Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect.

Breynia spp. are a key source of sulfur-containing spiroketal glycosides with potential anti-inflammatory activity. In this study, three new sulfur-containing spiroketals - breynin J (1), epibreynin J (2), and probreynogenin (3) - along with four known compounds - probreynin I (4), phyllaemblic acid (5), breynin B (6), and epibreynin B (7) - were isolated from the roots of Breynia disticha. The structures of compounds 1-7 were elucidated by extensive 1D and 2D NMR spectroscopic analyses, including 1D total correlation spectroscopy (TOCSY), HSQC, HMBC, double quantum-filtered (DQF)-COSY, heteronuclear two-bond correlation (H2BC), and HSQC-TOCSY experiments, as well as high-resolution electrospray ionization HRESIMS analysis, and quantum chemical electronic CD calculations. Furthermore, the absolute configurations of sugar residues were determined by derivatization of the hydrolysates with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. The anti-inflammatory effects of the isolated compounds were evaluated based on the mRNA levels of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Compounds 1, 2, 6, and 7 inhibited the increase in interleukin (IL)-1ß and IL-6 mRNA levels stimulated by LPS. Moreover, the most potent compound 7 was found to significantly inhibit the production of IL-1ß and IL-6 proteins, as revealed by the analysis of culture supernatants.

The combined effect of rowing exercise and the intake of functional foods containing inulin on muscle mass and bone mineral density in older Japanese women.

AIM: Aging decreases muscle mass and bone mineral density (BMD), especially in older women. It has been reported that rowing and inulin intake positively affect muscle and bone, respectively. We examined the synergistic effect of rowing and functional food intake, including inulin, on lean body mass, BMD, and physical function parameters in older Japanese women. METHODS: Fifty women aged 65-79 years were divided into four groups with or without inulin intake and rowing. The interventions were carried out for 12 weeks in each group. We assessed lean body mass and BMD using dual-energy X-ray absorptiometry at baseline and after the intervention and examined the changes in the values in each group. RESULTS: Lean body mass in all groups decreased, and the change in lean body mass in the group with rowing and inulin intake was significantly smaller than that in the group without them (-0.05 ± 0.61; -0.83 ± 0.59 kg; P = 0.030). The BMD in the three intervention groups increased after the 12-week intervention. The change in BMD in each of the three intervention groups showed significant differences compared with the control group (Rowing + Inulin: P = 0.03; Rowing + No inulin: P = 0.01; No rowing + Inulin: P < 0.01). CONCLUSIONS: Rowing and the intake of functional foods, including inulin, synergistically prevented a decrease in lean body mass. These factors, individually and additively, might increase BMD in older Japanese women. Geriatr Gerontol Int 2023; 23: 779-787.

Diagnosis, Treatment, and Prevention of Ileostomy Complications: An Updated Review.

An ileostomy is associated with multiple complications that may frequently or persistently affect the life of ostomates. All healthcare professionals should have knowledge of the diagnosis, treatment, and prevention of ileostomy complications. Peristomal dermatitis is caused by watery and highly alkaline effluent. Skin protective products are typically used for local treatment. Ischemia/necrosis occurs due to insufficient arterial blood supply. Retraction is seen in patients with a bulky mesentery and occurs following ischemia. Convex stoma appliances can be used for skin protection against fecal leakage. Small bowel obstruction (SBO) is common and occurs only at the stoma site. Trans-stomal decompression is most effective in these cases. High output stoma (HOS) is defined as a condition when the output exceeds 1,000- 2,000 ml/day, lasting for one to three days. Treatment includes intravenous fluid and electrolyte resuscitation followed by restriction of hypotonic fluid and the use of antimotility (and antisecretory) drugs. Stomal prolapse is a full-thickness protrusion of an inverted bowel. Manual reduction is attempted initially, whereas emergency bowel resection may be needed for incarcerated cases. A parastomal hernia (PSH) is an incisional hernia of the stoma site. Surgery is considered in cases of incarceration, but most cases are manageable with non-surgical treatment.

