Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays important ...roles in several cellular functions such as infiltration, migration, and motility. We report significantly higher levels of CXCL13 expression in collagen-induced arthritis (CIA) mice compared with controls and also in synovial fluid from RA patients compared with human osteoarthritis (OA) samples. RA synovial fluid increased endothelial progenitor cell (EPC) homing and angiogenesis, which was blocked by the CXCL13 antibody. By interacting with the CXCR5 receptor, CXCL13 facilitated vascular endothelial growth factor (VEGF) expression and angiogenesis in EPC through the PLC, MEK, and AP-1 signaling pathways. Importantly, infection with CXCL13 short hairpin RNA (shRNA) mitigated EPC homing and angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with CIA. CXCL13 is therefore a novel therapeutic target for RA.
In 2019, Taiwan became the first country in Asia to legalize same-sex marriage. Celebrated as a victory for global lesbian, gay, bisexual, and transgender (LGBT) rights, Taiwan’s 2019 law privileges ...marriage and biological parent-child ties as the foundation for LGBT family rights and (co-)parental recognition. This article contributes to sociolegal debates about the benefits and limitations of marriage equality by asking how restrictive legal approaches to legitimating LGBT parenthood may harm LGBT families, with consequences both for families ostensibly protected under the new laws and for those denied newly bestowed rights and protections. Drawing from legal and ethnographic research on Taiwan’s same-sex marriage law and the family formation strategies of Taiwanese LGBT parents, we interrogate how marriage equality interacts with related legal domains and prevailing stigmas of illegitimacy, adoption, and homosexuality in Taiwan. Encoded in, and reproduced through, the substance and implementation of law, these stigmas narrow the scope of legal rights and foster potentially discriminatory forms of recognition. The article shows how progressive laws may reduce LGBT family stigma for some, while also creating new stigma interactions that devalue diverse forms of LGBT parenthood.
In 2017, Taiwan's Constitutional Court issued a decision ruling the same-sex marriage ban unconstitutional. Celebrated as a victory for marriage equality readying Taiwan to become "the first in Asia" ...to legalize same-sex marriage, the decision's reasoning demonstrated a remarkable resemblance to 'Obergefell v. Hodges' in that they both embrace formal equality, endorse marital supremacy, and render feminist critique of marriage irrelevant or insignificant. Through an investigation of social movement dynamics and constitutional politics, this Article explores the hidden histories of marriage equality and the rise of marital supremacy, revealing how marriage equality has served as a site of contestation where various visions of equality compete and where legal orientalism is enacted as well as resisted. It argues that Taiwan's Constitutional Court decision and the marriage equality movement demonstrate a case of migrating marriage equality without feminism, presenting challenges for transnational feminism in terms of its absence.
The #MeToo movement gained global prominence after Hollywood celebrities came forward with their experiences of sexual violence and encouraged others to do the same. This was by no means the first ...time a woman had told the world of her experience of sexual violation, but this time, the powerful were paying attention: “Women have been saying these things forever. It is the response to them that has changed” (MacKinnon 2020, 7). High-quality investigative journalists vetted the women's accounts and provided more stories of sexual abuse and predation. Many survivors have since come forward with their own names and their perpetrators’ names, leading some prominent men to be deprived of their fame and positions of power. The #MeToo movement makes two things matter and count: what the victims say and what the perpetrators did. It has raised the perpetrators’ accountability and the victims’ credibility and reversed the scenario of sexual violation: making the perpetrator, not the victim, pay for the sexual harm.
Epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) are currently the most effective treatment for non-small cell lung cancer (NSCLC) patients, who carry primary EGFR mutations. However, ...the patients eventually develop drug resistance to EGFR-TKIs after approximately one year. In addition to the acquisition of the EGFR T790M mutation, the activation of alternative receptor-mediated signaling pathways is a common mechanism for conferring the insensitivity of EGFR-TKI in NSCLC. Upregulation of the Mer receptor tyrosine kinase (MERTK), which is a member of the Tyro3-Axl-MERTK (TAM) family, is associated with a poor prognosis of many cancers. The binding of specific ligands, such as Gas6 and PROS1, to MERTK activates phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) cascades, which are the signaling pathways shared by EGFR. Therefore, the inhibition of MERTK can be considered a new therapeutic strategy for overcoming the resistance of NSCLC to EGFR-targeted agents. Although several small molecules and monoclonal antibodies targeting the TAM family are being developed and have been described to enhance the chemosensitivity and converse the resistance of EGFR-TKI, few have specifically been developed as MERTK inhibitors. The further development and investigation of biomarkers which can accurately predict MERTK activity and the response to MERTK inhibitors and MERTK-specific drugs are vitally important for obtaining appropriate patient stratification and increased benefits in clinical applications.
