Safety evaluation of tucatinib: Adverse event signal mining and analysis based on the FAERS database.

The purpose of this study was to evaluate the adverse events (AEs) associated with tucatinib by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and explore potential drug-related AEs, thereby guiding safe clinical use.

Comparative study of total-body PET and PET/MR in the diagnosis of liver metastases.

Objective: To compare the diagnostic differences between total-body PET/CT (positron emission tomography/computed tomography) and PET/MR (positron emission tomography/magnetic resonance) in detecting liver metastases.

Methods: The study analyzed data from patients with malignancies who underwent both conventional total-body PET/CT and liver PET/MR imaging between June 2020 and December 2020. A total of 20 patients with confirmed liver metastases were included, 9 of whom also underwent 2-hour delayed imaging of the liver.

Regional and longitudinal dynamics of human milk protein components assessed by proteome analysis on a fast and robust micro-flow LC-MS/MS system.

An in-depth exploration of molecular composition of human milk could provide a scientific basis for the development of substitutes. The present study was conducted to analyze human milk proteins from 110 individuals from five regions of China and across three stages of lactation to investigate the change patterns. We developed a micro-flow liquid chromatography tandem mass spectrometry (μLC-MS/MS) system with data-independent acquisition (DIA) proteomics technology that can rapidly and stably characterize the human milk proteome.

A Novel Scale System Based on the Frailty Index and Laboratory Indicators for the Short-Term Prognosis of Patients with Acute Myocardial Infarction: A Retrospective Cohort Study.

Objective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI.

Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included.

Components of the JNK-MAPK pathway play distinct roles in hepatocellular carcinoma.

Purpose: Mitogen-activated protein kinases (MAPK), specifically the c-Jun N-terminal kinase (JNK)-MAPK subfamily, play a crucial role in the development of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of JNK1/2 and their upstream regulators, MKK4/7, in HCC carcinogenesis remain unclear.

Methods: In this study, we performed differential expression analysis of JNK-MAPK components at both the transcriptome and protein levels using TCGA and HPA databases.

Integrative proteomics and n-glycoproteomics reveal the synergistic anti-tumor effects of aspirin- and gemcitabine-based chemotherapy on pancreatic cancer cells.

Objective And Design: Pancreatic cancer is a highly malignant tumor that is well known for its poor prognosis. Based on glycosylation, we performed integrated quantitative N-glycoproteomics to investigate the synergistic anti-tumor effects of aspirin and gemcitabine on pancreatic cancer cells and explore the potential molecular mechanisms of chemotherapy in pancreatic cancer.

Methods And Results: Two pancreatic cancer cell lines (PANC-1 and BxPC-3) were treated with gemcitabine, aspirin, and a combination (gemcitabine + aspirin).

Intranasal inoculation of female BALB/c mice with replication-deficient human adenovirus type 5 expressing SARS-CoV-2 nucleocapsid protein aggravates lung pathology upon re-encountering the antigen.

Preclinical studies indicate that SARS-CoV-2 nucleocapsid (N)-based vaccines, along with other viral protein(s), confer protection in various animal models against infection by SARS-CoV-2 ancestral virus and variants of concern. However, the optimal vaccination procedure and the role of N-specific host adaptive immune responses remain elusive. Here, we report that intranasal inoculation with replication-deficient human adenovirus type 5 expressing SARS-CoV-2 N protein (Ad5-N) conferred no protection in the lung of female BALB/c mice upon re-encountering the antigen, either by 10-fold Ad5-N re-exposure or sublethal infection of mouse-adapted SARS-CoV-2.

Fluoxetine partially alleviates inflammation in the kidney of socially stressed male C57 BL/6 mice.

Stress-related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress-induced changes in the renal transcriptome associated with the development of depressive behaviors, we generated here a chronic social defeat stress (CSDS) model of C57 BL/6 male mice and then performed RNA sequencing of the kidneys to obtain an inflammation-related transcriptome. Administration of the antidepressant drug fluoxetine (10 mg·kg ·day ) during CSDS induction could partially alleviate renal inflammation and reverse CSDS-induced depression-like behaviors.

