Objective: Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study.
Methods: Patients with synchronous or metachronous LMGC received 2-4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection.
Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets.
View Article and Find Full Text PDFBackground: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted.
View Article and Find Full Text PDFMesenchymal stem cells (MSCs) have potential as a viable treatment option in the field of regenerative medicine, but MSC-based therapy needs to be more efficient. Preconditioning is a method to improve MSC-based therapy, and dimethyl fumarate (DMF) - an agent that can enhance the antioxidative capacity of cells - can be considered for preconditioning of MSCs. In this study, we treated bone marrow-derived MSCs with DMF and evaluated their proteome using bottom-up proteomics.
View Article and Find Full Text PDFVon Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target.
View Article and Find Full Text PDFCommensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes.
View Article and Find Full Text PDFIn the study of degenerative brain diseases, changes in lipids, the main component of neurons, are particularly important because they are used as indicators of pathological changes. One method for the sensitive measurement of biomolecules, especially lipids, is time-of-flight secondary ion mass spectrometry (ToF-SIMS) using pulsed argon cluster ions. In this study, biomolecules including various lipids present in normal mouse brain tissue were measured using ToF-SIMS equipped with pulsed argon cluster primary ions.
View Article and Find Full Text PDFPhytochrome B (phyB) is a plant photoreceptor that forms a membraneless organelle called a photobody. However, its constituents are not fully known. Here, we isolated phyB photobodies from Arabidopsis leaves using fluorescence-activated particle sorting and analyzed their components.
View Article and Find Full Text PDFThe loss of endothelial cells is associated with the accumulation of monocytes/macrophages underneath the surface of the arteries, where cells are prone to mechanical stimulation, such as shear stress. However, the impact of mechanical stimuli on monocytic cells remains unclear. To assess whether mechanical stress affects monocytic cell function, we examined the expression of inflammatory molecules and surface proteins, whose levels changed following shear stress in human THP-1 cells.
View Article and Find Full Text PDFFibroblast growth factor 21 (FGF21) has pharmaceutical potential against obesity-related metabolic disorders, including non-alcoholic fatty liver disease. Since thermal stability is a desirable factor for therapeutic proteins, we investigated the thermal behavior of human FGF21. FGF21 remained soluble after heating; thus, we examined its temperature-induced structural changes using circular dichroism (CD).
View Article and Find Full Text PDFObjective: To evaluate whether metaphase I (MI) oocytes completing maturation in vitro to metaphase II ("MI-MII oocytes") have similar developmental competence as the sibling metaphase II (MII) oocytes that reached maturity in vivo.
Design: Retrospective cohort study.
Setting: Academic medical center.
Aims: The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs.
View Article and Find Full Text PDFInhibitors of apoptosis proteins (IAPs), defined by the presence of baculovirus IAP repeat (BIR) protein domain, are critical regulators of cell survival and cell death processes. Cellular IAP 1/2 (cIAP1/2) and X-linked IAPs (XIAPs) regulate the innate immune signaling pathway through their E3 ubiquitin ligase activity. Peptidomimetics or small-molecule IAP antagonists have been developed to treat various diseases, such as cancer, infection, and inflammation.
View Article and Find Full Text PDFThe AKT signaling pathway plays critical roles in the resolution of inflammation. However, the underlying mechanisms of anti-inflammatory regulation and signal coordination remain unclear. Here, we report that anti-inflammatory AKT signaling is coordinated by glutamyl-prolyl-tRNA synthetase 1 (EPRS1).
View Article and Find Full Text PDFGastric cancer (GC) is the most common cancer worldwide and the third leading cause of cancer death, with the fifth highest incidence. The development of effective chemotherapeutic agents is needed to decrease GC mortality. Policosanol (PC) extracted from Cuban sugar cane wax is a healthy functional food ingredient that helps improve blood cholesterol levels and blood pressure.
View Article and Find Full Text PDFThe host immune system possesses an intrinsic ability to target and kill cancer cells in a specific and adaptable manner that can be further enhanced by cancer immunotherapy, which aims to train the immune system to boost the antitumor immune response. Several different categories of cancer immunotherapy have emerged as new standard cancer therapies in the clinic, including cancer vaccines, immune checkpoint inhibitors, adoptive T cell therapy, and oncolytic virus therapy. Despite the remarkable survival benefit for a subset of patients, the low response rate and immunotoxicity remain the major challenges for current cancer immunotherapy.
View Article and Find Full Text PDFPancreatic cancer (PC) has a high mortality rate due to its poor prognosis and the possibility of surgical resection in patients with the disease. Importantly, adjuvant chemotherapy is necessary to improve PC prognosis. Chrysin, a natural product with anti-inflammatory, antioxidant, and anticancer properties, has been studied for several years.
View Article and Find Full Text PDFBackground: The optimal treatment for liver metastasis from gastric cancer (LMGC) remains uncertain. The relevance of surgical resection is controversial. We conducted a prospective multicenter interventional study of surgical resection for LMGC.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is a degenerative disease caused by motor neuron damage in the central nervous system, and it is difficult to diagnose early. is widely used to investigate disease mechanisms and discover biomarkers because it is easy to induce disease in through genetic engineering. We performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to investigate changes in phospholipid distribution in the brain tissue of an ALS-induced model.
View Article and Find Full Text PDFSilica nanoparticles (SiO NPs) are commonly used in medical and pharmaceutical fields. Research into the cytotoxicity and overall proteomic changes occurring during initial exposure to SiO NPs is limited. We investigated the mechanism of toxicity in human liver cells according to exposure time [0, 4, 10, and 16 h (h)] to SiO NPs through proteomic analysis using mass spectrometry.
View Article and Find Full Text PDFBackground: Long-term outcomes of single-incision laparoscopic colectomy (SILC) for colon cancer (CC), as practiced in real-world settings, especially in relation to disease stage, have not been established. We examined, retrospectively, both short- and long-term outcomes of SILC versus those of multiport laparoscopic colectomy (MPLC) performed for CC in a propensity-score-matched cohort.
Methods: The study involved 263 patient pairs matched 1:1 from among 691 patients who, between January 2008 and May 2014, underwent either SILC or MPLC for a primary solitary CC at our hospital.
Objectives: Sjögren's syndrome (SS) is an autoimmune disease caused by inflammation of the exocrine gland. The pathological hallmark of SS is the infiltration of lymphocytes into the salivary glands. Increased infiltration of T and B cells into salivary glands exacerbates symptoms of SS.
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