Background
The concept of frailty becomes important for patients who undergo surgery in this recent aging society. The aim of this study is to investigate the frailty as a prognostic factor in ...elderly patients with hepatocellular carcinoma (HCC) who underwent hepatectomy.
Patients and Methods
A total of 92 patients over 75 years old who underwent hepatectomy were enrolled in this study. Frailty was defined as clinical frailty scale (CFS) ≥ 4. Patients were divided into two groups, i.e., frailty group (
n
= 21) and no-frailty group (
n
= 71), and clinicopathological features were compared between them.
Results
The frailty group showed significant higher PIVKA-II level and larger tumor diameter (
p
< 0.05). CRP level and modified Glasgow prognostic score were significantly higher in the frailty group (
p
< 0.05). The frailty group showed higher rate of postoperative complications of Clavien–Dindo III (
p
= 0.06) and longer postoperative stay (
p
= 0.08). Cancer-specific, overall, and disease-free survival rates were significantly worse in the frailty group (
p
< 0.05). Frailty was detected as an independent prognostic factor on multivariate analysis of cancer-specific survival.
Conclusion
Frailty can estimate the prognosis of HCC patients who underwent hepatectomy.
Background
We evaluated apparent diffusion coefficient (ADC) of diffusion‐weighted image MRI as a prognostic factor for mass‐forming intrahepatic cholangiocarcinoma (IHCC).
Methods
We enrolled 26 ...patients who had undergone hepatic resections for mass‐forming‐type IHCC in this study, and calculated their mean ADC, using diffusion‐weighted image MRI (b: 0, 20, 800 seconds/mm2; 1.5 T MRI). Patients were divided into the ADCHigh and the ADCLow groups at the median ADC value (n = 13 for both). We also immunohistochemically evaluated hypoxia‐inducible factor (HIF)‐1α in tumor tissue.
Results
Median age in the ADCLow was older (P = .03), and showed significant higher rate of scirrhous tumor (P = .02). The 5‐year overall survival rate in the ADCLow group was significantly worse than in the ADCHigh group (P = .04). In multivariate analysis, hilar tumor, portal vein invasion and low ADC were independent prognostic factors (P < .05). The ADCLow group also had a higher rate of high HIF‐1α expression than the ADCHigh group (P < .05). Representative case of ADCLow group showed rich stroma and high HIF‐1α expression.
Conclusions
The ADC values in MRIs can predict IHCC prognosis, and correlated with stromal density and HIF‐1α expression.
Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24
...-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative
. Optimization of 4-arylpyridine derivatives led us to identify
((4-benzyl-4-hydroxypiperidin-1-yl)(2,4'-bipyridin-3-yl)methanone, IC
= 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice,
resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound
(soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies.
Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that converts cholesterol into 24S-hydroxycholesterol, the primary mechanism of cholesterol catabolism in the brain. The therapeutic ...potential of CH24H activation has been extensively investigated, whereas the effects of CH24H inhibition remain poorly characterized. In this study, the therapeutic potential of CH24H inhibition was investigated using a newly identified small molecule, soticlestat (TAK-935/OV935). The biodistribution and target engagement of soticlestat was assessed in mice. CH24H-knockout mice showed a substantially lower level of soticlestat distribution in the brain than wild-type controls. Furthermore, brain-slice autoradiography studies demonstrated the absence of
Hsoticlestat staining in CH24H-knockout mice compared with wild-type mice, indicating a specificity of soticlestat binding to CH24H. The pharmacodynamic effects of soticlestat were characterized in a transgenic mouse model carrying mutated human amyloid precursor protein and presenilin 1 (APP/PS1-Tg). These mice, with excitatory/inhibitory imbalance and short life-span, yielded a remarkable survival benefit when bred with CH24H-knockout animals. Soticlestat lowered brain 24S-hydroxycholesterol in a dose-dependent manner and substantially reduced premature deaths of APP/PS1-Tg mice at a dose lowering brain 24S-hydroxycholesterol by approximately 50%. Furthermore, microdialysis experiments showed that soticlestat can suppress potassium-evoked extracellular glutamate elevations in the hippocampus. Taken together, these data suggest that soticlestat-mediated inhibition of CH24H may have therapeutic potential for diseases associated with neural hyperexcitation.
