Burkitt lymphoma (BL) has been reported to be strongly associated with Epstein-Barr virus (EBV) infection. The fact that EBV is generally present in cancer cells but rarely found in healthy cells represents an opportunity for targeted cancer therapy. One approach is to activate the lytic replication cycle of the latent EBV. Nuclear factor (NF)-κB is thought to play an essential role in EBV lytic infection. Elevated NF-κB levels inhibit EBV lytic replication. Parthenolide (PN) is a sesquiterpene lactone found in medicinal plants, particularly in feverfew ( Tanacetum parthenium ). The aim of the present study was to analyze the effect of PN on the survival of Raji EBV-positive lymphoma cells. Raji cells were treated with 0, 4 or 6 μmol/l PN for 48 h. MTT assay and western blot analysis were performed to evaluate the findings. Results showd that PN suppressed the growth of the EBV-positive BL cell line, Raji, and activated the transcription of BZLF1 and BRLF1 by inhibiting NF-κB activity. Most notably, when PN was used in combination with ganciclovir (GCV), the cytotoxic effect of PN was amplified. These data suggest that the induction of lytic EBV infection with PN in combination with GCV may be a viral-targeted therapy for EBV-associated BL.
The aim of this study was to investigate the effect and mechanism of miR-142-5p/212-5p on the proliferation and collagen formation of cardiac fibroblasts (CFs) after myocardial infarction (MI). The mouse MI model was established by ligation of the left anterior descending coronary artery. CFs were induced by transforming growth factor-beta 1 (TGF-β1) or angiotensin (Ang II). The molecule expressions were measured by qRT-PCR and Western blot. CF proliferation was detected by an MTT assay. The effect of miR-142-5p/212-5p on the luciferase activity of c-Myc 3′UTR was assessed by the luciferase reporter assay. miR-142-5p and miR-212-5p were downregulated in cardiac tissues of MI mice and in TGF-β1- or Ang II-induced CFs, while the protein levels of collagen I and III were upregulated. Moreover, simultaneous overexpression of miR-142-5p/212-5p inhibited the proliferation and collagen formation of TGF-β1- or Ang II-stimulated CFs to a greater extent than either miR-142-5p or miR-212-5p overexpression alone. MiR-142-5p/212-5p targeted c-Myc and negatively regulated its expression. The effects of miR-142-5p/212-5p overexpression on the TP53INP1 protein level and the proliferation and collagen formation of CFs were reversed by c-Myc overexpression. Moreover, overexpression of miR-142-5p/212-5p improved cardiac function and collagen formation of MI mice. Overexpression of miR-142-5p/212-5p cooperatively suppresses the proliferation and collagen formation after MI by regulating c-Myc/TP53INP1.
We previously identified a lipopeptide, EK1C4, by linking cholesterol to EK1, a pan-CoV fusion inhibitory peptide via a polyethylene glycol (PEG) linker, which showed potent pan-CoV fusion inhibitory activity. However, PEG can elicit antibodies to PEG in vivo, which will attenuate its antiviral activity. Therefore, we designed and synthesized a dePEGylated lipopeptide, EKL1C, by replacing the PEG linker in EK1C4 with a short peptide. Similar to EK1C4, EKL1C displayed potent inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses. In this study, we found that EKL1C also exhibited broad-spectrum fusion inhibitory activity against human immunodeficiency virus type 1 (HIV-1) infection by interacting with the N-terminal heptad repeat 1 (HR1) of viral gp41 to block six-helix bundle (6-HB) formation. These results suggest that HR1 is a common target for the development of broad-spectrum viral fusion inhibitors and EKL1C has potential clinical application as a candidate therapeutic or preventive agent against infection by coronavirus, HIV-1, and possibly other class I enveloped viruses.
Purpose: The purpose is to observe the characteristics and perioperative outcomes of fracture in elderly adults with chronic heart failure (CHF).Methods: We searched elderly patients (≥ 65 years) with CHF who developed fracture from January 2017 to February 2021. The gender, age, fracture types, electrocardiogram (ECG), laboratory results, comorbidities, complications, length of hospital stay and mortality of these patients were collected. Risk factors for perioperative cardiovascular disease (CVD) were identified.Results: A total of 104 patients were brought into this study, including 65 female patients (62.5%) and 39 male patients (37.5%). The average age of these patients was 79.5 years old. In those 104 patients, 24 (23.1%) had HFrEF, 49 (47.1%) had HFmrEF, and 31 had HFpEF (29.8%). More than half of the patients had three or more comorbidities, and coronary artery disease was the most common comorbidity (60.6%). The incidence of perioperative CVD and non-cardiac complications was 59.6% and 95.1%, respectively. The mean length of hospital stay was 11.0 (7.0-19.0) days. The in-hospital mortality rate was 4.8%, and 1-year mortality rate was 19.2%. Arrhythmia (40%) was the most common perioperative CVD, and hypoalbuminemia (69.2%) was the most common non-cardiac complication. Multivariate analyses showed that age≥80 years, comorbidities≥3 and hip fracture were associated with increased rates of perioperative CVD.Conclusion: Our results revealed elderly CHF patients with more comorbidities are prone to perioperative CVD after fracture, more comprehensive prevention and integrated management approaches will be required for these patients.
Background: Perioperative transfusion is very common in older patients with hip fracture, but there is still great controversy about whether patients with hemoglobin (Hb) value between 90-100g/L should receive transfusion. The aim of this retrospective study was to observe the curative efficacy of strengthen transfusion strategy for hip fracture patients of age≥65 years.Methods: A retrospective analysis was made on elderly patients with hip fracture who were treated in a single trauma emergency center from 2015 to 2019. Patients who received surgical treatment and had perioperative transfusion records were selected and were divided into three groups according to the lowest perioperative Hb value of 70-80g/L, 80-90g/L and 90-100g/L. According to whether to continue transfusion when the Hb value is between 90-100g/L, they were divided into strengthen transfusion strategy group or routine transfusion strategy group. The demographic data (gender, age, fracture type, complications, etc.), the Hb value, red blood (RBC)use, and patient outcomes between the two groups were analyzed.Results: In total, 4966 elderly hip fracture patients were identified of whom 22.0% had documented perioperative transfusion. After screening the inclusion and exclusion criteria, a total of 802 patients were included in our study, including 95 in the 70-80g /L group, 264 in the 80-90g /L group and 443 in the 90-100g /L group. There was no significant difference in hospital stay between strengthen and routine transfusion group, however strengthen transfusion strategy can reduce the incidence of perioperative pulmonary infection and cerebral infarction in each group. And it can also reduce the incidence of arrhythmia, urinary tract infection in 80-90g /L group and electrolyte disorder in 90-100g /L group, respectively.Conclusions: For elderly patients with hip fracture, strengthen transfusion strategy does not increase the risk of perioperative major adverse coronary events (MACE), reduce the incidence of adverse outcomes such as perioperative pulmonary infection, cerebral infarction and shorten the length of hospital stay.
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