Imbalance of lipid metabolism is a main cause of metabolic syndrome leading to life-threatening metabolic diseases. Angiopoietin-like protein 8 (Angptl8) was recently identified as a liver and ...adipose tissue-released hormone that is one of the molecules involved in triglyceride metabolism. However, the regulatory mechanism of Angptl8 is largely unknown. A high fat diet (HFD)-fed mouse model, which showed high cholesterol, high triglyceride, and high insulin in the blood, revealed the upregulation of hepatic and plasma Angptl8 and the downregulation of hepatic glycine
-methyltransferase (GNMT). The inverse correlation of hepatic Angptl8 and GNMT expression in the livers of HFD-fed mice was also confirmed in a publicly available microarray dataset. The mechanistic study using primary hepatocytes showed that the Angptl8 expression could be induced by insulin treatment in a dose- and time-dependent manner. Inhibition of PI3K/Akt pathway by the specific inhibitors or the dominant-negative Akt blocked the insulin-induced Angptl8 expression. Moreover, knockout of GNMT promoted the Akt activation as well as the Angptl8 expression. These results suggested that GNMT might be involved in insulin-induced Angptl8 expression in HFD-mediated metabolic syndrome.
The twenty-first century has witnessed the rise of a new constitutional jurisprudence of marriage which extends the institution of marriage to include same-sex couples in the name of equality, ...freedom, and dignity, and an accompanying trend of constitutionalizing marital supremacy. Progressive critics have voiced against the constitutional treatment of marriage as the ideal family form, proposing various approaches to promote equality for diverse families. The inequality of single women without children, however, has not yet received the attention that it deserves in the jurisprudence of non-marriage, despite the globally growing phenomenon of women opting out of marriage and other formal unions and living a legally single life. It is argued that the move beyond marriage equality must include the pursuit of single equality, that is, equal citizenship unmediated by marital, relational, family, or parental status. It is suggested that a feminist agenda of single equality is needed even more, and that public laws' active role is required to facilitate single equality.
Lung cancer patients with human immunodeficiency virus (HIV) have a poorer prognosis than do patients without HIV infection. HIV1 Tat is a secreted viral protein that penetrates the plasma membrane ...and interacts with a number of proteins in non‐HIV‐infected cells. The loss of function of Tat‐interacting protein 30 (TIP30) has been linked to metastasis in non‐small cell lung cancer (NSCLC). However, it is unknown how the interaction of HIV1 Tat with TIP30 regulates the metastasis of NSCLC cells. In this study, the overexpression of TIP30 decreased tumor growth factor‐β‐induced epithelial‐to‐mesenchymal transition (EMT) and invasion of NSCLC cells, whereas the knockdown of TIP30 promoted EMT, invasion and stemness. Exposure to recombinant HIV1 Tat proteins promoted EMT and invasion. A mechanistic study showed that the interaction of HIV1 Tat with TIP30 blocked the binding of TIP30 to importin‐β, which is required for the nuclear translocation of Snail. Indeed, the loss of TIP30 promoted the nuclear translocation of Snail. In vivo studies demonstrated that the overexpression of TIP30 inhibited the metastasis of NSCLC cells. In contrast, the coexpression of HIV1 Tat and TIP30 diminished the inhibitory effect of TIP30 on metastasis. Immunohistochemistry confirmed that TIP30 overexpression reduced the nuclear localization of Snail, whereas the coexpression of HIV1 Tat and TIP30 increased nuclear Snail in metastatic tumors. In conclusion, the binding of HIV1 Tat to TIP30 enhanced EMT and metastasis by regulating the nuclear translocation of Snail. Targeting Tat‐interacting proteins may be a potential therapeutic strategy to prevent metastasis in NSCLC patients with HIV infection.
TIP30 competes with Snail for the binding to importin‐β and inhibits the nuclear translocation of Snail, which promotes EMT and invasion ability of cancer cells. Binding of HIV1 Tat to TIP30 blocks the interaction between TIP30 and importin‐β, leading to the increase of Snail nuclear translocation, invasion and distant metastasis of NSCLC cells.
Two plasmids carrying blaNDM-1 isolated from carbapenem-resistant Klebsiella pneumoniae (CR-KP) and carbapenem-resistant Escherichia coli (CR-EC) were sequenced. CR-KP and CR-EC were isolated from ...two Taiwanese patients without travel histories.
Complete sequencing of the plasmids (pLK75 and pLK78) was conducted using a shotgun approach. Annotation of the contigs was performed using the RAST Server, followed by manual inspection and correction.
These similar plasmids were obtained from two patients with overlapping stays at the same hospital. The pLK75 and pLK78 plasmids were 56,489-bp and 56,072-bp in length, respectively. Plasmid annotation revealed a common backbone similar to the IncN plasmid pR46. The regions flanking the blaNDM-1 genes in these plasmids were very similar to plasmid pNDM-HU01 in Japan, which contains a complex class 1 integron located next to an ISCR1 element. The ISCR1 element has been suggested to provide a powerful mechanism for mobilising antibiotic resistance genes.
Two indigenous NDM-1-producing Enterobacteriaceae cases were identified for the first time in Taiwan, highlighting the alarming introduction of NDM-1-producing Enterobacteriaceae in this region.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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