Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer.

BACKGROUND: Abundant evidence suggests that chronic inflammation is linked to prostate cancer and that infection is a possible cause of prostate cancer. METHODS: To identify microbiota or pathogens associated with prostate cancer, we investigated the transcriptomes of 20 human prostate cancer tissues. We performed de novo assembly of nonhuman sequences from RNA-seq data. RESULTS: We identified four bacteria as candidate microbiota in the prostate, including Moraxella osloensis, Uncultured chroococcidiopsis, Cutibacterium acnes, and Micrococcus luteus. Among these, C. acnes was detected in 19 of 20 prostate cancer tissue samples by immunohistochemistry. We then analyzed the gene expression profiles of prostate epithelial cells infected in vitro with C. acnes and found significant changes in homologous recombination (HR) and the Fanconi anemia pathway. Notably, electron microscopy demonstrated that C. acnes invaded prostate epithelial cells and localized in perinuclear vesicles, whereas analysis of γH2AX foci and HR assays demonstrated impaired HR repair. In particular, BRCA2 was significantly downregulated in C. acnes-infected cells. CONCLUSIONS: These findings suggest that C. acnes infection in the prostate could lead to HR deficiency (BRCAness) which promotes DNA double-strand breaks, thereby increasing the risk of cancer development.

Characterization of rice endosperm-derived antidepressant-like peptide (REAP): An orally active novel tridecapeptide derived from rice protein.

It is ideal to ingest bioactive substances from daily foods to stay healthy. Rice is the staple food for almost half of the human population. We found that an orally administered enzymatic digest of rice endosperm protein exhibits antidepressant-like effects in the tail suspension test (TST) using mice. A comprehensive peptide analysis of the digest using liquid chromatography-tandem mass spectrometry was performed, and a tridecapeptide QQFLPEGQSQSQK, detected in the digest, was chemosynthesized. Oral administration of the tridecapeptide exhibited antidepressant-like effects at a low dose comparable to classical antidepressant in the TST. This also exhibited anti-depressant-like effect in the forced swim test. We named it rice endosperm-derived antidepressant-like peptide (REAP). Intriguingly, intraperitoneal administration had no effect. Orally administered REAP(8-13) but not REAP(1-7) exhibited antidepressant-like activity, suggesting that the C-terminal structure is important for the antidepressant-like effect. We confirmed the presence of REAP, corresponding to rice glutelin type B4(130-142) and B5(130-142), in the digest. The effects of REAP were blocked by both dopamine D1 and D2 antagonists. These results suggest that it exerts its antidepressant-like activity through activation of the dopamine system. Taken together, oral administration of a novel tridecapeptide exhibited antidepressant-like effects via the dopamine system. This is the first report of a rice-derived peptide that exhibits antidepressant-like effects.

Rice Endoplasmic Protein-Derived Peptides, Rice-Ghretropins A and B, Stimulate Ghrelin Release in MGN3-1 Cells and Increase Plasma Acylated Ghrelin and Food Intake in Mice.

In this study, we demonstrated that novel rice-derived bioactive peptides promote the secretion of ghrelin, an endogenous orexigenic hormone secreted from the stomach. The enzymatic digest of rice endosperm protein with subtilisin, a microorganism-derived enzyme, stimulated acylated ghrelin secretion in the ghrelin-releasing cell line MGN3-1 and increased food intake after oral administration in mice. By performing a comprehensive analysis based on structure-activity relationships, we selected candidate peptides from over 30,000 peptides in the rice digest. Among them, we found that QAFEPIRSV and TNPWHSPRQGSF, corresponding to the amino acid sequence of the rice endoplasmic proteins glutelin A1 or A2(52-60) and B1 or B2(31-42), respectively, stimulated acylated ghrelin release in MGN3-1 cells. We named them rice-ghretropins A and B. Pyroglutamate formation of rice-ghretropin A, [pyr1]-rice-ghretropin A, also promoted ghrelin secretion. Furthermore, oral administration of rice-ghretropins increased food intake, plasma ghrelin concentration, and small intestinal transit in mice. In addition, the subtilisin digest of the rice protein significantly increased food intake for 4 h in 9 month-old (control: 0.61 ± 0.049 g; digest: 0.83 ± 0.059 g) and 24 month-old mice (control: 0.52 ± 0.067 g; digest: 1.01 ± 0.064 g). In summary, we found that novel bioactive peptides, namely, rice-ghretropins, from the enzymatic digest of rice endosperm stimulated acylated ghrelin secretion and increased food intake. This is the first report of rice-derived exogenous bioactive peptides that increase acylated ghrelin secretion.

