Total Synthesis of a TNBC-Selective Cytotoxic Bromo Nor-eremophilane, PC-A, and Its Preliminary Structure-Activity Relationships.

PC-A (), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure-activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of was achieved starting from ()-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction.

Continuous Deep Sedation for Psycho-Existential Suffering: A Multicenter Nationwide Study.

There is ongoing debate on whether continuous deep sedation (CDS) for psycho-existential suffering is appropriate. We aimed to (1) clarify clinical practice of CDS for psycho-existential suffering and (2) assess its impact on patients' survival. Advanced cancer patients admitted to 23 palliative care units in 2017 were consecutively enrolled.

Cross-cultural comparison of continuous deep sedation for advanced cancer patients in East Asian countries: prospective cohort study.

Objective: Cultural, social, and legal factors have been known to affect physicians' practice of continuous deep sedation. There have been few quantitative studies to compare continuous deep sedation practice in Asian countries. We aimed to describe and compare clinical characteristics of continuous deep sedation in Japan, Korea and Taiwan.

Bicyclic Chalcones as Mitotic Inhibitors for Overcoming Androgen Receptor-Independent and Multidrug-Resistant Prostate Cancer.

To improve the biological effects of the lead compound 5'-chloro-2,2'-dihydroxychalcone (Cl-DHC), bicyclic aromatic chalcones were designed, synthesized, and evaluated against androgen-independent prostate cancer (PCa) DU145 and PC-3 cell proliferation. Newly synthesized bi-naphthyl derivatives and suppressed the proliferation of these two cell lines and also taxane-resistant prostate cancer cell lines at a submicromolar level. The two compounds were 4-18 times more potent than the parent molecule Cl-DHC.

Continuous deep sedation at the end of life in children with cancer: experience at a single center in Japan.

Continuous deep sedation (CDS) is used to alleviate unbearable and otherwise refractory symptoms in patients dying of cancer. No data are available concerning CDS in children from Japan to date. This study primarily aimed to describe experience in CDS in child cancer patients at Kyoto University Hospital.

Proton pump inhibitor use increases the risk of peritonitis in peritoneal dialysis patients.

Peritonitis is a major and the most significant complication of peritoneal dialysis (PD). Although some predictors of peritonitis in PD patients are known, the association between proton pump inhibitor (PPI) use and peritonitis has not been characterized. Here, we examined whether PPI use is a risk factor for the development of peritonitis, based on a single-center retrospective analysis of 230 consecutive Japanese PD patients at Narita Memorial Hospital.

Changes in opinions on palliative sedation of palliative care specialists over 16 years and their effects on clinical practice.

Purposes: Despite extensive debate on palliative sedation over the last few decades, no studies have explored longitudinal changes in physicians' opinion. Moreover, little is known about how physicians' opinions affect their practice. This study aimed to clarify (1) changes in palliative care specialists' opinions on palliative sedation and (2) the effects of these opinions on clinical practice.

Japanese physicians' experiences of terminally ill patients voluntarily stopping eating and drinking: a national survey.

Objectives: Voluntarily stopping eating and drinking (VSED) could be regarded as a patients' own non-treatment decision that hastens death, which involves patients voluntarily forgoing food and liquid until death. The aims of this study were to investigate the experience of home hospice physicians and palliative care specialists who care for patients during VSED in Japan, and their opinions on continuous deep sedation (CDS) as a means to relieve patient symptoms during VSED.

Methods: 219 home hospice physicians and 695 palliative care specialists across Japan were surveyed by mail questionnaire in 2016.

Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice.

Parental behavior in mammals is innate, but it is also facilitated by social experience, specifically social interactions between the parent and infant. Social interactions with infants also induce the alloparental behavior of virgin animals. Oxytocin (OT) plays an important role in mediating alloparental behavior.

[Development of CMV retinitis in an antigenemia-negative infant after cord blood transplantation].

A five-month-old male infant with familial hemophagocytic lymphohistiocytosis underwent cord blood transplantation using reduced-intensity conditioning. Methylprednisolone (mPSL) pulse administration was performed for marked pulmonary edema during the early phase of transplantation, followed by GVHD treatment with mPSL until day 100. CMV antigenemia was detected on days 27 and 55, but serum became negative with 2- to 3-week ganciclovir (GCV) treatment on both occasions.

Acute lymphoblastic leukemia in a girl with Wilson's disease.

Wilson's disease (WD) is an autosomal recessive defect in cellular copper transportation. Although acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy, only two cases of ALL associated with WD have been reported to date. One patient died of relapse and infection, and the other died of neutropenic sepsis during the treatment.

Munc13-4 deficiency with CD5 downregulation on activated CD8+ T cells.

Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by uncontrolled activation of T cells and macrophages and hypercytokinemia. We have recently described a significant increase in a subpopulation of CD8(+) T cells with downregulation of CD5 during the acute phase of FHL type2 (FHL2; perforin deficiency), which declines after successful treatment, with a concomitant reduction in serum cytokine level. This unusual subset of CD8(+) T cells, however, has not been characterized in patients with other subtypes of FHL.

Sulforaphane inhibits advanced glycation end product-induced pericyte damage by reducing expression of receptor for advanced glycation end products.

Advanced glycation end products (AGEs) not only inhibit DNA synthesis but also play a role in diabetic retinopathy by evoking apoptosis and inflammation in retinal pericytes via interaction with a receptor for AGE (RAGE). Similarly, sulforaphane, which is a naturally occurring isothiocyanate that is found in widely consumed cruciferous vegetables, protects against oxidative stress-induced tissue damage. Therefore, we hypothesized that sulforaphane could inhibit AGE-induced pericytes injury through its antioxidative properties.

An endobronchial inflammatory myofibroblastic tumor in a 10-yr-old child after allogeneic hematopoietic cell transplantation.

IMTs belong to the group of soft tissue tumor and could occur at any anatomical site; however, the causes and growth feature remain unclear. This case report documents a 10-yr-old male suffering from slowly developing dyspnea on exertion and cough around seven months post-HCT. He was diagnosed with an endobronchial tumor based on imaging, and histology confirmed ALK-positive submucosal spindle-shaped cells with infiltrative cells, compatible with IMT.

Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

Background: Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established.

Methods: Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.

Pigment epithelium-derived factor improves metabolic derangements and ameliorates dysregulation of adipocytokines in obese type 2 diabetic rats.

Oxidative stress and inflammation in the adipose tissues contribute to the metabolic syndrome. Pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, it remains unclear whether PEDF could suppress adipocyte inflammation.

Fat embolism syndrome: an autopsy-proven case involving a patient on dialysis and systemic scleroderma.

A 66-year-old woman receiving continuous ambulatory peritoneal dialysis developed acute respiratory distress 12 hours after a fall. Blood gas analysis revealed hypoxia (PaO2 67.7 torr) and metabolic acidosis with an increased anion gap, consistent with lactic acidosis (lactate, 86.

DNA aptamer raised against advanced glycation end products inhibits melanoma growth in nude mice.

Epidemiological studies have suggested that diabetes is associated with an increased risk of cancer. However, the underlying molecular mechanism remains unclear. We investigated here whether DNA aptamer directed against advanced glycation end products (AGE-aptamer) inhibited melanoma growth in nude mice.

Beneficial effects of vildagliptin on retinal injury in obese type 2 diabetic rats.

Background/aims: Vildagliptin is an oral inhibitor of dipeptidyl peptidase-4, an enzyme mainly responsible for inactivating incretins, and one of the widely used drugs for the treatment of type 2 diabetes. However, effects of vildagliptin on retinal injury in diabetes remain unclear. We examined here whether oral administration of vildagliptin inhibited gene expression of inflammatory and thrombogenic parameters in Otsuka Long-Evans Tokushima Fatty rats (OLETF rats), an animal model of obese type 2 diabetes.

Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor.

Background: Advanced glycation end products (AGEs) and receptor RAGE interaction play a role in diabetic vascular complications. Inhibition of dipeptidyl peptidase-4 (DPP-4) is a potential therapeutic target for type 2 diabetes. However, the role of DPP-4 in AGE-induced endothelial cell (EC) damage remains unclear.

Sodium-glucose cotransporter 2-mediated oxidative stress augments advanced glycation end products-induced tubular cell apoptosis.

Background: Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is expressed mainly on the apical membrane of renal proximal tubules. Because blockade of SGLT2 promotes urinary glucose excretion and thereby improves hyperglycaemia, selective inhibition of SGLT2 has been proposed as a potential therapeutic target for the treatment of patients with diabetes. Moreover, advanced glycation end products (AGEs)-receptor (RAGE) system induces apoptosis of tubular cells, thereby playing a role in diabetic nephropathy as well.

Serum asymmetric dimethylarginine levels are independently associated with procollagen III N-terminal peptide in nonalcoholic fatty liver disease patients.

Although impaired synthesis and/or bioavailability of nitric oxide are considered to contribute to insulin resistance and the progression of liver disease in nonalcoholic fatty liver disease, role of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, has not been examined. We examined retrospectively which anthropometric and metabolic parameters were independently associated with serum levels of asymmetric dimethylarginine in nonalcoholic fatty liver disease. A total of 194 consecutive biopsy-proven nonalcoholic fatty liver disease patients with or without type 2 diabetes were enrolled.

Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end product-induced protein arginine methyltranferase-1 expression.

Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, contributes to diabetic nephropathy. We have found that glucagon-like peptide-1 (GLP-1) inhibits the AGE-induced inflammatory reactions in endothelial cells.