Comparison between DXA and MRI for the Visceral Fat Assessment in Athletes.

The use of dual-energy X-ray absorptiometry (DXA) may be invalid for assessing athletes with larger bodies, larger lean body mass, and thicker trunks. This study compared the athletes' visceral adipose tissue (VAT) assessed using DXA and magnetic resonance imaging (MRI). Eighty-two Japanese male collegiate athletes from 18 sports participated in this study. VAT was assessed using the dual-energy scan that coincided with the 4th lumbar vertebra. The sum of eight magnetic resonance slices corresponding to the region of the dual-energy scan was used for comparison. The VAT volume was higher with the dual-energy scan than with MRI (difference: 35 cm3, p<0.01). A significant correlation was noted between the volumes measured using both modalities (r=0.88, p<0.01). Magnetic resonance-derived volumes less than 600 cm3 showed a stronger significant correlation with dual-energy-derived volumes. However, magnetic resonance-derived VAT volumes exceeding 600 cm3 were not significantly correlated with dual-energy-derived volumes. In conclusion, VAT volumes derived from DXA were larger and significantly correlated with those derived from MRI across a wide range of values. Methods using DXA for assessing the visceral fat volume may require adjustment to estimate abdominal visceral fat volume in athletes, with care taken when using such methods for heavyweight athletes.

Increasing Meal Frequency in Isoenergetic Conditions Does Not Affect Body Composition Change and Appetite During Weight Gain in Japanese Athletes.

For athletes to gain body mass, especially muscle, an increase in energy consumption is necessary. To increase their energy intake, many athletes consume more meals, including supplementary meals or snacks. However, the influence of meal frequency on changes in body composition and appetite is unclear. The aim of this study was to determine the effect of meal frequency on changes in body composition and appetite during weight gain in athletes through a well-controlled dietary intervention. Ten male collegiate rowers with weight gain goals were included in this study. The subjects were randomly classified into two groups, and dietary intervention was implemented using a crossover method. During the intervention period, all subjects were provided identical meals aimed to provide a positive energy balance. The meals were consumed at a frequency of either three times (regular frequency) or six times (high frequency) a day. Body composition was measured using dual energy X-ray absorptiometry, and the visual analog scale was used for the evaluation of appetite. In both trials, body weight, fat-free mass, and fat mass significantly increased; however, an interaction (Trial × Time) was not observed. Visual analog scale did not vary between trials. Our data suggest that partitioning identical excess dietary intakes over three or six meals does not influence changes in body composition or appetite during weight gain in athletes.

Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan.

BACKGROUND: The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer. METHODS: We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics. RESULTS: The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044). CONCLUSION: More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

Two cases of spindle cell variant diffuse large B-cell lymphoma of the uterine cervix.

Lymphoma with prominent spindle cell features is a morphological variant of diffuse large B-cell lymphoma (DLBCL) and is categorized as a rare variant by the WHO classification. Most cases arise from the skin, with only two cases reported in the uterine cervix to date. Here, we report two cases of spindle cell variant DLBCL of the uterine cervix. Although these cases might be rare, we believe that, as gynecologists and pathologists increase their knowledge of this variant type, more cases will be diagnosed properly.

Validity of Combination Use of Activity Record and Accelerometry to Measure Free-Living Total Energy Expenditure in Female Endurance Runners.