Protective effects of hydrogen sulfide pretreatment on cyclophosphamide-induced bladder dysfunction in rats via suppression of bladder afferent nerves.

Cyclophosphamide (CYP), a broad-spectrum anticancer drug, causes serious side effects, such as haemorrhagic cystitis (HC). Hydrogen sulfide (H2S), an endogenous gasotransmitter, has physiological properties, including anti-inflammation, anti-oxidation, and neuromodulation. In this study, we investigated the effects of NaHS (H2S donor) pretreatment on bladder dysfunction in CYP-treated rats. Male Wistar rats were intraperitoneally pretreated with NaHS (3 or 10 µmol/kg) or vehicle once daily for 7 days before cystometry, and CYP (150 mg/kg) or saline was intraperitoneally administered 2 days before cystometry. After cystometry, the bladder tissues were collected for haematoxylin and eosin staining. In some rats, capsaicin (CAP), which can desensitise CAP-sensitive afferent nerves, was subcutaneously injected at 125 mg/kg 4 days before cystometry. CYP reduced intercontraction intervals (ICI) and bladder compliance (Comp) and increased the number of non-voiding contractions (NVCs) compared with the saline-treated control group. NaHS pretreatment dose-dependently improved the CYP-induced these changes. In bladder tissues, CYP increased histological scores of neutrophil infiltration, haemorrhage, and oedema, while NaHS had no effect on these CYP-induced changes. CAP showed a tendency to suppress CYP-induced changes in ICI. NaHS-induced improvement in CYP-induced changes in urodynamic parameters were not detected in CAP-treated rats. These findings suggest that NaHS pretreatment prevented bladder dysfunction in CYP-treated rats by suppressing CAP-sensitive bladder afferent nerves, but not by suppressing bladder inflammation. Therefore, H2S represents a new candidate as a protective drug for bladder dysfunction induced by HC, a side effect of CYP chemotherapy.

The draft genome sequence of the Brahminy blindsnake Indotyphlops braminus.

Blindsnakes of infraoder Scolecophidia (order Squamata) are the most basal group of extant snakes, comprising of more than 450 species with ecological and morphological features highly specialized to underground living. The Brahminy blindsnake, Indotyphlops braminus, is the only known obligate parthenogenetic species of snakes. Although the origin of I. braminus is thought to be South Asia, this snake has attracted worldwide attention as an alien species, as it has been introduced to all continents except Antarctica. In this study, we present the first draft genome assembly and annotation of I. braminus. We generated approximately 480 Gbp of sequencing data and produced a draft genome with a total length of 1.86 Gbp and N50 scaffold size of 1.25 Mbp containing 89.3% of orthologs conserved in Sauropsida. We also identified 0.98 Gbp (52.82%) of repetitive genome sequences and a total of 23,560 protein-coding genes. The first draft genome of I. braminus will facilitate further study of snake evolution as well as help to understand the emergence mechanism of parthenogenetic vertebrates.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVES: To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats. METHODS: Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry. Cystometry was performed under urethane anesthesia (0.8 g/kg, ip) via a catheter inserted into the bladder. After cystometry, bladder tissues were collected to perform hematoxylin and eosin staining for pathological evaluation (neutrophil infiltration, edema, and bleeding scores), and for enzyme-linked immunosorbent assay and real-time polymerase chain reaction for investigating tissue levels of myeloperoxidase, and mRNA levels of haem oxygenase-1 as a cytoprotective molecule. RESULTS: Compared to controls, cyclophosphamide induced a shorter intercontraction interval, lower bladder compliance, increased number of non-voiding contractions, and increased pathological scores and myeloperoxidase expression in the bladder. Pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (300/471 mg/kg/day) significantly improved cyclophosphamide-induced intercontraction interval shortening and increases in number of non-voiding contractions and neutrophil infiltration/bleeding scores and enhanced haem oxygenase-1 expression in the bladder. In addition, cyclophosphamide-induced decreases in bladder compliance and increases in myeloperoxidase were not detected with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate pretreatment. CONCLUSIONS: Pretreatment with 5-aminolevulinic acid expects protective effects on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis by improving inflammatory changes in bladder tissues perhaps via up-regulation of haem oxygenase-1.

