Exosomes derived from human urine-derived stem cells ameliorate IL-1β-induced intervertebral disk degeneration.

Background: Human intervertebral disk degeneration (IVDD) is a sophisticated degenerative pathological process. A key cause of IVDD progression is nucleus pulposus cell (NPC) degeneration, which contributes to excessive endoplasmic reticulum stress in the intervertebral disk. However, the mechanisms underlying IVDD and NPC degeneration remain unclear.

Pharmaceutical innovation and advanced biotechnology in the biotech-pharmaceutical industry for antibody-drug conjugate development.

Antibody-drug conjugates (ADCs), from prototypes in the 1980s to first- and second-generation products in the 2000s, and now in their multiformats, have progressed tremendously to meet oncological challenges. Currently, 13 ADCs have been approved for medical practice, with over 200 candidates in clinical trials. Moreover, ADCs have evolved into different formats, including bispecific ADCs, probody-drug conjugates, pH-responsive ADCs, target-degrading ADCs, and immunostimulating ADCs.

Percutaneous Mechanical Thrombectomy Using the AcoStream Thrombus Aspiration System for Acute Superior Mesenteric Artery Embolism.

Background: This study was performed to summarize our experience in treating acute superior mesenteric artery embolism (SMAE) by percutaneous mechanical thrombectomy (PMT).

Methods: Between January 2023 and October 2023, 18 patients presenting with acute mesenteric ischemia were admitted to our center, including 11 cases of SMAE, 3 cases of superior mesenteric artery thrombosis, and 4 cases of superior mesenteric vein thrombosis. We retrospectively reviewed 8 patients (4 males and 4 females; range, 51-79 years; mean, 62.

Prediction Model for the Evolution of Residual Stresses and Machining Deformation of Uneven Milling Plate Blanks.

During aerospace thin-walled component processing, the prediction and control of machining deformation have gained increasing attention. The initial residual stress in the blank is a major factor leading to the occurrence of machining deformation. This paper proposes the concept of uneven milling during the workpiece machining process, which is caused by the variation in local cutting depth resulting in uneven material removal thickness.

Musashi-2 binds with Fbxo6 to induce Rnaset2 ubiquitination and chemokine signaling pathway during vascular smooth muscle cell phenotypic switch in atherosclerosis.

Objective: The objective of this study is to determine how Musashi-2 (MSI2) affects vascular smooth muscle cell (VSMC) phenotypic switch and contributes to atherosclerosis (AS).

Methods: Primary mouse VSMCs were transfected with MSI2 specific siRNA and treated with platelet-derived growth factor-BB (PDGF-BB). The proliferation, cell-cycle, and migration of VSMCs were determined by CCK-8, flow cytometry, wound healing, and transwell assays.

Integration of GWAS and RNA-Seq Analysis to Identify SNPs and Candidate Genes Associated with Alkali Stress Tolerance at the Germination Stage in Mung Bean.

Soil salt-alkalization seriously impacts crop growth and productivity worldwide. Breeding and applying tolerant varieties is the most economical and effective way to address soil alkalization. However, genetic resources for breeders to improve alkali tolerance are limited in mung bean.

Microfibrillar-associated protein 5 suppresses adipogenesis by inhibiting essential coactivator of PPARγ.

Femoral head necrosis is responsible for severe pain and its incidence is increasing. Abnormal adipogenic differentiation and fat cell hypertrophy of bone marrow mesenchymal stem cells increase intramedullary cavity pressure, leading to osteonecrosis. By analyzing gene expression before and after adipogenic differentiation, we found that Microfibril-Associated Protein 5 (MFAP5) is significantly down-regulated in adipogenesis whilst the mechanism of MFAP5 in regulating the differentiation of bone marrow mesenchymal stem cells is unknown.

RON Receptor Tyrosine Kinase in Tumorigenic Stemness as a Therapeutic Target of Antibody-drug Conjugates for Eradication of Triple-negative Breast Cancer Stem Cells.

Background: Cancer stem-like cells in triple-negative breast cancer (TNBC-SLCs) are the tumorigenic core for malignancy. Aberrant expression of the RON receptor tyrosine kinase has implications in TNBC tumorigenesis and malignancy.

Objective: In this study, we identified the RON receptor as a pathogenic factor contributing to TNBC cell stemness and validated anti-RON antibody-drug conjugate Zt/g4-MMAE for eradication of RONexpressing TNBC-SLCs.

miR-219a-5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3.

Purpose: This work was to identify the function and mechanism of miR-219a-5p in regulating knee osteoarthritis (KOA).

Methods: Rat fibroblast-like synoviocytes (FLSs) were isolated to construct KOA cell model by lipopolysaccharide and adenosine triphosphate treatment. miR-219a-5p and FBXO3 expression in FLSs was modulated by transfection.

Al-doped α-MnO coated by lignin for high-performance rechargeable aqueous zinc-ion batteries.

Zn/MnO batteries, one of the most widely studied rechargeable aqueous zinc-ion batteries, suffer from poor cyclability because the structure of MnO is labile with cycling. Herein, the structural stability of α-MnO is enhanced by simultaneous Al doping and lignin coating during the formation of α-MnO crystals in a hydrothermal process. Al enters the [MnO] octahedron accompanied by producing oxygen vacancies, and lignin further stabilizes the doped Al strong interaction in the prepared material, Al-doped α-MnO coated by lignin (L + Al@α-MnO).

