Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (FL) is indicated after progression on gemcitabine-based therapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). However, salvage therapy after nal-IRI/FL failure remains to be established.
Methods: This study included 260 consecutive patients who initiated nal-IRI/FL therapy reimbursed by the National Health Insurance of Taiwan between January 2019 and March 2023.
The non-receptor tyrosine phosphatase SHP2 has been at the center of cell signaling research for three decades. SHP2 is required to fully activate the RTK-RAS-ERK cascade, although the underlying mechanisms are not completely understood. , coding for SHP2, is the first identified proto-oncogene that encodes a tyrosine phosphatase, with dominantly activating mutations detected in leukemias and solid tumors.
View Article and Find Full Text PDFBiomacromolecules
February 2025
Traditional polymer systems often rely on toxic initiators or catalysts for cross-linking, posing significant safety risks. For bone tissue engineering, another issue is that the scaffolds often take a longer time to degrade, inconsistent with bone formation pace. Here, we developed an enzyme-responsive biodegradable poly(propylene fumarate) (PPF) and polycaprolactone (PCL) polyphosphoester (PPE) dendrimer cross-linked utilizing click chemistry (EnzDeg-click-PFCLPE scaffold) for enhanced biocompatibility and degradation.
View Article and Find Full Text PDFSenescent osteocytes are key contributors to age-related bone loss and fragility; however, the impact of mechanobiological changes in these cells remains poorly understood. This study provides a novel analysis of these changes in primary osteocytes following irradiation-induced senescence. By integrating subcellular mechanical measurements with gene expression analyses, we identified significant, time-dependent alterations in the mechanical properties of senescent bone cells.
View Article and Find Full Text PDFBone pathologies such as osteoporosis and metastasis can significantly compromise the load-bearing capacity of the spinal column, increasing the risk of vertebral fractures, some of which may occur during routine physical activities. Currently, there is no clinical tool that accurately assesses the risk of vertebral fractures associated with these activities in osteoporotic and metastatic spines. In this paper, we develop and validate a quantitative computed tomography-based finite element analysis (QCT/FEA) method to predict vertebral fractures under general load conditions that simulate flexion, extension, and side-bending movements, reflecting the body's activities under various scenarios.
View Article and Find Full Text PDFBackground: Longevity is increasing worldwide due to improvements in healthcare and living standards. Aging is often associated with disability and multiple health concerns. To address these challenges, effective interventions are essential.
View Article and Find Full Text PDFIntroduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized.
Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.
There is a significant clinical need to develop effective treatments for bone defects in patients with diabetes mellitus (DM), as they are at higher risk of fractures and impaired healing. Guided bone tissue engineering using biocompatible and biodegradable polymers is a promising approach. However, current diabetic bone regenerative therapies often fail due to the accumulation of advanced glycation products, which can affect the integration of traditional tissue engineering scaffolds with native bone.
View Article and Find Full Text PDFPurpose: Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors.
Patients And Methods: The IMbrave150 study's atezo-bev group was analyzed.
Purpose: We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib.
Patients And Methods: Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation.
The growing aging population, with its associated chronic diseases, underscores the urgency for effective tissue regeneration strategies. Biomaterials play a pivotal role in the realm of tissue reconstruction and regeneration, with a distinct shift toward minimally invasive (MI) treatments. This transition, fueled by engineered biomaterials, steers away from invasive surgical procedures to embrace approaches offering reduced trauma, accelerated recovery, and cost-effectiveness.
View Article and Find Full Text PDFDegenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat.
View Article and Find Full Text PDFSegmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one-stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4-week implantation study.
View Article and Find Full Text PDF3D stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as nonspecific differentiation issues due to the complicated environment following transplantation. In this study, functional 3D spheroids are developed using mesenchymal stem cells with 2D hetero-nanostructures (HNSs) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNTs) and gelatin-bind black phosphorus nanosheets (gBPNSs).
View Article and Find Full Text PDFBackground: Autologous bone grafts are currently the standard in orthopedic surgery despite limited donor sources and the prevalence of donor site morbidity. Other alternatives such as allografts are more readily available than autografts but have lower rates of graft incorporation.
Methods: Here, we propose a novel graft alternative consisting of an injectable poly(propylene fumarate) (PPF) and poly(propylene fumarate-co-caprolactone) P(PF--CL) copolymer with a recombinant human bone morphogenetic protein-2 (rhBMP-2)/vascular epithelial growth factor (VEGF) release system accompanied by hydroxyapatite (HA).
Polycaprolactone fumarate (PCLF) is a cross-linkable PCL derivative extensively considered for tissue engineering applications. Although injection molding has been widely used to develop PCLF scaffolds, platforms developed using such technique lack precise control on architecture, design, and porosity required to ensure adequate cellular and tissue responses. In particular, the scaffolds should provide a suitable surface for cell attachment and proliferation, and facilitate cell-cell communication and nutrient flow.
View Article and Find Full Text PDFPre-formed hydrogel scaffolds have emerged as favorable vehicles for tissue regeneration, promoting minimally invasive treatment of native tissue. However, due to the high degree of swelling and inherently poor mechanical properties, development of complex structural hydrogel scaffolds at different dimensional scales has been a continuous challenge. Herein, we take a novel approach at the intersections of engineering design and bio-ink chemistry to develop injectable pre-formed structural hydrogel scaffolds fabricated via visible light (VL) induced digital light processing (DLP).
View Article and Find Full Text PDFThree-dimensional (3D) printing technology is driving forward the progresses of various engineering fields, including tissue engineering. However, the pristine 3D-printed scaffolds usually lack robust functions in stimulating desired activity for varied regeneration applications. In this study, we combined the two-dimensional (2D) hetero-nanostructures and immuno-regulative interleukin-4 (IL-4) cytokines for the functionalization of 3D-printed scaffolds to achieve a pro-healing immuno-microenvironment for optimized bone injury repair.
View Article and Find Full Text PDFJ Infect Dev Ctries
March 2023
Introduction: Poor literacy is associated with hepatitis morbidity and mortality. Adolescents are especially at risk of hepatitis C. This study investigated viral hepatitis literacy, risk, and influencing factors among Chinese middle and high school students.
View Article and Find Full Text PDFCurrent bone cement systems often demand free radical or metal-related initiators and/or catalysts for the crosslinking process, which may cause serious toxicity to the human body. In addition, the resultant dense scaffolds may have a prolonged degradation time and are difficult for cells to infiltrate and form new tissue. In this study, we developed a porous "click" organic-inorganic nanohybrid (PO-click-ON) cement that crosslinks via metal-free biorthogonal click chemistry and forms porous structures mimicking the native bone tissue via particulate leaching.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
May 2023
Background & Aims: Complex communications between hepatocytes and Kupffer cells (KCs) are known to drive or suppress hepatocarcinogenesis, with controversial data in the literature. In previous experiments that aimed to decipher hepatocyte/KC interactions, we unexpectedly unveiled a tumor-suppressing effect of polyinosinic-polycytidylic acid, a widely used inducer of MX dynamin like GTPase 1 (Mx1)-cre expression, which questioned a theory of interleukin 1a/6 cytokine circuit in hepatocyte/KC communication. The goal of this study was to clarify the controversy and decipher unique functions of KCs and non-KC macrophages in liver tumorigenesis.
View Article and Find Full Text PDFFunctional cellular structures with controllable mechanical and morphological properties are of great interest for applications including tissue engineering, energy storage, and aerospace. Additive manufacturing (AM), also referred to as 3D printing, has enabled the potential for fabrication of functional porous scaffolds (i.e.
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