The complete mitochondrial genome of a bagrid catfish, Tachysurus nudiceps, and its phylogenetic implications for the classification of the bagrid genera.

The complete sequence of the mitochondrial genome (mitogenome) of Tachysurus nudiceps (family Bagridae; order Siluriformes) was determined using next-generation sequencing. The composition of its mitogenome is the same as that observed in most other vertebrates and consists of 37 genes, an L-strand replication origin and a control region. As in previous studies, our phylogenetic analyses revealed that many of the bagrid genera are not monophyletic, emphasizing the necessity for reviewing and revising the taxonomy of this family at the genus level.

Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey.

Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.

Effects of losartan on bladder dysfunction due to aging-related severe hypertension in rats.

Aging is a major risk factor for bladder dysfunction. Anti-hypertensive drugs, angiotensin II type 1 receptor blockers (ARBs), are reported to ameliorate lower urinary tract dysfunction in rodent models and humans. We aimed to examine the preventive effect of an ARB, losartan, against bladder dysfunction due to aging-related severe hypertension. Male spontaneously hypertensive rats (SHRs) (36-week-old) were administered losartan (0, 3, or 10 mg/kg, p.o.) for 18 weeks. Age-matched, vehicle-treated Wistar Kyoto rats (WKYs) were used as controls. After the treatments, bladder and renal weight, mean blood pressure, and voiding parameters were measured. Additionally, detrusor thickness and bladder arterial wall thickness were evaluated using hematoxylin and eosin staining. Renal morphology was also assessed using periodic acid-Schiff staining. Compared to WKYs, SHRs demonstrated significantly higher bladder weight/body weight ratio (BBR), renal weight/body weight ratio, mean blood pressure, detrusor thickness, bladder arterial wall thickness, urine output, water intake, post-voiding residual urine volume, bladder capacity, intercontraction interval, and rate of glomerular and tubular injury and a lower urine osmolality. A low dose of losartan decreased the urine output, post-voiding residual urine volume, and bladder capacity in SHRs but not mean blood pressure in SHRs. A high dose of losartan decreased the BBR, mean blood pressure, detrusor thickness, bladder arterial wall thickness, post-voiding residual urine volume, bladder capacity, intercontraction interval, and glomerular and tubular injury in SHRs. Losartan inhibits bladder dysfunction in aged SHRs. The ARB losartan might be a preventive drug for bladder dysfunction due to aging-related severe hypertension.

Real-world experience with 5-aminolevulinic acid for photodynamic diagnosis of bladder cancer (2nd report): Reduced bladder recurrence after PDD-TURBT.