Yoshida, A, Ishikawa-Takata, K, Tanaka, S, Suzuki, N, Nakae, S, Murata, H, Taguchi, M, and Higuchi, M. Validity of combination use of activity record and accelerometry to measure free-living total energy expenditure in female endurance runners. J Strength Cond Res 33(11): 2962-2970, 2019-Herein, we attempted to prove the validity of a new approach to assessing total energy expenditure (TEE) that combines activity recording and accelerometry in athletes. Eight female endurance runners participated in this study. We measured TEE over 8 days in the regular training season by using the doubly labeled water (DLW) method. In the combined method, an activity record of the rating of perceived exertion (RPE) was used to estimate energy expenditure (EE) during the training period, whereas a triaxial accelerometer was used to evaluate EE during the nontraining time over the TEE measurement period using the DLW method. Training EE was calculated from the subjects' individual rating of perceived exertion-EE correlations provided by the exercise tolerance test. Resting metabolic rate (RMR) was measured using indirect calorimetry. There were no significant differences in TEE, activity-induced EE (AEE), or physical activity level (PAL; TEE/RMR) between the DLW method and the combined method (TEE, 3,032 ± 344 vs. 3,033 ± 495 kcal·d; AEE, 1,585 ± 303 vs. 1,586 ± 442 kcal·d; and PAL, 2.68 ± 0.37 vs. 2.68 ± 0.48, respectively). Significant positive correlations and no systematic errors were observed in AEE and PAL. Intraclass correlation coefficients were high (TEE, 0.785; AEE, 0.841; and PAL, 0.779, respectively). These findings suggest that the combined method has high validity against the DLW method. Thus, the combined method would be able to estimate free-living TEE in the regular training season for female endurance runners.

Gerontoxanthone B from Maclura cochinchinensis var. gerontogea exhibits anti-inflammatory potential as an aryl hydrocarbon receptor agonist.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor belonging to the basic helix-loop-helix-Per-Ahr/Arnt-Sim family. In this study, we evaluated the AhR agonistic activities of 12 xanthones isolated from the roots of M. cochinchinensis var. gerontogea using HepG2 cells transfected with pX4TK-Luc reporter plasmids. Gerontoxanthone B (GXB) showed the most potent activity at a concentration of 10µM, and the activity was inhibited by AhR antagonists such as GNF-351. GXB also increased cytochrome P450 1A1 mRNA and protein levels in HepG2 cells. Similar to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin, however, GXB suppressed the IL-1ß-induced mRNA level of SAA1, an acute-phase response gene that is up-regulated AhR-dependently but XRE-independently. Thus, GXB shows XRE-dependent transcriptional activity and XRE-independent activity involving AhR.

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C.

BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. RESULTS: We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). CONCLUSIONS: On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

Characteristics of body composition and cardiometabolic risk of Japanese male heavyweight Judo athletes.

BACKGROUND: The purpose of this study was to clarify the characteristics of body composition and cardiometabolic risk of Japanese male heavyweight Judo athletes compared with heavyweight athletes of other sports. METHODS: Nineteen heavyweight Judo athletes (mean age, 20.4 ± 1.1 years), as well as 22 heavyweight (mean age, 21.5 ± 0.9 years) and 17 nonheavyweight (mean age, 21.1 ± 0.8 years) American football and Rugby football athletes in Japan participated in this study. Body composition was assessed by using dual-energy X-ray absorptiometry and magnetic resonance imaging. Cardiometabolic risk was evaluated by measuring blood biochemical variables. RESULTS: Heavyweight Judo athletes had significantly heavier body mass (122.7 ± 13.1 kg vs. 99.0 ± 8.1 kg), higher body fat percentage (27.5 % ± 5.2% vs. 19.4% ± 4.7%), and larger visceral fat cross-sectional area (118 ± 35 cm(2) vs. 67 ± 24 cm(2)) (P < 0.01) compared with heavyweight football players. Although the cardiometabolic risk was higher in heavyweight athletes compared to nonheavyweight athletes, there were no significant differences between heavyweight Judo and heavyweight Football athletes in the blood biochemical variables, except for high concentration of uric acid in heavyweight Judo athletes. CONCLUSIONS: Even though heavyweight Judo athletes had more excess fat mass, especially VF mass, their cardiometabolic risk in terms of blood biochemical parameters was not significantly higher compared with heavyweight athletes of other sports. Therefore, excessive fat accumulation may not necessarily increase cardiometabolic risk for heavyweight Judo athletes. TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network Clinical Trial Registration (UMIN-CTR) UMIN000020564.

