Hydroxyurea inhibits proliferation and stimulates apoptosis through inducible nitric oxide synthase in erythroid cells.

Hydroxyurea (hydroxycarbamide, HU) arrests cells in the S-phase by inhibiting ribonucleotide reductase and DNA synthesis, significantly contributing to the release of nitric oxide (NO). We investigated the involvement of inducible NO synthase (NOS2) in the cytostatic effect of HU using in vitro shRNA-induced knockdown of the NOS2 transcript (NOS2) or a specific NOS2 inhibitor (1400W) in human erythroleukemic HEL92.1.

Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis.

Erythropoietin (EPO) plays a key role in energy metabolism, with EPO receptor (EpoR) expression in white adipose tissue (WAT) mediating its metabolic activity. Here, we show that male mice lacking EpoR in adipose tissue exhibit increased fat mass and susceptibility to diet-induced obesity. Our findings indicate that EpoR is present in WAT, brown adipose tissue, and skeletal muscle.

High nitrate levels in skeletal muscle contribute to nitric oxide generation via a nitrate/nitrite reductive pathway in mice that lack the nNOS enzyme.

Introduction: Nitric oxide (NO) is a vasodilator gas that plays a critical role in mitochondrial respiration and skeletal muscle function. NO is endogenously generated by NO synthases: neuronal NO synthase (nNOS), endothelial NO synthase (eNOS), or inducible NO synthase (iNOS). NO in skeletal muscle is partly generated by nNOS, and nNOS deficiency can contribute to muscular dystrophic diseases.

Neuronal nitric oxide synthase required for erythropoietin modulation of heart function in mice.

Erythropoietin (EPO) acts primarily in regulating red blood cell production mediated by high EPO receptor (EPOR) expression in erythroid progenitor cells. EPO activity in non-erythroid tissue is evident in mice with EPOR restricted to erythroid tissues (ΔEPORE) that become obese, glucose-intolerant, and insulin-resistant. In animal models, nitric oxide synthase (NOS) contributes to EPO activities including erythropoiesis, neuroprotection, and cardioprotection against ischemia-reperfusion injury.

Efficacy and safety of ivermectin in patients with mild COVID-19 in Japan and Thailand.

Background: Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option.

Methods: This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study).

The p53 DNA damage response and Fanconi anemia DNA repair pathway protect against acetaldehyde-induced replication stress in esophageal keratinocytes.

Alcohol contributes to cellular accumulation of acetaldehyde, a primary metabolite of alcohol and a major human carcinogen. Acetaldehyde can form DNA adducts and induce interstrand crosslinks (ICLs) that are repaired by the Fanconi anemia DNA repair pathway (FA pathway). Individuals with deficiency in acetaldehyde detoxification or in the FA pathway have an increased risk of squamous-cell carcinomas (SCCs) including those of the esophagus.

Neuronal nitric oxide synthase is required for erythropoietin stimulated erythropoiesis in mice.

Erythropoietin (EPO), produced in the kidney in a hypoxia responsive manner, is required for red blood cell production. In non-erythroid tissue, EPO increases endothelial cell production of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) that regulates vascular tone to improve oxygen delivery. This contributes to EPO cardioprotective activity in mouse models.

Koshidacins A and B, Antiplasmodial Cyclic Tetrapeptides from the Okinawan Fungus FKR-0564.

Two new antiplasmodial peptides, named koshidacins A () and B (), were discovered from the culture broth of the Okinawan fungus FKR-0564. Their structures, including absolute configurations, were elucidated by a combination of spectroscopic methods and chemical derivatization. Both compounds showed moderate antiplasmodial activity against strains, with IC values ranging from 17.

[Biphasic Pulmonary Blastoma without Recurrence for Six Years After Surgery:Report of a Case].

A 62-year-old man was referred to our hospital for a lung tumor. Computed tomography (CT) of the chest showed a 62×55×68 mm well-circumscribed tumor in the upper lobe of the right lung. A transbronchial lung biopsy was performed, but a diagnosis was not achieved.

Erythropoietin Non-hematopoietic Tissue Response and Regulation of Metabolism During Diet Induced Obesity.

Erythropoietin (EPO) receptor (EPOR) determines EPO response. High level EPOR on erythroid progenitor cells gives rise to EPO regulated production of red blood cells. Animal models provide evidence for EPO activity in non-hematopoietic tissue mediated by EPOR expression.

FANCD2 limits acetaldehyde-induced genomic instability during DNA replication in esophageal keratinocytes.

Individuals with Fanconi anemia (FA), a rare genetic bone marrow failure syndrome, have an increased risk of young-onset head and neck squamous cell carcinomas (SCCs) and esophageal SCC. The FA DNA repair pathway is activated upon DNA damage induced by acetaldehyde, a chief alcohol metabolite and one of the major carcinogens in humans. However, the molecular basis of acetaldehyde-induced genomic instability in SCCs of the head and neck and of the esophagus in FA remains elusive.