BACKGROUND: Photodynamic diagnosis (PDD) with administration of oral aminolevulinic acid (ALA) prior to transurethral resection of bladder tumor (TURBT) can now be used for non-muscle invasive bladder cancer (NMIBC) in clinical settings in Japan. Since ALA was first marketed, a limited number of reports have described PDD-TURBT outcomes, and the effects of resecting false-positive tissue on outcomes have not been clarified. METHODS: This study compared tumor recurrence among NMIBC patients who underwent TURBT under either white light cystoscopy (WL) or PDD. In addition, the frequency of recurrence was compared between patients with or without false-positive lesions at the time of PDD-TURBT. RESULTS: The frequency of recurrence in NMIBC patients (cumulative number of recurrences/cumulative number of follow-up days, number of recurrences/10,000 days), including progression to muscle-invasive bladder cancer (MIBC), was 12.80 in the WL-TURBT group and 5.82 in the PDD-TURBT group (p < 0.05). Tumor recurrence after TURBT was seen in 29 of 88 patients (33.0%) in the WL-TURBT group and 21 of 105 patients (20.0%) in the PDD-TURBT group (p < 0.05). Mean (± standard deviation) time to first recurrence was 249 ± 140 days in the WL-TURBT group and 419 ± 219 days in the PDD-TURBT group (p < 0.05). The frequency of recurrence in PDD-TURBT-group NMIBC patients was significantly lower in patients with resection of false-positive tissue (4.19/10,000 days) than in those without (9.00/10,000 days, p < 0.05). CONCLUSION: The frequency of recurrence was lower and the time to recurrence was longer in the PDD-TURBT group than in the WL-TURBT group. The frequency of recurrence decreased with resection of false-positive resection.

Current status of photodynamic technology for urothelial cancer.

5-Aminolevulinic acid is a new-generation photosensitizer with high tumor specificity. It has been used successfully in the diagnosis, treatment, and screening of urological cancers including bladder cancer; specifically, it has been used in photodynamic diagnosis to detect tumors by illuminating the lesion with a specific wavelength of light to produce fluorescence in the lesion after administration of 5-aminolevulinic acid, in photodynamic therapy, which induces tumor cell death via production of cytotoxic reactive oxygen species, and in photodynamic screening, in which porphyrin excretion in the blood and urine is used as a tumor biomarker after administration of 5-aminolevulinic acid. In addition to these applications in urological cancers, 5-aminolevulinic acid-based photodynamic technology is expected to be used as a novel strategy for a large number of cancer types because it is based on a property of cancer cells known as the Warburg effect, which is a basic biological property that is common across all cancers.

Murine remote ischemic preconditioning upregulates preferentially hepatic glucose transporter-4 via its plasma membrane translocation, leading to accumulating glycogen in the liver.

AIMS: We previously showed that hindlimb ischemia-reperfusion (IR) enhanced glucose uptake in the liver through the activation of the parasympathetic nervous system. Although we suggested that the key glucose transporter (GLUT) in this hepatic glucose uptake was GLUT4 by western blotting, the molecular weight of GLUT4 was nearly the same as that of GLUT2, which is predominantly expressed in the liver. We primarily conducted a histological evaluation to determine whether IR specifically accelerates the overexpression of GLUT4, rather than GLUT2, in the hepatocytes in vitro and in vivo. MAIN METHODS: A total of 54 male C57BL/6J mice were used and subjected to 3 min hindlimb ischemia repeated three times with 3 min interval. Focusing on the area connecting portal and central veins, the GLUT4 and GLUT2 expression in the hepatocytes were examined by real-time PCR and immunohistochemically. Moreover, the alteration of GLUT4 and GLUT2 expression by acetylcholine in the primary hepatocytes were examined by immunofluorescence. KEY FINDINGS: IR significantly upregulated the GLUT4, rather than GLUT2, expression in both mRNA and protein in the liver. Histological examination revealed marked glycogen storage in zone1, the periportal area, coincident with the enhanced GLUT4 immunoreactivity, in the IR-treated liver. Incubation of primary hepatocytes with acetylcholine induced the appearance of GLUT4 on the membrane peripheries. SIGNIFICANCE: The overexpression of GLUT4 on the membrane peripheries contributed to increasing glucose uptake found in IR-treated livers. This acceleration of glucose uptake via GLUT4 may induce marked glycogen storage in zone1 through energy production linked with increased glucose preference.

Aging-related severe hypertension induces detrusor underactivity in rats.