Clinical efficacy analysis of mesenchymal stem cell therapy in patients with COVID-19: A systematic review.

Background: Currently, ongoing trials of mesenchymal stem cells (MSC) therapies for coronavirus disease 2019 (COVID-19) have been reported.

Aim: In this study, we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients.

Methods: Search terms included stem cell, MSC, umbilical cord blood, novel coronavirus, severe acute respiratory syndrome coronavirus-2 and COVID-19, applied to PubMed, the Cochrane Controlled Trials Register, EMBASE and Web of Science.

The G4 Resolvase DHX36 Possesses a Prognosis Significance and Exerts Tumour Suppressing Function Through Multiple Causal Regulations in Non-Small Cell Lung Cancer.

Lung cancer is one of the most prevalent cancers in both men and women worldwide. The nucleic acid G4 structures have been implicated in the transcriptional programmes of cancer-related genes in some cancers such as lung cancer. However, the role of the dominant G4 resolvase DHX36 in the progression of lung cancer remains unknown.

Development of an antibody-dependent cellular cytotoxicity reporter assay for measuring anti-Middle East Respiratory Syndrome antibody bioactivity.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a highly virulent pathogen that causes Middle East Respiratory Syndrome (MERS). Anti-MERS-CoV antibodies play an integral role in the prevention and treatment against MERS-CoV infections. Bioactivity is a key quality attribute of therapeutic antibodies, and high accuracy and precision are required.

The incidence of cytokine release syndrome and neurotoxicity of CD19 chimeric antigen receptor-T cell therapy in the patient with acute lymphoblastic leukemia and lymphoma.

Our objective was to summarize the side effect of chimeric antigen receptor (CAR)-T cell therapy in patients with acute lymphocytic leukemia (ALL) and lymphoma. Two independent reviewers extracted relevant data. A total of 35 hematologic malignancy studies with CD19 CAR-T cell were included (1412 participants).

A robust and stable reporter gene bioassay for anti-IgE antibodies.

Immunoglobin E (IgE)-related allergy constitutes a high proportion in allergic diseases. The production of specific IgE is key to evoking serial cascades and pathological reactions. Thus, targeting IgE is a different therapeutic approach from symptomatic treatments.

Assessment of the efficacy of passive cellular immunotherapy for glioma patients.

To evaluate the therapeutic efficacy of passive cellular immunotherapy for glioma, a total of 979 patients were assigned to the meta-analysis. PubMed and the Cochrane Central Register of Controlled Trials were searched initially from February 2018 and updated in April 2019. The overall survival (OS) rates and Karnofsky performance status (KPS) values of patients who underwent passive cellular immunotherapy were compared to those of patients who did not undergo immunotherapy.

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies.

Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proved remarkably effective in recently published clinical trials. In this meta-analysis, we performed a systematic review in terms of the clinical response treated with CAR-T cells in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and lymphomas patients. Thirty-eight published clinical studies including 665 patients were eligible for response rate (RR) evaluation.

RACK1 Promotes Self-Renewal and Chemoresistance of Cancer Stem Cells in Human Hepatocellular Carcinoma through Stabilizing Nanog.

Targeting cancer stem cells (CSCs) has been proposed as a new strategy to eradicate malignancies, including hepatocellular carcinoma (HCC). However, the mechanisms by which CSCs sustain their self-renewal and chemoresistance remain elusive. Nanog is a master transcriptional regulator of stemness, especially in CSCs.

Measuring the bioactivity of anti-IL-6/anti-IL-6R therapeutic antibodies: presentation of a robust reporter gene assay.

IL-6 has an important role in the pathogenesis of autoimmunity and chronic inflammation. Several mAbs that target IL-6 or the IL-6 receptor (IL-6R) have been established and approved for the treatment of various diseases such as multicentric Castleman's disease and rheumatoid arthritis. Quality control of therapeutic antibodies requires accurate determination of bioactivity.