Xanthones from the roots of Maclura cochinchinensis var. gerontogea and their retinoic acid receptor-α agonistic activity.

A new xanthone (1) and a new naturally occurring xanthone (2) were isolated from the roots of Maclura cochinchinensis (Lour.) Corner var. gerontogea (Sieb. et Zucc.) Ohashi together with 10 known xanthones (3-12). Their structures were established by spectroscopic analyses including 1D and 2D NMR. Their retinoic acid receptor-α agonistic activity was evaluated using a luciferase reporter assay. Compound 2, gerontoxanthone A (3), gerontoxanthone B (4), and cudraxanthone I (11) showed moderate concentration-dependent activity. Furthermore, these four xanthones synergistically increased transcriptional activity in this assay in the presence of bexarotene, an RXR agonist.

Prominent steatosis with hypermetabolism of the cell line permissive for years of infection with hepatitis C virus.

Most of experiments for HCV infection have been done using lytic infection systems, in which HCV-infected cells inevitably die. Here, to elucidate metabolic alteration in HCV-infected cells in a more stable condition, we established an HCV-persistently-infected cell line, designated as HPI cells. This cell line has displayed prominent steatosis and supported HCV infection for more than 2 years, which is the longest ever reported. It enabled us to analyze metabolism in the HCV-infected cells integrally combining metabolomics and expression arrays. It revealed that rate-limiting enzymes for biosynthesis of cholesterol and fatty acids were up-regulated with actual increase in cholesterol, desmosterol (cholesterol precursor) and pool of fatty acids. Notably, the pentose phosphate pathway was facilitated with marked up-regulation of glucose-6-phosphate dehydrogenase, a rete-limiting enzyme, with actual increase in NADPH. In its downstream, enzymes for purine synthesis were also up-regulated resulting in increase of purine. Contrary to common cancers, the TCA cycle was preferentially facilitated comparing to glycolysis pathway with a marked increase of most of amino acids. Interestingly, some genes controlled by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of antioxidation and metabolism, were constitutively up-regulated in HPI cells. Knockdown of Nrf2 markedly reduced steatosis and HCV infection, indicating that Nrf2 and its target genes play important roles in metabolic alteration and HCV infection. In conclusion, HPI cell is a bona fide HCV-persistently-infected cell line supporting HCV infection for years. This cell line sustained prominent steatosis in a hypermetabolic status producing various metabolites. Therefore, HPI cell is a potent research tool not only for persistent HCV infection but also for liver metabolism, overcoming drawbacks of the lytic infection systems.

Obscure gastrointestinal bleeding: resection of a pyogenic granuloma of the ileum via double-balloon enteroscopy.

Pyogenic granulomas usually occur on the skin or oral mucosa; however, they rarely develop in the gastrointestinal tract, particularly in the ileum. We report the case of an 82-year-old female who experienced occasional bloody stools. Initially, no significant bleeding source could be identified via conventional endoscopy; however, repeat capsule endoscopy identified a bleeding polyp (8 mm) in the ileum. Therefore, we resected the polyp via double-balloon enteroscopy. Histopathological findings showed increased, lobulated, and enlarged capillaries and desquamated epithelium indicative of epithelial erosion. In addition, neutrophil-predominant inflammatory cell infiltrate and interstitial edema were observed in the intercapillary stroma. Immunohistochemical analysis showed positive staining for vascular endothelial cell markers. Previous reports have mentioned that pyogenic granulomas in the oral cavity were associated with the female hormonal receptor, vascular endothelial growth factor, and proliferative immune markers; however, no significant staining was observed in our patient. This is the first report discussing an association between pyogenic granulomas and these markers. Pyogenic granulomas in the ileum are rare and may cause fatal anemia. Pyogenic granulomas should be considered in the differential diagnosis of obscure gastrointestinal bleeding.

Encephalomalacia in surviving twin after single fetal death diagnosed at 18 weeks of gestation in monochorionic twin pregnancy.

