Enhanced Discriminability of Viral Vectors in Viscous Nanopores.

Achieving safe and efficient gene therapy hinges upon the inspection of genomes enclosed within individual nano-carriers to mitigate potential health risks associated with empty or fragment-filled vectors. Here solid-state nanopore sensing is reported for identifications of intermediate adeno-associated virus (AAV) vectors in liquid. The method exploits the phenomenon of translocation slowdown induced by the viscosity of salt water-organic mixtures.

Predicting gene expression state and prioritizing putative enhancers using 5hmC signal.

Background: Like its parent base 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) is a direct epigenetic modification of cytosines in the context of CpG dinucleotides. 5hmC is the most abundant oxidized form of 5mC, generated through the action of TET dioxygenases at gene bodies of actively-transcribed genes and at active or lineage-specific enhancers. Although such enrichments are reported for 5hmC, to date, predictive models of gene expression state or putative regulatory regions for genes using 5hmC have not been developed.

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.

Purpose: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs.

Methods: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs.

Anti-Vα24Jα18 TCR Antibody Tunes iNKT Cell Responses to Target and Kill CD1d-negative Tumors in an FcγRII (CD32)-dependent Manner.

Unlabelled: Invariant natural killer T (iNKT) cells play an essential role in antitumor immunity by exerting cytotoxicity and producing massive amounts of cytokines. iNKT cells express invariant T-cell receptors (TCR) to recognize their cognate glycolipid antigens such as α-galactosylceramide (α-GalCer) presented on CD1d. We recently reported that iNKT cells recognize CD1d-negative leukemia cell line K562 in a TCR-dependent manner.

Long-term treatment outcomes in gastric cancer with oligometastasis.

Aim: While surgery is essential for curative treatment of gastric cancer with oligometastasis, its target, timing, and possibility of combination with other treatments are unclear. We herein investigated the clinical course and long-term outcomes of gastric cancer with oligometastasis in the real world setting to determine the optimal therapeutic strategy.

Methods: The present study retrospectively analyzed 992 patients who received any treatment for metastatic or recurrent gastric adenocarcinoma at Tokyo Metropolitan Komagome Hospital between 2007 and 2019.

Co-option of an Astacin Metalloprotease Is Associated with an Evolutionarily Novel Feeding Morphology in a Predatory Nematode.

Animals consume a wide variety of food sources to adapt to different environments. However, the genetic mechanisms underlying the acquisition of evolutionarily novel feeding morphology remain largely unknown. While the nematode Caenorhabditis elegans feeds on bacteria, the satellite species Pristionchus pacificus exhibits predatory feeding behavior toward other nematodes, which is an evolutionarily novel feeding habit.

The Cellular Accumulation of Vehicle Exhaust Particulates Changes the Acidic pH Environment of Lysosomes in BEAS-2B Airway Epithelial Cells.

Many people are exposed every day to vehicle exhaust particulates (VEPs), which are thought to be taken up by epithelial cells that are the first barrier in our biological defense. The study aim was to investigate how VEPs are processed in the lysosomal degradation system. BEAS-2B airway epithelial cells easily ingest VEPs and have been shown to accumulate in cells for several days, but no elevated cytotoxicity was observed over that time period.

Development of a novel purification method for AAV vectors using tangential flow filtration.

Adeno-associated virus (AAV) vector can efficiently transduce therapeutic genes in various tissue types with less side effects; however, owing to complex multistep processes during manufacture, there have been surges in the pricing of recently approved AAV vector-based gene therapy products. This study aimed to develop a simple and efficient method for high-quality purification of AAV vector via tangential flow filtration (TFF), which is commonly used for concentration and diafiltration of solutions during AAV vector purification. We established a novel purification method using TFF and surfactants.

Robotically assisted total gastrectomy for lymphadenopathy after long-term follow-up for multiple type 1 gastric neuroendocrine tumor (NET): a case report.

Background: Type 1 gastric neuroendrine tumor (NET) is usually associated with chronic atrophic gastritis and forms multiple lesions. While most cases of type 1 gastric NET are generally slowly growing, some develop regional lymph node metastases even after long-term dormancy.

Case Presentation: A 73-year-old male patient with a 32-year history of multiple gastric NET was being followed-up at the study center after endoscopic submucosal dissection (ESD) of a large gastric NET.

Inducible disruption of genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch.

The three mammalian TET dioxygenases oxidize the methyl group of 5-methylcytosine in DNA, and the oxidized methylcytosines are essential intermediates in all known pathways of DNA demethylation. To define the in vivo consequences of complete TET deficiency, we inducibly deleted all three genes in the mouse genome. () mice succumbed to acute myeloid leukemia (AML) by 4 to 5 wk.

Acquired diaphragmatic hernia following a peritoneal biopsy for gastric cancer dissemination in the diaphragm: a case report.

Background: Acute diaphragmatic hernia is a life-threatening condition caused by prolapse of an abdominal organ into the thoracic cavity through a defect in the diaphragm. We present herein a case of acquired diaphragmatic hernia following a peritoneal biopsy for gastric cancer dissemination in the diaphragm.

Case Presentation: A 72-year-old, female patient presented with a complaint of acute abdomen 10 months after receiving a diagnosis of stage IV gastric cancer with peritoneal dissemination based on peritoneal biopsy findings during staging laparoscopy.