Incidence of and risk factors for hip fracture in Nagasaki, Japan from 2005 to 2014.

Unlabelled: The annual incidence of new hip fractures increased from 2005 to 2014 in Nagasaki and females were much more affected. High-risk factors were identified as age ≥ 80 years, winter, indoors, living room, Monday, and early morning. Seven days after admission, most patients remained hospitalized and had been treated surgically.

Erythropoietin treatment and the risk of hip fractures in hemodialysis patients.

Erythropoietin (EPO) is the primary regulator of bone marrow erythropoiesis. Mouse models have provided evidence that EPO also promotes bone remodeling and that EPO-stimulated erythropoiesis is accompanied by bone loss independent of increased red blood cell production. EPO has been used clinically for three decades to treat anemia in end-stage renal disease, and notably, although the incidence of hip fractures decreased in the United States generally after 1990, it rose among hemodialysis patients coincident with the introduction and subsequent dose escalation of EPO treatment.

Maf1 limits RNA polymerase III-directed transcription to preserve genomic integrity and extend lifespan.

A key to longevity assurance is the nutrient-sensing mTOR pathway. Inhibition of mTOR extends lifespan in a variety of organisms. However, the downstream effectors of the mTOR pathway for lifespan regulation are elusive.

Rectal varix treated with endoscopic cyanoacrylate injection therapy.

There is no established treatment for rectal varices. Although endoscopic cyanoacrylate (N-butyl 2-cyanoacrylate) injection therapy is the standard treatment for gastric varices, there are few reports of its use for rectal varices. We present a case of rectal varix that was successfully treated with endoscopic cyanoacrylate injection therapy.

Effects of Erythropoietin in White Adipose Tissue and Bone Microenvironment.

Erythropoietin (EPO) is expressed primarily in fetal liver and adult kidney to stimulate red blood cell production. Erythropoietin receptor expression is not restricted to erythroid progenitor cells, and non-erythroid EPO activity includes immune response and bone remodeling. In bone fracture models, EPO administration promotes bone formation and accelerates bone healing.

Erythropoietin reduces fat mass in female mice lacking estrogen receptor alpha.

Objective: Erythropoietin (EPO), the cytokine required for erythropoiesis, contributes to metabolic regulation of fat mass and glycemic control. EPO treatment in mice on high-fat diets (HFD) improved glucose tolerance and decreased body weight gain via reduced fat mass in males and ovariectomized females. The decreased fat accumulation with EPO treatment during HFD in ovariectomized females was abrogated with estradiol supplementation, providing evidence for estrogen-related gender-specific EPO action in metabolic regulation.

Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

Objective: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results.

Design: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours.

Erythropoietin regulates metabolic response in mice via receptor expression in adipose tissue, brain, and bone.

Erythropoietin (EPO) acts by binding to erythroid progenitor cells to regulate red blood cell production. While EPO receptor (Epor) expression is highest on erythroid tissue, animal models exhibit EPO activity in nonhematopoietic tissues, mediated, in part, by tissue-specific Epor expression. This review describes the metabolic response in mice to endogenous EPO and EPO treatment associated with glucose metabolism, fat mass accumulation, and inflammation in white adipose tissue and brain during diet-induced obesity and with bone marrow fat and bone remodeling.

Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction with surgically altered anatomy: a multicenter prospective registration study.

Background: Endoscopic treatment for malignant biliary obstruction (MBO) in patients bearing surgically altered anatomy (SAA) is not well-established. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a new treatment option for MBO, limited data are available regarding the efficacy and safety of EUS-BD in patients with SAA. We conducted a multicenter prospective registration study to evaluate the efficacy and safety of EUS-BD in this population.

Airborne particle dispersion around the feet of surgical staff while walking in and out of a bio-clean operating theatre.

Background: Bacterial contamination by airborne particles is one of the most important factors in the pathogenesis of surgical-site infections.

Aim: This study aimed to identify the generation and behaviour of airborne particles around the feet of surgical staff while walking in and out of an operating theatre.

Methods: Two physicians and two nurses walked in and out of a bio-clean theatre under laminar airflow, either individually or as a group.

Erythropoietin signaling in osteoblasts is required for normal bone formation and for bone loss during erythropoietin-stimulated erythropoiesis.

Erythropoietin (EPO) regulates erythropoiesis by binding to erythropoietin receptor (Epor) on erythroid progenitor cells. Epor is also expressed on bone forming osteoblasts and bone loss accompanies EPO-stimulated erythropoiesis in mice. Mice with Epor restricted to erythroid tissue exhibit reduced bone and increased marrow adipocytes; in contrast, transgenic mice (Tg) with osteoblastic-specific deletion of Epor exhibit reduced trabecular bone with age without change in marrow adipocytes.