Antibody-mimetic drug conjugate with efficient internalization activity using anti-HER2 VHH and duocarmycin.

Antibody-mimetic drug conjugate (AMDC) is a cancer cell-targeted drug delivery system based on the non-covalent binding of mutated streptavidin and modified biotin, namely Cupid and Psyche. However, the development of AMDCs is hampered by difficulties in post-translational modification or poor internalization activity. Here, we report an expression, refolding, and purification method for AMDC using a variable heavy chain of heavy chain-only antibodies (VHHs).

The analysis of fecal calprotectin as a diagnostic marker for anastomotic leakage after rectal cancer surgery: a pilot study.

A prospective pilot study was conducted on 11 patients with rectal cancer to investigate fecal calprotectin (FC) as a diagnostic tool for detecting anastomotic leakage (AL) after low anterior resection. Among the 11 patients, 1 patient (9.1%) experienced AL (Clavien-Dindo Grade IIIa).

Blood vessel remodeling in the cerebral cortex induced by binge alcohol intake in mice.

Unlabelled: Ethanol is toxic to the brain and causes various neurological disorders. Although ethanol can directly exert toxicity on neurons, it also acts on other cell types in the central nervous system. Blood vessel endothelial cells interact with, and are affected by blood ethanol.

Clinical evaluation of a surgical difficulty score for laparoscopic cholecystectomy for acute cholecystitis proposed in the Tokyo Guidelines 2018.

Background/purpose: We evaluated the difficulty score of laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) proposed in the Tokyo guidelines 2018 (TG18) and analyzed the most appropriate scoring method.

Methods: We reviewed 127 patients who underwent LC for AC from January 2018 to March 2022. According to TG18, surgical difficulty was scored for five categories consisting of 25 intraoperative findings.

Intussusception of the cecum due to the acute appendicitis: A case report.

Introduction And Importance: Intussusception of the cecum due to acute appendicitis is rare condition.

Presentation Of Case: A 17-year-old male patient presented to our hospital with a chief complaint of right lower abdominal pain, which had lasted for two days. Computed tomography (CT) revealed a "target sign" from the cecum to the ascending colon, leading to a diagnosis of cecocolic intussusception.

MYPT1-PP1β phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis.

Protein kinase A promotes beige adipogenesis downstream from β-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1β (MYPT1-PP1β) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis.

Pathological complete remission of relapsed tumor by photo-activating antibody-mimetic drug conjugate treatment.

Antibody-mimetic drug conjugate is a novel noncovalent conjugate consisting of an antibody-mimetic recognizing a target molecule on the cancer cell surface and low-molecular-weight payloads that kill the cancer cells. In this study, the efficacy of a photo-activating antibody-mimetic drug conjugate targeting HER2-expressing tumors was evaluated in mice, by using the affibody that recognize HER2 (Z ) as a target molecule and an axially substituted silicon phthalocyanine (a novel potent photo-activating compound) as a payload. The first treatment with the photo-activating antibody-mimetic drug conjugates reduced the size of all HER2-expressing KPL-4 xenograft tumors macroscopically.

Risk factors of incisional hernia at the umbilical specimen extraction site in patients with laparoscopic colorectal cancer surgery.

Purpose: Incisional hernia (IH) is a frequent complication following laparoscopic colorectal surgery. The present study investigated the risk factors for IH after laparoscopic surgery for colorectal cancer.

Methods: A retrospective study was conducted on 202 patients who underwent laparoscopic surgery for colorectal cancer.

The serological diversity of serum IgG/IgA/IgM against SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan.

Background: We compared the temporal changes of immunoglobulin M (IgM), IgG, and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (N), spike 1 subunit (S1), and receptor-binding domain (RBD), and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) to understand the humoral immunity in COVID-19 patients for developing drugs and vaccines for COVID-19.

Methods: A total of five confirmed COVID-19 cases in Nissan Tamagawa Hospital in early August 2020 were recruited in this study. Using a fully automated chemiluminescence immunoassay analyzer, we measured the levels of IgG, IgA, and IgM against SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2 in COVID-19 patients' sera acquired multiple times in individuals from 0 to 76 days after symptom onset.

The Clinical Impact of Apical Lymph Node Metastasis of Colorectal Cancer After Curative Resection.

Purpose: The present study aimed to investigate the clinical implications of apical lymph node metastasis (ALNM) after curative resection of stage III colorectal cancer.

Methods: A retrospective study was conducted of 1403 consecutive colorectal cancer patients who underwent surgical resection at a single institution between April 2008 and January 2020. The characteristics of ALNM, the recurrence status and the relapse-free survival (RFS) were examined.

Comprehensive genomics in androgen receptor-dependent castration-resistant prostate cancer identifies an adaptation pathway mediated by opioid receptor kappa 1.

Castration resistance is a lethal form of treatment failure of prostate cancer (PCa) and is associated with ligand-independent activation of the androgen receptor (AR). It is only partially understood how the AR mediates survival and castration-resistant growth of PCa upon androgen deprivation. We investigated integrative genomics using a patient-derived xenograft model recapitulating acquired, AR-dependent castration-resistant PCa (CRPC).

Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis.

Ballooning degeneration of hepatocytes is a major distinguishing histological feature of non-alcoholic steatosis (NASH) progression that can lead to cirrhosis and hepatocellular carcinoma (HCC). In this study, we evaluated the effect of the selective PPARα modulator (SPPARMα) pemafibrate (Pema) and sodium-glucose cotransporter 2 (SGLT2) inhibitor tofogliflozin (Tofo) combination treatment on pathological progression in the liver of a mouse model of NASH (STAM) at two time points (onset of NASH progression and HCC survival). At both time points, the Pema and Tofo combination treatment significantly alleviated hyperglycemia and hypertriglyceridemia.

Spatiotemporal dynamics of SETD5-containing NCoR-HDAC3 complex determines enhancer activation for adipogenesis.

Enhancer activation is essential for cell-type specific gene expression during cellular differentiation, however, how enhancers transition from a hypoacetylated "primed" state to a hyperacetylated-active state is incompletely understood. Here, we show SET domain-containing 5 (SETD5) forms a complex with NCoR-HDAC3 co-repressor that prevents histone acetylation of enhancers for two master adipogenic regulatory genes Cebpa and Pparg early during adipogenesis. The loss of SETD5 from the complex is followed by enhancer hyperacetylation.

Immunohistochemical detection of hepatocyte nuclear factor-4α in vertebrates.

Hepatocyte nuclear factor-4α (HNF4α) presents in multiple isoforms generated using alternative promoter (P1 and P2) and splicing. Neither conservation of tissue distribution of HNF4α isoforms, nor presence of alternative promoter usage is known. In this study, to detect the expression of HNF4α in some species of animals, we have applied monoclonal antibodies against P1 (K9218) and P2 (H6939) promoter-driven and P1/P2 promoter-driven H1415 HNF4α for immunohistochemistry and western blot analysis.

The risk factors of acute urinary retention after laparoscopic colorectal cancer surgery in elderly patients receiving epidural analgesia.

Purpose: Urinary retention (UR) is a frequent complication following laparoscopic colorectal surgery. The aim of the present study was to investigate the risk factors for acute UR after laparoscopic surgery for colorectal cancer in patients receiving epidural analgesia.

Methods: A retrospective study was conducted of 201 patients who underwent laparoscopic surgery for colorectal cancer among those receiving epidural analgesia.

Loss of Down syndrome critical region-1 leads to cholesterol metabolic dysfunction that exaggerates hypercholesterolemia in ApoE-null background.

Down syndrome critical region (DSCR)-1 functions as a feedback modulator for calcineurin-nuclear factor for activated T cell (NFAT) signals, which are crucial for cell proliferation and inflammation. Stable expression of DSCR-1 inhibits pathological angiogenesis and septic inflammation. DSCR-1 also plays a critical role in vascular wall remodeling associated with aneurysm development that occurs primarily in smooth muscle cells.

A clinical risk analysis of early post-operative delirium after laparoscopic colorectal cancer surgery in elderly patients: a retrospective study.

Purpose: Early post-operative delirium (EPOD) is a frequent complication following colorectal surgery. The present study investigated the risk factors for EPOD after laparoscopic colorectal surgery in elderly patients.

Methods: A retrospective study was conducted among 208 patients ≥70 years old who underwent laparoscopic colorectal surgery.

Colon perforation caused by transanal decompression tube after laparoscopic low anterior resection: A case report.

Introduction: The effectiveness of transanal decompression tube (TDT) to prevent anastomotic leakage after rectal surgery has been widely accepted in recent years. However, a rare complication of intestinal perforation due to TDT has been also reported.

Presentation Of Case: A 88-year-old woman underwent laparoscopic low anterior resection for rectal cancer.

A case of idiopathic myointimal hyperplasia of the mesenteric veins presenting with small bowel obstruction.

Background: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare ischemic bowel disease with venous occlusion resulting from the proliferation of smooth muscles in the venous intima. In most patients, the disease affects rectosigmoid colon and causes persistent abdominal pain and hematochezia, which is similar to inflammatory bowel disease (IBD). In addition, it is difficult to make a precise diagnosis of IMHMV without surgery.

Suppression of liver transplant rejection by anti-donor MHC antibodies via depletion of donor immunogenic dendritic cells.

Background: We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, a tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC (MHCI) antigen (DST-antibodies).

Methods: We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model.

Short-term outcomes of preoperative chemoradiotherapy with S-1 for locally advanced rectal cancer.

The purpose of the present study was to evaluate the short-term results of preoperative chemoradiation therapy with S-1 for locally advanced rectal cancer. A total of 32 patients with advanced rectal cancer who had been treated with preoperative chemoradiotherapy with S-1 and underwent surgical resection between May 2012 and December 2019 were analyzed. Advanced rectal cancer of clinical stage II and III was diagnosed in 13 (41%) and 19 (59%) patients, respectively.

The treatment for refractory rectovaginal fistula after low anterior resection with estriol, polyglycolic acid sheets and primary closure: A case report.

Introduction: Rectovaginal fistula (RVF) is a refractory complication that occurs after anastomotic leakage following low anterior resection for rectal disease. Due to its refractory nature, RVF is often managed with surgical treatment, such as stoma creation for fecal diversion, closure of the fistula and/or re-anastomosis, rather than conservative therapy.

Presentation Of Case: A 72-year-old woman who underwent laparoscopic low anterior resection developed RVF on post-operative day (POD) 15.