CD69 Imposes Tumor-Specific CD8+ T-cell Fate in Tumor-Draining Lymph Nodes.

Tumor-specific CD8+ T cells play a pivotal role in antitumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stemlike CD8+ T cells give rise to their cytotoxic progeny-Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated.

Pathogenic helper T cells as the novel therapeutic targets for immune-mediated intractable diseases.

Allergic diseases arise from a complex interplay between immune system and environmental factors. A link between the pathogenesis of allergic diseases and type 2 immune responses has become evident, with conventional and pathogenic type 2 helper T (Th2) cells involved in both. Recently, there has been a significant development in therapeutic agents for allergic diseases: IL-5 and IL-5 receptor antagonists, Janus kinase (JAK) inhibitors, and sublingual immunotherapy (SLIT).

Robotic distal gastrectomy with D2 lymphadenectomy for advanced gastric cancer with celiac-arterial anomaly (Adachi type VI, group 26): Case report.

In gastric cancer surgery, some celiac-arterial anomalies are associated with a risk of anatomical misidentification and insufficient lymphadenectomy. We herein report a case of successful robotic distal gastrectomy with D2 lymphadenectomy based on preoperative, anatomical recognition using three-dimensional computed tomography (3D-CT) in a patient with advanced gastric cancer and a rare anomaly of the celiac artery. A 64-year-old, male patient was referred to our division with a diagnosis of advanced gastric cancer.

Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism.

CD4 memory T cells are central to long-lasting protective immunity and are involved in shaping the pathophysiology of chronic inflammation. While metabolic reprogramming is critical for the generation of memory T cells, the mechanisms controlling the redox metabolism in memory T cell formation remain unclear. We found that reactive oxygen species (ROS) metabolism changed dramatically in T helper-2 (Th2) cells during the contraction phase in the process of memory T cell formation.

Liver group 2 innate lymphoid cells regulate blood glucose levels through IL-13 signaling and suppression of gluconeogenesis.

The liver stores glycogen and releases glucose into the blood upon increased energy demand. Group 2 innate lymphoid cells (ILC2) in adipose and pancreatic tissues are known for their involvement in glucose homeostasis, but the metabolic contribution of liver ILC2s has not been studied in detail. Here we show that liver ILC2s are directly involved in the regulation of blood glucose levels.

The Clinical Impact of Synchronous and Metachronous Other Primary Cancer in Gastric Cancer Patients Who Receive Curative Treatment.

Background/aim: The present study evaluated the clinical characteristics and prognostic factors of gastric cancer (GC) patients with synchronous and metachronous other primary cancer who received curative treatment for GC.

Patients And Methods: The study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified.

Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis.

Type 2 helper T (Th2) cells, a subset of CD4 T cells, play an important role in the host defense against pathogens and allergens by producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, to trigger inflammatory responses. Emerging evidence reveals that Th2 cells also contribute to the repair of injured tissues after inflammatory reactions. However, when the tissue repair process becomes chronic, excessive, or uncontrolled, pathological fibrosis is induced, leading to organ failure and death.

The Albumin-Bilirubin Score Is a Prognostic Factor for Gastric Cancer Patients Who Receive Curative Treatment.

Background/aim: The albumin-bilirubin (ALBI) score is a promising tool for the evaluation of the perioperative hepatic function. The present study aimed to evaluate the clinical impact of the preoperative ALBI status in patients with gastric cancer (GC) who received curative treatment.

Patients And Methods: The present study included 244 patients who underwent curative treatment for GC between 2005 and 2018.

The Platelet-to-Lymphocyte Ratio Is an Independent Prognostic Factor for Patients With Esophageal Cancer Who Receive Curative Treatment.

Background: Perioperative systemic inflammation affects the long-term oncological outcomes of patients with malignancies. We evaluated the clinical impact of the preoperative platelet-to-lymphocyte ratio (PLR) in patients with resectable esophageal cancer who received curative treatment.

Patients And Methods: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018.

Clinical Impact of Platelet-to-albumin Ratio on Esophageal Cancer Patients Who Receive Curative Treatment.

Background/aim: Perioperative nutrition and inflammation affect the oncological outcomes of various malignancies. We evaluated the clinical impact of the preoperative platelet-to-albumin ratio (PAR) in resectable esophageal cancer patients who received curative treatment.

Patients And Methods: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018.

Selective Growth Suppressive Effect of Pravastatin on Senescent Human Lung Fibroblasts.

Various chemical reagents containing inhibitors of mitochondrial activity, antioxidants, nuclear factor-kappa B (NF-kB) inhibitor, mammalian target of rapamycin (mTOR) inhibitor and other clinical therapeutics were screened in order to identify those that selectively decrease the viability of senescent human lung fibroblasts. Cell viability was measured using the CCK-8 assay. The results showed that pravastatin, a drug for hyperlipidemia, decreased the viability of senescent cells but not non-senescent cells.

A Case of Robotic Posterior Rectopexy for Full-thickness Rectal Prolapse.

We describe our experience with robotic posterior rectopexy for a patient with full-thickness rectal prolapse. To our knowledge, this is the first report of such a case in the literature. A 94-year-old woman presented with a history of gradually worsening rectal prolapse.