Development of a robust reporter gene based assay for the bioactivity determination of IL-5-targeted therapeutic antibodies.

Eosinophilic asthma is characterized by the eosinophilic inflammation with the allergen independent activation of Th2 lymphocytes. Since IL-5 plays an important role in the maturation, survival and migration of eosinophils, hence the pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5Rα have been developed and/or marketed, including Mepolizumab, Reslizumab, and Benralizumab. Accurate determination of bioactivity is crucial for the safety and efficacy of therapeutic antibodies.

Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells.

Smad4 is a common Smad and is a key downstream regulator of the transforming growth factor-β signaling pathway, in which Smad4 often acts as a potent tumor suppressor and functions in a highly context-dependent manner, particularly in pancreatic cancer. However, little is known regarding whether Smad4 regulates other signaling pathways involved in pancreatic cancer. The present study demonstrated that Smad4 downregulates c-Jun N-terminal kinase (JNK) activity using a Smad4 loss-of-function or gain-of-function analysis.

The NEDD8-activating enzyme inhibitor MLN4924 induces G2 arrest and apoptosis in T-cell acute lymphoblastic leukemia.

The first-in-class compound MLN4924 is a small molecule inhibitor that selectively inactivates NEDD8-activating enzyme (NAE). The anticancer effects of MLN4924 have been attributed to impaired neddylation of Cullin proteins. Here, we show that treatment of T-cell acute lymphoblastic leukemia (T-ALL) cells with MLN4924 potently suppressed the neddylation of Cullins and the oncogenic growth of T-ALL cells in-vitro.

RACK1 Promotes Autophagy by Enhancing the Atg14L-Beclin 1-Vps34-Vps15 Complex Formation upon Phosphorylation by AMPK.

Autophagy is essential for maintaining tissue homeostasis. Although adaptors have been demonstrated to facilitate the assembly of the Atg14L-Beclin 1-Vps34-Vps15 complex, which functions in autophagosome formation, it remains unknown whether the autophagy machinery actively recruits such adaptors. WD40-repeat proteins are a large, highly conserved family of adaptors implicated in various cellular activities.

Validity of combination active specific immunotherapy for colorectal cancer: a meta-analysis of 2993 patients.

Background Aims: The aim of this study was to investigate whether active specific immunotherapy (ASI) is able to demonstrate therapeutic efficacy against colorectal cancer.

Methods: We conducted a systematic review of published papers from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors who used predefined database templates.

RACK1 antagonizes TNF-α-induced cell death by promoting p38 activation.

p38 mitogen-activated protein kinase (MAPK) activity has been reported to either promote or suppress cell death, which depends on cell type and stimulus. Our previous report indicates that p38 exerts a protective role in tumor necrosis factor (TNF)-α-induced cell death in L929 fibroblastoma cells. However, key molecules regulating p38 activation remain unclear.

Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis.

Objectives: Our meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of tumour vaccines for the treatment of advanced non-small cell lung cancer (NSCLC).

Design: Systematic review and meta-analysis of randomised controlled trials (RCT).

Data Sources: PubMed, the Cochrane Center Register of Controlled Trials, Science Direct and EMBASE were searched from January 1980 until January 2015.

Clinical efficacy of autologous stem cell transplantation for the treatment of patients with type 2 diabetes mellitus: a meta-analysis.

Background Aims: In this study, we investigate whether bone marrow mononuclear cells (BM-MNC) or peripheral blood mononuclear cells (PB-MNC) have therapeutic efficacy in type 2 diabetes (T2D).

Methods: Search terms included stem cell, bone marrow cell, peripheral blood cell, umbilical cord blood and T2D in MEDLINE, the Cochrane Controlled Trials Register, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net.

Results: Fifteen trials met our inclusion criteria (n = 497).