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Long non-coding RNA steroid receptor RNA activator (lncRNA-SRA) has been proven to regulate vascular smooth muscle cell (VSMC) proliferation, indicating its possible involvement in cardiovascular disease. Diabetes is a major cause of cardiovascular disease. The aim of the present study was to investigate the involvement of lncRNA-SRA in type II diabetic cardiovascular disease. The plasma levels of lncRNA-SRA were identified to be significantly lower in patients with type II diabetic cardiovascular disease compared with those in type II diabetic patients without any obvious complications and in healthy controls. A 5-year follow-up study revealed that low vs. high expression levels of lncRNA-SRA were associated with an increased incidence of cardiovascular disease in type II diabetic patients. High-glucose treatment did not significantly affect the expression of lncRNA-SRA in human VSMCs in vitro. However, ectopic overexpression of lncRNA-SRA increased the viability of human VSMCs in a high-glucose environment. It was concluded that downregulation of lncRNA-SRA may participate in the development of cardiovascular disease in type II diabetic patients. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is clinically divided into unicentric CD (UCD) and multicentric CD (MCD). Hyaline-vascular variant (HV) is the most common pathological type of UCD, while the plasma cell type (PC) is the most common type of MCD and thus, hyaline-vascular variant multicentric CD (HV-MCD) is a rare type of CD. In addition, its etiology has remained elusive. The present study retrospectively analyzed the medical records of 3 patients diagnosed as HV-MCD admitted to The First Affiliated Hospital of Guangxi Medical University (Guangxi, China) between January 2007 and September 2020. A total of 2 males and 1 female were admitted. The areas involved varied considerably. Respiratory symptoms were seen in 3 cases, along with fever, weight loss and splenomegaly. Damage to the skin and mucous membranes resulted in oral ulcers when accompanied by paraneoplastic pemphigus (PNP). Dry and wet rales were found in all patients. All 3 cases were complicated with PNP and had hypoxemia and obstructive ventilation dysfunction. In accordance with PC-MCD, it manifested as lymph node enlargement and may involve several lymph nodes. Computed tomography mainly indicated bronchiectasis and mediastinal lymph node enlargement. In 1 case, chemotherapy failed after local mass excision, 1 case remitted after chemotherapy but the lung lesion was irreversible and 1 case was untreated and soon died of respiratory failure. The cases of HV-MCD with pulmonary involvement were induced by small airway lesions and associated with poor prognosis. Respiratory symptoms along with systemic symptoms were common. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is a major challenge for the management of the majority of cancers. The precise molecular mechanisms of MDR remain elusive. In a previous study, a multidrug resistant osteosarcoma model [MG63/vincristine (VCR)] was established by intermittent exposure of MG63 cells to gradually increasing concentrations of VCR. These cells exhibited cross-resistance to multiple structurally and mechanistically unrelated chemotherapeutic agents. The development of MDR was associated with increased expression of LIM kinase 1 (LIMK1). Compared with that in normal human fetal osteoblasts (hFOB) 1.19, the messenger RNA and protein expression of LIMK1 was significantly elevated both in MG63 and U2OS osteosarcoma cells. To observe the expression pattern of LIMK1 in osteosarcoma, immunohistochemical analyses were performed on specimens derived from 6 patients. The results indicated that LIMK1 was expressed to a greater extent in the tumor parenchyma than in the mesenchyme. The role of LIMK1 in MDR was confirmed by transfecting plasmids coding LIMK1-small interfering RNA (siRNA), wild-type-LIMK1 or empty vector into MG63/VCR cells, and measuring the expression of LIMK1 and multidrug resistance protein 1 (MDR1), also known as P-gycoprotein (P-gp). The results demonstrated that the level of MDR1/P-gp was positively correlated with the level of LIMK1. This correlation was also shown with the doxorubicin efflux assay and by measuring apoptosis. Specifically, after 6 h of incubation with VCR, 25.6% of the cells transfected with the LIMK1-siRNA plasmid were apoptotic compared with 6.2% in the empty vector group and 1.3% in the group of cells transfected with the wild-type-LIMK1 plasmid. Thus, it was concluded that LIMK1 serves a key role in the MDR of osteosarcoma and functions through MDR1. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is a challenge for the treatment of cancer and the underlying molecular mechanisms remain elusive. The current study exposed MG63 osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish four VCR-resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug resistance indices (RI) of these sublines was detected with the CCK-8 assay and determined to be163, 476, 1,247, and 2,707-fold higher than that of parental cells, respectively. These sublines also exhibited cross-resistance to doxorubicin, paclitaxel and pirarubicin. With increased RI, the proliferative capacity of these sublines was gradually reduced and cell morphology was also altered, characterized by increased formation of pseudopodia and long cytoplasmic processes at opposite poles. However, the migration capacity and expression of certain drug resistance-associated genes were not in accordance with the increased RI; multidrug resistance protein 1 (MDR1) expression was significantly increased in these sublines compared with parental cells. However, in the highly resistant MG63/VCR3 and MG63/VCR4 cells, MDR-associated protein 1, topoisomerase II and LIM domain kinase 1 levels were significantly reduced compared with the moderately resistant MG63/VCR2 cells. Expression of glutathione S-transferase-⨅ mRNA was determined using reverse transcription-quantitative polymerase chain reaction and determined that it was not changed between MG63 and MG63/VCR cells. The data of the present study demonstrated that the molecular alterations of drug resistance may change with the degree of drug resistance. Taking cell morphology into consideration, the intratumor clonal and phenotypic heterogeneity may be responsible for drug resistance. These MG63/VCR sublines may be a valuable tool to assess drug resistance and the underlying mechanisms, and to identify novel drug resistance-associated genes or strategies to overcome MDR in human osteosarcoma. [ABSTRACT FROM AUTHOR]

Evodiamine (Evo) is an alkaloid that can be extracted from the berry fruit Evodia rutaecarpa and has been reported to exert various pharmacological effects, such as antidiarrheal, antiemetic and antiulcer effects. In vivo, the potential effects of Evo were investigated in a mouse model of dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and in adenomatous polyposis coli (Apc)MinC/Gpt C57BL/6 mice with colorectal cancer (CRC), where the latter harbours a point-mutation in the Apc gene. Evo suppressed the degree of weight loss and colon shortening induced by DSS, decreased the disease activity index value and ameliorated the pathological alterations in the colon of mice with UC as examined via H&E staining of colon tissues. In addition, Evo decreased the number and size of colonic tumors in ApcMinC/Gpt mice. Proteomics (colon tissues), ELISA (colon tissues and serum) and western blotting (colon tissues) results revealed that Evo inhibited NF-κB to mediate the levels of various cytokines, including, in the DSS-induced UC model, IL-1β, IL-2, IL-6, IL-8, TNF-α, IFN-γ (ELISA of colon tissues and serum), NF-κB, IKKα+β, IκBα, S100a9, TLR4 and MyD88 (western blotting of colon tissues), and, in the colorectal cancer model, IL-1β, IL-2, IL-6, IL-15, IL-17, IL-22, TNF-α (ELISA of colon tissues and serum), NF-κB, IKKα+β, IκBα and S100a9 (western blotting of colon tissues), to achieve its anti-inflammatory and antitumor effects. In vitro, Evo also reduced the viability of the colon cancer cell line SW480, inhibited mitochondrial membrane potential (MMP detection), caused G2/M-phase arrest (cell cycle detection) and suppressed the translocation of phosphorylated-NF-κB from the cytoplasm into the nucleus (immunofluorescence of p-NF-κB). Theoretical evidence (MD simulations) suggest that Evo may bind to the ordered domain (α-helix) of NF-κB to influence this protein. The protein secondary structure changes were analyzed by the cpptraj module in Amber. In addition, these data provide experimental evidence that Evo may be an effective agent for treating UC and CRC. [ABSTRACT FROM AUTHOR]