AIMS: Aging is an obvious risk factor for detrusor underactivity. We investigated the effects of aging on bladder function in spontaneously hypertensive rats. MAIN METHODS: Male spontaneously hypertensive rats and Wistar Kyoto rats (used as normotensive controls) at the ages of 18, 36, 54, or 72 weeks were used. Bladder weight, blood pressure, bladder blood flow, and urodynamic and renal parameters were measured. Additionally, detrusor thickness and renal histology were evaluated. KEY FINDINGS: In spontaneously hypertensive rats, significant increases were observed in bladder weight/body weight ratio, blood pressure, detrusor thickness, intercontraction interval, urine output, serum creatinine, and renal glomerular and tubular scores, and decreases in bladder blood flow and urine osmolality at 72 weeks as compared to those at 18 weeks. In spontaneously hypertensive rats, significant increases were observed in single voided volume, post voiding residual urine volume, and bladder capacity, with decrease in voiding efficiency were observed at 54 or 72 weeks than at 18 weeks. However, there were no significant differences in blood pressure, urodynamic and renal parameters, detrusor thickness and renal histology among Wistar Kyoto rats of different ages. SIGNIFICANCE: In spontaneously hypertensive rats, aging induces significant increases in blood pressure, single voided volume, post voiding residual urine volume, intercontraction intervals and urine output, and decreases in voiding efficiency and bladder blood flow indicative of detrusor underactivity. Aging-related severe hypertension could induce voiding dysfunction such as detrusor underactivity via severe bladder ischemia and polyuria. Aged spontaneously hypertensive rats may be useful animal models for detrusor underactivity.

Patterns of Natural Selection on Mitochondrial Protein-Coding Genes in Lungless Salamanders: Relaxed Purifying Selection and Presence of Positively Selected Codon Sites in the Family Plethodontidae.

There are two distinct lungless groups in caudate amphibians (salamanders and newts) (the family Plethodontidae and the genus Onychodactylus, from the family Hynobiidae). Lunglessness is considered to have evolved in response to environmental and/or ecological adaptation with respect to oxygen requirements. We performed selection analyses on lungless salamanders to elucidate the selective patterns of mitochondrial protein-coding genes associated with lunglessness. The branch model and RELAX analyses revealed the occurrence of relaxed selection (an increase of the dN/dS ratio = ω value) in most mitochondrial protein-coding genes of plethodontid salamander branches but not in those of Onychodactylus. Additional branch model and RELAX analyses indicated that direct-developing plethodontids showed the relaxed pattern for most mitochondrial genes, although metamorphosing plethodontids had fewer relaxed genes. Furthermore, aBSREL analysis detected positively selected codons in three plethodontid branches but not in Onychodactylus. One of these three branches corresponded to the most recent common ancestor, and the others corresponded with the most recent common ancestors of direct-developing branches within Hemidactyliinae. The positive selection of mitochondrial protein-coding genes in Plethodontidae is probably associated with the evolution of direct development.

Wheat-ghretropins: novel ghrelin-releasing peptides derived from wheat protein.

Ghrelin is an endogenous orexigenic hormone mainly produced by stomach cells and is reported to influence appetite, gastrointestinal motility and growth hormone secretion. We observed that enzymatic digest of wheat gluten stimulated ghrelin secretion from mouse ghrelinoma 3-1, a ghrelin-releasing cell line. Further on, we characterized the ghrelin-releasing peptides present in the digest by comprehensive peptide analysis using liquid chromatography-mass spectrometry and structure-activity relationship. Among the candidate peptides, we found that SQQQQPVLPQQPSF, LSVTSPQQVSY and YPTSL stimulated ghrelin release. We then named them wheat-ghretropin A, B and C, respectively. In addition, we observed that wheat-ghretropin A increased plasma ghrelin concentration and food intake in mice after oral administration. Thus, we demonstrated that wheat-ghretropin stimulates ghrelin release both in vitro and in vivo. To the best of our knowledge, this is the first report of a wheat-derived exogenous bioactive peptide that stimulates ghrelin secretion.

Non-neuronal cardiac acetylcholine system playing indispensable roles in cardiac homeostasis confers resiliency to the heart.