The Association between Dietary Protein Intake and the Risk of Pancreatic Cancer: Evidence from 14 Publications.

Many studies have been published to assess the association about dietary protein intake on the risk of pancreatic cancer, but with inconsistent result. This meta-analysis aimed to evaluate whether protein intake could affect the risk of pancreatic cancer. A systematic literature search was performed in PubMed, EMBASE and Web of Science up to October 1, 2019.

Dok5 regulates proliferation and differentiation of osteoblast via canonical Wnt/β-catenin signaling.

Objective: In bone tissue engineering, the use of osteoblastic seed cells has been widely adopted to mediate the osteogenic differentiation so as to prompt bone regeneration and repair. It is hypothesized that Dok5 can regulate the proliferation and differentiation of osteoblasts. In this study, the role of Dok5 in osteoblast proliferation and differentiation was investigated.

Thrap3 promotes osteogenesis by inhibiting the degradation of Runx2.

The dysfunction of osteogenesis is a key character in the pathogenesis of osteoporosis, but the network of signaling mechanisms in controlling the differentiation of osteoblast remain unclear. Thrap3 has been proved participating in various biological process, especially in the differentiation of stem cells. Here, we demonstrate that Thrap3 could promote osteogenesis through the inhibition of the degradation of Runx2, which is a key molecular structure in early osteoblast differentiation.

Antibody-drug Conjugate PCMC1D3-Duocarmycin SA as a Novel Therapeutic Entity for Targeted Treatment of Cancers Aberrantly Expressing MET Receptor Tyrosine Kinase.

Background: Aberrant expression of the MET receptor tyrosine kinase is an oncogenic determinant and a drug target for cancer therapy. Currently, antibody-based biotherapeutics targeting MET are under clinical trials.

Objective: Here, we report the preclinical and therapeutic evaluation of a novel anti-MET antibody- drug conjugate PCMC1D3-duocarmycin SA (PCMC1D3-DCM) for targeted cancer therapy.

Microfibrillar-associated protein 5 regulates osteogenic differentiation by modulating the Wnt/β-catenin and AMPK signaling pathways.

Background: Dysfunctional osteogenesis of bone marrow mesenchymal stem cells (BMSCs) plays an important role in osteoporosis occurrence and development. However, the molecular mechanisms of osteogenic differentiation remain unclear. This study explored whether microfibrillar-associated protein 5 (MFAP5) regulated BMSCs osteogenic differentiation.

IARS2 regulates proliferation, migration, and angiogenesis of human umbilical vein endothelial cells.

Objective: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism.

Methods: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis.

Duocarmycin-based antibody-drug conjugates as an emerging biotherapeutic entity for targeted cancer therapy: Pharmaceutical strategy and clinical progress.

Duocarmycins are a class of DNA minor-groove-binding alkylating molecules. For the past decade, various duocarmycin analogues have been used as payloads in the development of antibody-drug conjugates (ADCs). Currently, more than 15 duocarmycin-based ADCs have been studied preclinically, and some of them such as SYD985 have been granted Fast-Track Designation status.

Combination of Neutrophil-to-Lymphocyte Ratio and Admission Glasgow Coma Scale Score Is Independent Predictor of Clinical Outcome in Diffuse Axonal Injury.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of clinical outcome of different diseases, such as acute ischemic stroke, intracerebral hemorrhage, malignant tumor, and traumatic brain injury. However, the prognostic value of NLR plus admission Glasgow Coma Scale score (NLR-GCS) is still unclear in patients with diffuse axonal injury (DAI). Therefore this study assessed the relationship between the NLR-GCS and 6-month outcome of DAI patients.

Oncogenic mechanism-based pharmaceutical validation of therapeutics targeting MET receptor tyrosine kinase.

Aberrant expression and/or activation of the MET receptor tyrosine kinase is characterized by genomic recombination, gene amplification, activating mutation, alternative exon-splicing, increased transcription, and their different combinations. These dysregulations serve as oncogenic determinants contributing to cancerous initiation, progression, malignancy, and stemness. Moreover, integration of the MET pathway into the cellular signaling network as an addiction mechanism for survival has made this receptor an attractive pharmaceutical target for oncological intervention.

Bioinformatics analysis of miRNA and mRNA expression profiles to reveal the key miRNAs and genes in osteoarthritis.

Background: Osteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis. This study aimed to identify the key miRNAs and genes associated with OA progression.

Methods: The GSE105027 (microRNA [miRNA/miR] expression profile; 12 OA samples and 12 normal samples) and GSE48556 (messenger RNA [mRNA] expression profile; 106 OA samples and 33 normal samples) datasets were selected from the Gene Expression Omnibus database.

Pathological significance of abnormal recepteur d'origine nantais and programmed death ligand 1 expression in colorectal cancer.

Background: Programmed death ligand 1 (PD-L1) immunotherapy remains poorly efficacious in colorectal cancer (CRC). The recepteur d'origine nantais (RON) receptor tyrosine kinase plays an important role in regulating tumor immunity.

Aim: To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC.

Pharmaceutical strategies in the emerging era of antibody-based biotherapeutics for the treatment of cancers overexpressing MET receptor tyrosine kinase.

Pharmaceutical innovation in the development of novel antibody-based biotherapeutics with increased therapeutic indexes makes MET-targeted cancer therapy a clinical reality.