PATIENT: Female, 28 FINAL DIAGNOSIS: Single intrauterine fetal death Symptoms: - MEDICATION: - Clinical Procedure: - Specialty: Obstetrics and Gynecology. OBJECTIVE: Rare disease. BACKGROUND: Single fetal death in monochorionic twin pregnancy may result in poor perinatal outcome of the surviving twin, including neurologic sequelae, other organ injury, and death. In most reported cases of poor perinatal outcome in the surviving twin, monochorionic co-twin death occured after more than 20 weeks of gestation, while few with earlier occurrence have been presented. CASE REPORT: A 28-year-old primigravid woman was referred to our hospital at 18 3/7 weeks of gestation for perinatal management of single fetal death in a monochorionic-diamniotic twin pregnancy. Our first evaluation by ultrasonography revealed a dead twin sized at 16 weeks of gestation, and an alive one with normal size and appearance, together with 1 placenta and 2 amniotic cavities with normal fluid amounts. At 20 3/7 weeks of gestation, ultrasonography showed that the surviving twin had bilateral ventriculomegaly and dilatation all around the subarachnoid cavity despite a normal head size. Fetal magnetic resonance imaging revealed remarkable atrophy of the cerebral cortex. After counseling, the patient and family chose termination of pregnancy, and artificial abortion was performed at 21 weeks of gestation. The aborted fetuses were not anomalous. Autopsy pathological findings confirmed encephalomalacia in the surviving twin. CONCLUSIONS: Recent development of imaging device make it possible that several abnormalities in central nervous system can be detected in detail at earlier gestational age. It is important to keep this condition in mind even though single fetal death occurred at early gestational age.

New glycosides of acetophenone derivatives and phenylpropanoids from Juniperus occidentalis.

New glycosides of seven acetophenone derivatives (1-7) and two phenylpropanoids (8, 9), named juniperosides III-XI, have been isolated from the MeOH extract of the leaves and stems of Juniperus occidentalis Hook. (Cupressaceae), together with eleven other known compounds. The structures of these compounds have been successfully elucidated using a variety of spectroscopic techniques.

6-year periodicity and variable synchronicity in a mass-flowering plant.

Periodical organisms, such as bamboos and periodical cicadas, are very famous for their synchronous reproduction. In bamboos and other periodical plants, the synchronicity of mass-flowering and withering has been often reported indicating these species are monocarpic (semelparous) species. Therefore, synchronicity and periodicity are often suspected to be fairly tightly coupled traits in these periodical plants. We investigate the periodicity and synchronicity of Strobilanthes flexicaulis, and a closely related species S. tashiroi on Okinawa Island, Japan. The genus Strobilanthes is known for several periodical species. Based on 32-year observational data, we confirmed that S. flexicaulis is 6-year periodical mass-flowering monocarpic plant. All the flowering plants had died after flowering. In contrast, we found that S. tashiroi is a polycarpic perennial with no mass-flowering from three-year individual tracking. We also surveyed six local populations of S. flexicaulis and found variation in the synchronicity from four highly synchronized populations (>98% of plants flowering in the mass year) to two less synchronized one with 11-47% of plants flowering before and after the mass year. This result might imply that synchrony may be selected for when periodicity is established in monocarpic species. We found the selective advantages for mass-flowering in pollinator activities and predator satiation. The current results suggest that the periodical S. flexicaulis might have evolved periodicity from a non-periodical close relative. The current report should become a key finding for understanding the evolution of periodical plants.

Three new constituents from the roots of Erythrina variegata and their antibacterial activity against methicillin-resistant Staphylococcus aureus.

Two new isoflavonoids, eryvarins V and W (1 and 2, resp.), and a new chromen-4-one derivative, eryvarin X (3), along with three known isoflavonoids, 4-6, were isolated from the roots of Erythrina variegata. Their structures were established by spectroscopic analyses. Compound 1 is a rare naturally occurring isoflavanone which possesses a OH group at C(3). Among the new compounds 1-3, 2 exhibited a potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains.