SOD2 mRNA as a potential biomarker for exercise: interventional and cross-sectional research in healthy subjects

The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono­nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034).     

Role of prostaglandins on mechanical scratching-induced cutaneous barrier disruption in mice

The role of prostaglandins (PGs) on mechanical scratching-induced cutaneous barrier disruption in mice was investigated by comparing the observed effects of arachidonic acid (AA) application. Scratching of the mouse skin with a stainless-steel wire brush (mechanical scratching) was associated with significant, scratch-count-dependent elevation of the transepidermal water loss (TEWL) and skin PG levels (especially PGD(2) and PGE(2)). Histological evidence of inflammation (crusta, acanthosis and neutrophilic infiltration) in the skin also became evident 24 h after mechanical scratching. On the other hand, while topical application of 0.1% AA to the mouse skin also increased the skin PG levels, but did not produce any increase of TEWL or histological evidence of inflammation in the skin. Topical application of cyclooxygenase inhibitors (indomethacin, piroxicam, aspirin, diclofenac and ketoprofen) decreased the spontaneous recovery rates from cutaneous barrier disruption. These results suggest that the elevation of cutaneous PG production induced by mechanical scratching is involved in the repair of the skin damage caused by the scratching.     

Reticulated acanthoma with sebaceous differentiation

Reticulated acanthoma with sebaceous differentiation (RASD) is characterized by the reticulated proliferation of spinous cells with aggregates of mature sebocytes in the bases of the strands of the keratinocytes, often linking rete ridges. Here, we report the first case reported as RASD. A 55-year-old woman presented with a 15-year history of a slightly pruritic patch on the upper back, and the histology was typical for RASD. She had been bothered by a yellow discharge from the tumor. Skin tumors with sebaceous differentiation are occasionally associated with Muir-Torre syndrome. However, immunohistochemical staining for mutS homolog 2 (MSH-2) and mutL homolog 1 (MLH-1) showed positive staining within the nuclei of sebaceous cells and cells in the dermis. Therefore, it is most likely that the present case is not associated with Muir-Torre syndrome.     

P‐ANCA‐positive Wegener’s granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: Case report and review of literature

An autopsy case of hypertrophic pachymeningitis and multiple cranial neuropathies is reported. A 53‐year‐old woman with paraplegia and various neurological signs which developed over a 2 year period was diagnosed as having an epidural mass with thickened dura mater extending from the lower cervical to the thoracic spinal cord. In addition, bilateral episcleritis, blephaloptosis, and blindness of the right eye with various cranial nerve deficits were found to be caused by the mass lesions involving the paranasal sinuses, orbit, and the cavernous sinus. Perinuclear antineutrophil cytoplasmic antibody (p‐ANCA) was positive, but cytoplasmic antineutrophil cytoplasmic antibody (c‐ANCA) was negative by enzyme‐linked immunosorbent assay. The partially removed epidural mass with hypertrophied dura mater and biopsy of the paranasal lesions showed chronic granulomatous inflammation with vasculitis. The remaining lesions resolved with steroid therapy with remarkable neurological improvement. The positive p‐ANCA test, paranasal involvement, the report of a similar histopathological case and a review of the literature on granulomatous pachymeningitis suggest the presence of p‐ANCA‐positive Wegener’s granulomatosis with central nervous system involvement characterized by hypertrophic pachymeningitis and/or multiple cranial neuropathies.     

Mild exercise suppresses exacerbation of dermatitis by increasing cleavage of the β-endorphin from proopiomelanocortin in NC/Nga mice

This study investigated the mechanism by which the strength and weakness of exercise stress affects the skin symptoms of atopic dermatitis (AD). Specific pathogen-free (SPF) and conventional NC/Nga mice were used. Conventional mice, but not the SPF, spontaneously develop dermal symptoms similar to that of patients with AD. There were two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The symptom of the conventional group were strongly exacerbated by strong exercise but ameliorated by mild exercise. The plasma concentrations of α-melanocyte stimulating hormone (α-MSH) and the expression of melanocortin receptor-1 in skin elevated after strong exercise but decreased after mild exercise. The plasma levels of β-endorphin and the expression of µ-opioid receptor in skin were increased by mild exercise. In addition, the expression of prohormone convertase (PC) 1/3, PC2 and carboxypeptidase E (CPE) in pituitary gland were higher in the conventional group than in the SPF group. The level of PC2 was suppressed by mild exercise in the conventional groups, and elevated further by strong exercise. The level of PC1/3 becomes higher with the increase of the exercise load. On the other hand, the expression of the CPE was further increase by mild exercise but suppressed by strong exercise. These observations suggested that exercise-induced stress significantly affect the symptoms of AD in a pivotal manner depending on the levels of α-MSH and β-endorphin, and the expression of pituitary PC2 and CPE.     

Detection of axillary node metastasis using diffusion-weighted MRI in breast cancer

Breast magnetic resonance imagings (MRIs) including diffusion-weighted MRI (DWI) of 110 breast cancers (26 with pathologically proven axillary node metastasis and 84 without metastasis) were retrospectively studied. Axillary nodes were detected as high-signal-intensity areas on DWI in 71 cancers (24 with metastasis and 47 without) and not detected in 39 cancers (2 with metastasis and 37 without). The ADC of metastatic nodes was significantly greater than that of the benign ones (1.08±0.18×10^?3 mm²/s vs. 0.92±0.22×10^?3 mm²/s, P=.004). When detectability of axillary nodes on DWI and ADC over 1.05×10^?3 mm²/s was applied as a threshold, 53.8% sensitivity, 86.9% specificity, and 79.1% accuracy were provided.     

Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non-remission acute myeloid leukaemia: A nationwide retrospective study

Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some patients with acute myeloid leukaemia (AML) who are refractory to chemotherapy. Cord blood transplantation (CBT) is a reasonable option in such cases because of its rapid availability. Recently, a growing number of human leucocyte antigen (HLA)-haploidentical related donor HSCTs (haplo-HSCTs) have been performed, although its effectiveness remains undetermined. Using the Japanese nationwide transplantation registry data, we identified 2438 patients aged ≥16 years who received CBT or haplo-HSCT as their first transplant for non-remission AML between January 2008 and December 2018. After 2:1 propensity score matching, 918 patients in the CBT group and 459 patients in the haplo-HSCT group were selected. In this matched cohort, no significant difference in overall survival (OS) was observed between the CBT and haplo-HSCT groups (hazard ratio [HR] of haplo-HSCT to CBT 1.02, 95% confidence interval [CI] 0.89–1.16). Similarly, no significant difference in the cumulative incidence of relapse (HR 1.09, 95% CI 0.93–1.28) or non-relapse mortality (HR 0.94, 95% CI 0.76–1.18). Subgroup analysis showed that CBT was significantly associated with preferable OS in patients receiving myeloablative conditioning. Our data showed comparable outcomes between haplo-HSCT and CBT recipients with non-remission AML.     

Cyclic AMP differentially regulates cell proliferation of normal human keratinocytes through ERK activation depending on the expression pattern of B-Raf

Intracellular cyclic AMP (cAMP) increased by extracellular stimuli induces various biological effects, such as cell proliferation, differentiation, and migration. Previous reports regarding the effect of cAMP on keratinocyte proliferation are contradictory and indicate that the effect apparently depends on cellular density. Recent studies have revealed that cAMP signaling regulates cell proliferation by modulating mitogen-activated protein kinase (MAPK) activity. The precise mechanism by which cAMP affects keratinocyte proliferation and/or the crosstalk between the cAMP and MAPK signaling pathways, however, remain to be determined. Using normal human keratinocytes (NHK), we investigated the effect of cAMP on keratinocyte proliferation and its molecular mechanism in terms of cellular density. In confluent NHK, cyclic AMP decreased extracellular regulated kinase (ERK) phosphorylation and cell proliferation in a Ras-independent and Rap1-dependent manner. The decreased cell proliferation by cAMP was blocked by the MEK-1 inhibitor, PD98059. In contrast, in subconfluent NHK, cAMP increased ERK phosphorylation and cell proliferation. Western blot analysis revealed that NHK expressed B-Raf and Rap-1. Although both 95 kDa and 62 kDa B-Raf isoforms were expressed in subconfluent NHK, only 62 kDa B-Raf was detected in confluent NHK. Transfection of 95 kDa B-Raf into confluent NHK resulted in a cAMP-dependent increase in ERK phosphorylation and cell proliferation. These findings indicate that differential expression of B-Raf isoforms is critical for cAMP-dependent regulation of NHK proliferation that depends on phosphorylation of ERK.