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.

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.

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.

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.

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.

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.

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.

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.

New phenylpropanoid glycosides from Juniperus communis var. depressa.

Two new phenylpropanoid glycosides were isolated from the leaves and stems of Juniperus communis var. depressa (Cupressaceae) along with 14 known compounds. Their structures were determined by spectral analyses, in particular by 2D-NMR spectral evidence.

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.

24-Ethyl,24-methyl-29-nor-lanostanes from leaves of Freycinetia formosana.

Two new 24-ethyl,24-methyl-29-nor-lanostanes (1, 2) were isolated from the MeOH extract of leaves of Freycinetia formosana (Pandanaceae). Their structures were elucidated based on spectroscopic evidence.

Solution structure of the variable-type domain of the receptor for advanced glycation end products: new insight into AGE-RAGE interaction.

Diabetes is defined by chronic hyperglycemia due to deficiency in insulin action. It has been found that the amount of advanced glycation end products (AGE) from the Maillard reaction between proteins and sugar molecules increases in blood of diabetic patients and furthermore that AGE binding to their cell surface receptor (RAGE) triggers both macrovascular and microvascular impairments to cause diabetic complications. Due to the clinical significance of the vascular complications, RAGE is currently a focus as an attractive target for drug discovery of candidates which interfere with AGE-RAGE binding to prevent the subsequent intracellular signaling related to pathogenical effects. Here, we determined the three-dimensional structure of the recombinant AGE-binding domain by using multidimensional heteronuclear NMR spectroscopy and showed that the domain assumes a structure similar to those of other immunoglobulin V-type domains. The site-directed mutagenesis studies identified the basic amino acids which play a key role in the AGE binding activities. Our results obtained from this study provide new insight into AGE-RAGE interaction.

Isolation of apoptosis- and differentiation-inducing substances toward human promyelocytic leukemia HL-60 cells from leaves of Juniperus taxifolia.

A chloroform extract of the leaves of Juniperas taxifolia exhibited a marked antiproliferative effect on human promyelocytic leukemia HL-60 cells at a concentration of 2.5 microg/ml. Deoxypodophyllotoxin (4) was identified in the extract as an outstanding antiproliferative compound, and five diterpenes (1-3, 5, and 6) were isolated as known compounds with weak or no cytotoxicity. These compounds were examined for their respective apoptosis- and differentiation-inducing activities toward HL-60 cells by DNA fragmentation and NBT-reducing assays, respectively. Among them, 7alpha-hydroxysandaracopimaric acid (6) was found to have a potent differentiation-inducing activity in a dose-dependent manner at 0.125-2 microg/ml (0.39-6.29 microM), together with apoptosis-inducing activity at concentrations of more than 2.5 microg/ml (7.86 microM). Deoxypodophyllotoxin (4) that exerted cytotoxic and apoptosis-inducing activities at 2 ng/ml (5 nM) did not induce differentiation at the same concentration, and the other diterpenes (1-3 and 5) showed no effect on cell differentiation, even at 5 microg/ml. It was thus demonstrated for the first time that 7alpha-hydroxysandaracopimaric acid was an effective differentiation-inducing compound toward HL-60 cells.

A new flavone xyloside and two new flavan-3-ol glucosides from Juniperus communis var. depressa.

A new flavone xyloside, 1, and two new flavan-3-ol glucosides, 3 and 4, were isolated together with three known flavones, 2, 11, and 12, five known flavans, 5-9, and a known dihydrochalcone, 10, from the stems and leaves of Juniperus communis var. depressa (Cupressaceae) collected in Oregon, U.S.A., and their structures were determined on the basis of spectral evidence. A novel flavone nucleus such as that in 1 is seldom found in nature today, and new methylcatechin glucosides 3 and 4 are also rare in nature. In addition, we investigated the inhibitory activity of individual components, i.e., 8-11, and others, that were abundantly isolated from the same plant material for the Maillard reaction.

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.

Unusual cyclolanostanes from leaves of Pandanus boninensis.

Two unusual triterpenoids, (24S)-24-methyl-25,32-cyclo-5alpha-lanosta-9(11)-en-3beta-ol and (24S)-24-methyl-25,32-cyclo-cycloartane-3beta-ol, were isolated from leaves of Pandanus boninensis along with known triterpenoids and lignans. Their structures were established on the basis of spectroscopic methods and X-ray analysis.

Four new trimeric stilbene glucosides from Welwitschia mirabilis.

Four new trimeric stilbene glucosides, mirabilosides C-F (1-4) were isolated from MeOH extract of stem and root of Welwitschia mirabilis (Welwitschiaceae) along with three known stilbenoids, resveratrol (5), gnemonoside B (6), and gnetin G (7). The structures of these compounds were elucidated by spectroscopic methods.