Institutional shareholders and corporate governance

Our paper focus on institutional investors and the role that they play in corporate governance. An empirical analysis is done on institutions' shareholdings in all mainboard companies listed on the Singapore Exchange

Up-Regulated Expression of Pro-Apoptotic Long Noncoding RNA lincRNA-p21 with Enhanced Cell Apoptosis in Lupus Nephritis

Accelerated cell apoptosis with dysregulated long noncoding RNAs is the crucial pathogenesis in lupus nephritis (LN). Pro-apoptotic lincRNA-p21 was studied in LN patients, cell lines with lentivirus-mediated overexpression and CRISPR interference (CRISPRi)-conducted repression, and a mouse model. Clinical samples were from patients and age/sex-matched controls. Expression of lincRNA-p21 and endogenous RNA target miR-181a, were examined in mononuclear and urine cells. Guide RNA sequences targeting lincRNA-p21 were cloned into CRISPRi with dCas9/ Krüppel-associated box (KRAB) domain. LincRNA-p21-silened transfectants were investigated for apoptosis and miR-181a expression. LincRNA-p21-overexpressed cells were evaluated for apoptosis and p53-related down-stream molecules. Balb/C mice were injected with pristane to induce LN and examined for apoptosis and lincRNA-p21. Higher lincRNA-p21 levels were found in LN mononuclear and urine cells, positively correlated with activity. There were lower miR-181a levels in LN mononuclear cells, negatively correlated with activity. Doxorubicin-induced apoptotic cells had up-regulated lincRNA-p21 levels. CRISPRi with dCas9/KARA domain showed efficient repression ability on transcription initiation/elongation. CRISPRi-conducted lincRNA-p21-silenced transfectants displayed reduced apoptosis with up-regulated miR-181a levels, whereas lentivirus-mediated lincRNA-p21-overexpressed cells revealed enhanced apoptosis with up-regulated downstream PUMA/Bax expression. LN mice had glomerular apoptosis with progressive increased lincRNA-p21 levels. Our results demonstrate up-regulated lincRNA-p21 expression in LN, implicating a potential diagnostic marker and therapeutic target

Targeting Intra-Pulmonary P53-Dependent Long Non-Coding RNA Expression as a Therapeutic Intervention for Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage

Diffuse alveolar hemorrhage (DAH) in systemic lupus erythematosus (SLE) is associated with significant mortality, requiring a thorough understanding of its complex mechanisms to develop novel therapeutics for disease control. Activated p53-dependent apoptosis with dysregulated long non-coding RNA (lncRNA) expression is involved in the SLE pathogenesis and correlated with clinical activity. We examined the expression of apoptosis-related p53-dependent lncRNA, including H19, HOTAIR and lincRNA-p21 in SLE-associated DAH patients. Increased lincRNA-p21 levels were detected in circulating mononuclear cells, mainly in CD4+ and CD14+ cells. Higher expression of p53, lincRNA-p21 and cell apoptosis was identified in lung tissues. Lentivirus-based short hairpin RNA (shRNA)-transduced stable transfectants were created for examining the targeting efficacy in lncRNA. Under pristane stimulation, alveolar epithelial cells had increased p53, lincRNA-p21 and downstream Bax levels with elevated apoptotic ratios. After pristane injection, C57/BL6 mice developed DAH with increased pulmonary expression of p53, lincRNA-p21 and cell apoptosis. Intra-pulmonary delivery of shRNA targeting lincRNA-p21 reduced hemorrhage frequencies and improved anemia status through decreasing Bax expression and cell apoptosis. Our findings demonstrate increased p53-dependent lncRNA expression with accelerated cell apoptosis in the lungs of SLE-associated DAH patients, and show the therapeutic potential of targeting intra-pulmonary lncRNA expression in a pristane-induced model of DAH

Estrogen and mechanical loading-related regulation of estrogen receptor-β and apoptosis in tendinopathy.

Female-dominant tendinopathies are musculoskeletal disorders caused by repetitive hand posture and motion; they are considered overuse syndromes. Both external mechanical stress and changes in hormone levels might affect disease progression. We have previously reported that estrogen receptor-β (ER)-β expression was associated with the pathogenesis of de Quervain's disease. To study the underlying mechanisms, a cyclic stretching culture system was applied to tendon tissue from ovariectomized (OVX) rats. Furthermore, a collagenase I-induced rat tendinopathy model was established to examine the association of ER-β with disease progression. Our results showed that ER-β expression and the number of apoptotic cells were higher and associated with disease severity in rats with tendinopathy. Mechanical stress altered the morphology of primary tenocytes and collagen fiber alignment in tendons, and up-regulated the expression of matrix metalloproteinase-9, ER-β, and interleukin-1β, as well as induced apoptosis in tenocytes and tendon tissue from OVX rats. This is the first report on the effects of ER-β and mechanical stress in tendinopathy. We hope these findings contribute to new pharmacological therapies targeting ER-β signaling pathways to treat tendon-related diseases

Balanced and unbalanced reciprocal translocation: An overview of a 30-year experience in a single tertiary medical center in Taiwan

Background: Reciprocal translocation is the most common type of translocation; however, there are only a few studies that address the indications for reciprocal translocation in amniocentesis. Here we share our data, based on 30 years' experience in a single tertiary center, to investigate the rates and indications for amniocentesis in cases of reciprocal translocations. Methods: A retrospective review of 16,749 pregnant women, who underwent midtrimester amniocentesis between January 1981 and December 2010, was conducted. Seventy-four cases of reciprocal translocation were identified. Results: The percentage of reciprocal translocations in all amniocentesis cases was 0.44% (74/16,749); of these 74 cases, 56 were balanced and 18 unbalanced. De novo abnormality occurred in 23 cases, which constituted 31.1% of all reciprocal translocations. The three major indications for amniocentesis with a diagnosis of reciprocal translocation included advanced maternal age (AMA, 52.7%), a parent with an abnormal karyotype (17.6%), and abnormal biochemical markers in the maternal serum (12.2%). For individual types of reciprocal translocations (balanced and unbalanced), except for the presence of abnormal biochemical markers in maternal serum, both AMA and a parent with an abnormal karyotype were primary indications for amniocentesis. However, the highest percentage of reciprocal translocations in all amniocentesis cases was found in cases involving a parent with an abnormal karyotype (5.16%, 13/252). Conclusion: Patients with a parent who carries an abnormal karyotype should be encouraged to undergo amniocentesis in prenatal consultation, since the risk of a diagnosis of reciprocal translocation can be particularly high