3) expression and promoted autophagy through competitively binding to miR-378b. Overall, the present findings suggest that ANRIL exerts its protective effects via binding to miR-378b and upregulating ATG3 expression, suggesting the potential of ANRIL as a protective target for HIBD.

Genistein alleviates atherosclerosis in apolipoprotein E-deficient mice by interrupting the OX40/OX40L pathway.

More and more evidence shows that the OX40/OX40L interaction plays a critical role in the development of atherosclerosis. However, it is not known whether genistein, a natural phytoestrogen with anti-inflammatory effects found in soybean extract, can prevent experimental atherosclerosis by regulating the OX40/OX40L pathway. This study aims to explore the effect and the underlying mechanisms of genistein on the development of atherosclerosis in apolipoprotein E gene knockout (ApoE-/-) mice. ApoE-/- mice, fed an atherogenic diet, were treated with genistein (15 and 45 mg kg-1 day-1). In vitro studies were carried out in oxidized LDL (oxLDL)-stimulated SMCs. Our results show that genistein treatment remarkably reduced atherosclerotic plaque formation and reduced the serum levels of pro-inflammatory cytokines in ApoE-/- mice. Also, genistein promotes plaque stability in ApoE-/- mice, characterized by smaller necrotic core areas of atherosclerotic plaques and reduced MMP-9 protein expression in primary smooth muscle cells (SMCs). Furthermore, when mRNA expression and the protein expression of OX40 were significantly increased, they were inhibited by genistein in response to an atherogenic diet. Notably, ApoE-/- mice with an anti-OX40L antibody presented a significant decrease in atherosclerotic lesion formation, which has no further beneficial effects when combined with genistein. These results suggest that genistein potentially has atheroprotective effects that involve the inhibition of the OX40/OX40L pathway, which could be used to prevent and treat atherosclerosis.

Idiopathic granulomatous mastitis: a 10-year study from a multicentre clinical database.

Idiopathic granulomatous mastitis (IGM) is an uncommon, chronic inflammatory breast disease with elusive aetiology, simulating malignancy clinically and radiologically. Here we present our 10-year review on a region-wide multicentre IGM database. A retrospective study was performed on a prospectively maintained database from three University affiliated hospitals in Hong Kong and Shenzhen, China. All patients with biopsy proven IGM were included while patients with positive culture of Mycobacterium tuberculosis were excluded. Disease recurrence rate and its prognosticators were evaluated. A total of 102 patients were included between January 2007 and December 2017. Median age was 33 years (range 20-54). Most patients presented with painful inflammatory mass (n = 57); median size at presentation was 37 mm (6-92 mm). Sixty-three patients had bacterial culture performed on the pus sample: eight patients had Corynebacterium kroppenstedtii while four had Corynebacterium species not otherwise specified. Seventy-seven (75.5%) patients received conservative treatment with oral corticosteroid (±antibiotics) and drainage only, while 25 (24.5%) patients received breast lump excision after initial medical treatment. Twelve (11.8%) patients developed recurrence after a median follow-up interval of 14 months (4-51 months). Univariate analysis revealed that abscess on presentation, history of smoking, and presence of C. kroppenstedtii were significant prognosticators for recurrence. Subsequent multivariate analysis with logistic regression revealed cigarette smoking and isolation of C. kroppenstedtii as independent risk factors for disease recurrence (p < 0.05). In conclusion, IGM is uncommon with a recurrence rate of 12%, especially in patients with history of smoking and isolation of C. kroppenstedtii.

Coexistence of Ductal Carcinoma Within Mammary Phyllodes Tumor: A Review of 557 Cases From a 20-year Region-wide Database in Hong Kong and Southern China.

INTRODUCTION: Phyllodes tumor (PT) is an uncommon fibroepithelial tumor of the breast showing predominately proliferation of the stromal component. The presence of ductal carcinoma in situ (DCIS) or invasive ductal carcinoma is rare, with only a few cases reported in the literature. METHODS: A retrospective review of a prospectively maintained database was performed. Patients who were treated for PT in 5 hospitals in Hong Kong and Shenzhen, China over a period of 20 years (1997-2016) were evaluated. All pathology slides were reported by specialist pathologists. Patients with coexisting ductal carcinoma were identified. RESULTS: A total of 557 patients were included in this cohort; 363 (65.2%) patients had benign PT, 130 (23.3%) had borderline PT, and 64 (11.5%) had malignant PT. There were 6 (1.1%) patients with coexisting ductal carcinoma in the PT; 5 were DCIS and 1 was invasive ductal carcinoma. The median age was 46.5 years (range, 25-54 years). Ductal carcinoma occurred more frequently in malignant PT than in benign or borderline PT (4.7% vs. 0.6%; P = .02). However, malignant PT was not associated with higher DCIS grade (P = .1). All patients underwent surgery with clear resection margins. After a median follow-up interval of 70 months (range, 2-101 months), all patients remained disease- and recurrence-free. CONCLUSION: We report 6 additional uncommon cases of ductal carcinoma complicating PT. The presence of ductal carcinoma was not adverse prognosticator as these are usually incidental and situated within the harboring PT.

Thymosin alpha-1-transformed Bifidobacterium promotes T cell proliferation and maturation in mice by oral administration.

Thymosin alpha-1 (Tα1) has been used as an immune potentiator for treatment of immune deficiency diseases by injection administration. However, injection is inconvenient and may cause many side effects. In order to improve the administration convenience of Tα1, a human Tα1 gene transformed Bifidobacterium longum (BL-Tα1) was prepared and its effects on mice immunity by oral administration were investigated. The Balb/c mice were treated with BL-Tα1, which was pre-induced with 0.2% l-arabinose, every other day for 2 weeks. The B. longum transformed with empty vector (BL-0) was used as the negative control, and normal saline (NS, 0.9% saline) was used as the blank control. The results shown that (1) the CD3(+)CD4(+) and CD3(+)CD8(+) T-cells in blood, spleen and thymus, and the CD4(+)CD8(+) cells in thymus and spleen of BL-Tα1 group were all significantly increased than that of negative control BL-0 group respectively; (2) the interferon-γ (IFN-γ) and interleukin-12 (IL-12) in serum of BL-Tα1 group were significantly increased. No significant differences were found in the levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) between BL-Tα1 group and BL-0 group; (3) thymic hyperplasia and lymphadenectasis were observed in BL-Tα1 group after three-month treatment. In conclusion, the Tα1-transformed B. longum promotes thymus and lymph nodes growth, stimulates T cell proliferation and maturation, and enhances cellular immunity through Th1 pathway by oral administration.