BACKGROUND: We previously established that the non-neuronal cardiac cholinergic system (NNCCS) is equipped with cardiomyocytes synthesizes acetylcholine (ACh), which is an indispensable endogenous system, sustaining cardiac homeostasis and regulating an inflammatory status, by transgenic mice overexpressing choline acetyltransferase (ChAT) gene in the heart. However, whole body biological significances of NNCCS remain to be fully elucidated. METHODS AND RESULTS: To consolidate the features, we developed heart-specific ChAT knockdown (ChATKD) mice using 3 ChAT-specific siRNAs. The mice developed cardiac dysfunction. Factors causing it included the downregulation of cardiac glucose metabolism along with decreased signal transduction of Akt/HIF-1alpha/GLUT4, leading to poor glucose utilization, impairment of glycolytic metabolites entering the tricarboxylic (TCA) cycle, the upregulation of reactive oxygen species (ROS) production with an attenuated scavenging potency, and the downregulated nitric oxide (NO) production via NOS1. ChATKD mice revealed a decreased vagus nerve activity, accelerated aggression, more accentuated blood basal corticosterone levels with depression-like phenotypes, several features of which were accompanied by cardiac dysfunction. CONCLUSION: The NNCCS plays a crucial role in cardiac homeostasis by regulating the glucose metabolism, ROS synthesis, NO levels, and the cardiac vagus nerve activity. Thus, the NNCCS is suggested a fundamentally crucial system of the heart.

Cutaneous acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia with proliferation of mature sebocytes: A case report.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Murine remote ischemic preconditioning suppresses diabetic ketoacidosis by enhancing glycolysis and entry into tricarboxylic acid cycle in the liver.

AIMS: Hindlimb ischemia-reperfusion (IR) was previously demonstrated by our group to decrease blood sugar levels by suppressing hepatic gluconeogenesis and enhancing glucose uptake using activation of the parasympathetic nervous system. While IR attenuated hyperglycemia in diabetic mice, it was unclear whether IR regulated energy metabolism in the liver. We investigated the mechanisms by which IR regulates energy metabolism in the liver from type1 diabetic mice. MAIN METHODS: Streptozotocin-induced diabetic male C57BL/6J mice were used to determine the effect of IR on the factors involved in energy metabolism in the liver (i.e., activation levels of AMP-activated protein kinase, aconitase and pyruvate dehydrogenase; adenosine triphosphate and fumarate concentrations; sirtuin (Sirt) 1 expression). These various signaling pathways and key enzyme activities were examined using western blot analysis and a biochemical technique including a colorimetric assay. KEY FINDINGS: Under feeding conditions (free access to normal murine chow and water), blood glucose levels and serum ketone body levels were significantly suppressed by IR, whereas phospho-AMP-activated protein kinase and its activity, pyruvate dehydrogenase, aconitase activity, and Sirt 1expression were upregulated. In contrast, peroxisome proliferator-activated receptor γ coactivator-1, which accelerated fatty acid use, was suppressed by IR. SIGNIFICANCE: These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Therefore, IR may be beneficial against diabetic hyperglycemia, but also ketoacidosis.

Superficial Angiomyxoma of the Nipple in a Japanese Woman: A Case Report and Review of Literature.

Superficial angiomyxoma is a rare, benign, multilobulated cutaneous tumor composed of stellate and spindle cells, a prominent myxoid matrix, and numerous blood vessels. Superficial angiomyxoma may be indistinguishable from cutaneous lesions of the Carney complex, although superficial angiomyxoma can occur independently of the complex. In this article, we present the case of a 39-year-old Japanese woman with a 40 × 30 mm, focally ulcerated, polypoid superficial angiomyxoma on the left nipple without any evidence of Carney complex. The development of superficial angiomyxoma on the nipples in a patient without the Carney complex is extremely rare. Indeed, only 3 cases of superficial angiomyxoma arising on the nipple have been reported to date, and this is the first such report in Japan. In such cases, the majority of superficial angiomyxoma of the nipples develop in premenopausal women. The possibility of superficial angiomyxoma should be considered for all polypoid nipple lesion, particularly in premenopausal women, and complete excision with follow-up observation should be performed.