Bradley Grant (playflat4)
Hormone receptor-positive breast cancer accounts for around 75% of breast cancers. The estrogen receptor pathway promotes tumor progression and endocrine resistance. Recently, the cross-talk between the ER signaling pathway and cell cycle regulation has been identified. It is necessary to determine the underlying molecular mechanisms involved in the ER signaling pathway and find new target genes for prognosis and drug resistance in ER+ breast cancer. In this study, lncRNA MAFG-AS1 was shown to be up-regulated and associated with poor prognosis in ER+ breast cancer. Functionally, down-regulation of MAFG-AS1 could inhibit cell proliferation and promote apoptosis. In addition, MAFG-AS1 which contained an estrogen-responsive element could promote CDK2 expression by sponging miR-339-5p. Subsequently, MAFG-AS1 and CDK2 were found to be up-regulated in tamoxifen-resistant MCF-7 cells. Cross-talk between the ER signaling pathway and cell cycle conducted by MAFG-AS1 and CDK2 could promote tamoxifen resistance. In conclusion, our study indicated that estrogen-responsive lncRNA MAFG-AS1 up-regulated CDK2 by sponging miR-339-5p, which promoted ER+ breast cancer proliferation. Cross-talk between the ER signaling pathway and cell cycle suggested that lncRNA MAFG-AS1 is a potential biomarker and therapeutic target in ER+ breast cancer. CDK2 inhibitors may be applied to endocrine resistance therapy.Two new lignans, 3,4-(10-methoxy-phenylallyl)-9″-((10'-isopropanol-3',4'-furan)-phenylacetyl)-8″-dioxane-7″-O-β-d-glucopyranoside (1), 3,4-benzolactone-9″-((12'-isopropanol-3',4'-furan)-phenylbutenone)-8″-dioxane-7″-O-β-d-glucopyranoside (2), and nine known lignan derivatives (3-11) were isolated from the flower buds of Magnolia biondii Pamp. click here for the first time. Their structures were elucidated by 1D and 2D NMR, UV, IR, and MS data, as well as by comparison with those of the references. Compounds (1-11) were evaluated for their neuroprotective activities against 6-OHDA-induced cell death in SH-SY5Y cells. As a result, compounds 1, 2, and 5 exhibited significant neuroprotective activities with IC50 values in the range of 3.08-6.12 μM.The COVID-19 pandemic continues to overwhelm global healthcare systems. While the disease primarily causes pulmonary complications, reports of central nervous system (CNS) involvement have recently emerged ranging from encephalopathy to stroke. This raises a practical dilemma for clinicians as to when to pursue neuroimaging and lumbar tap with cerebrospinal fluid (CSF) analysis in COVID-19 patients with neurological symptoms. We present a case of an encephalopathic patient infected with SARS-CoV-2 with no pulmonary symptoms. We propose a three-tier risk stratification for CNS COVID-19 aiming to help clinicians to decide which patients should undergo CSF analysis. The neurological examination remains an integral component of screening and evaluating patients for COVID-19 considering the range of emerging CNS complications.Background. Common variable immunodeficiency (CVID) is a rare disease characterized by humoral immunodeficiency, often causing sinopulmonary and gastrointestinal infections, and may cause enteropathy in some patients, which leads to severe malnutrition and electrolyte deficiencies. Although many autoimmune diseases are seen with increased frequency in CVID patients, primary hypoparathyroidism is extremely rare.Case presentation. A 50-year-old man with CVID presented with diarrhea. The patient had complaints for 2 years and was cachectic. He had severe electrolyte and vitamin deficiencies that did not respond to oral treatment. The diarrhea causes such as celiac, inflammatory bowel diseases, and gastrointestinal infections were excluded and the endoscopy showed enteropathic changes in the duodenum and colon. Concomitant hypoparathyroidism was also detected in the patient with hypocalcemia despite adequate replacement.Conclusion. Parenteral therapy should be considered in the management of