Species of the Citrus genus are known as rich sources of phenolic compounds. Peels of Citrus tachibana and Citrus unshiu are used in herbal formulations, sometimes in similar ways. In this study, we ...examined the effects of plant maturity and genetic background on the total phenolic contents and quantities of specific flavonoids in C. tachibana peel. In addition, we compared these values in C. tachibana and C. unshiu peels. The total phenolic contents and the contents of nobiletin, tangeretin, and hesperidin were higher in the extracts of the immature peel than in those of the mature peels of C. tachibana; moreover, the quantities of these compounds were also influenced by the genetic background of C. tachibana. In the extracts of C. unshiu peel, the contents of total phenolics, nobiletin, and tangeretin were lower than those of C. tachibana peel. However, the hesperidin content was higher in extracts of C. unshiu peel than those of C. tachibana peel. This study evaluated the phenolic and flavonoid contents of C. tachibana and C. unshiu in an effort to provide new insights into herbal medicines for further study and utilization.
Cholesterol 24-hydroxylase (CH24H or CYP46A1) is a brain-specific cytochrome P450 enzyme that metabolizes cholesterol into 24
-hydroxycholesterol (24HC) for regulating brain cholesterol homeostasis. ...For the development of a novel and potent CH24H inhibitor, we designed and synthesized 3,4-disubstituted pyridine derivatives using a structure-based drug design approach starting from compounds
(soticlestat) and
(thioperamide). Optimization of this series by focusing on ligand-lipophilicity efficiency value resulted in the discovery of 4-(4-methyl-1-pyrazolyl)pyridine derivative
(IC
= 8.5 nM) as a potent and highly selective CH24H inhibitor. The X-ray crystal structure of CH24H in complex with compound
revealed a unique binding mode. Both blood-brain barrier penetration and reduction of 24HC levels (26% reduction) in the mouse brain were confirmed by oral administration of
at 30 mg/kg, indicating that
is a promising tool for the novel and selective inhibition of CH24H.
Robinia pseudoacacia L. has been widely planted worldwide for a variety of purposes, but it is a nonindigenous species currently invading the central part of Japanese river terraces. To understand ...and control this invasion, we investigated how this species invests nitrogen resources in different functions depending on the leaf location, and how these resources are used in physiological reactions such as photosynthesis. The Tama river terrace was examined in Tokyo, Japan. The leaf nitrogen (N) concentration, chlorophyll (Chl) concentration, Chl a/b ratio, leaf mass per unit area (LMA) and ribulose-1,5-bisphosphate carboxylase oxygenase (RuBisCo) concentration were all significantly lower in shade leaves than in leaves exposed to the sun. Conversely, the net photosynthetic rate in saturated light conditions (Pmax), the net photosynthetic rate under enhanced CO2 concentration and light saturation (Amax), the maximum carboxylation rate of RuBisCo (Vcmax) and the maximum rate of electron transport driving RUBP regeneration (Jmax) were all significantly lower in shade leaves than in leaves exposed to the sun. We also found that RuBisCo/N and Chl/N were significantly less in shade leaves, and values of Jmax/N, Vcmax/N less in shade leaves than in sun leaves, but not significantly. Allocation of nitrogen in leaves to photosynthetic proteins, RuBisCo (NR) was broadly less in shade leaves, and NL (light-harvesting complex: LHC, photosystem I and II: PSI and PSII) and NE (electron transport) were also lower. The N remaining was much greater in shade leaves than in sun leaves. We suggest that N remobilization from RuBisCo is more efficient than remobilization from proteins of NE, and from NL. This study shows that R. pseudoacacia has an enhanced ability to adapt to environmental changes via characteristic changes in N allocation trade-offs and physiological traits in its sun and shade leaves.
The aim of this study was to investigate advantages of the left-handed ultrasonic shears technique in robotic gastrectomy for gastric cancer.
We retrospectively analyzed 67 consecutive gastric cancer ...patients who underwent robotic gastrectomy. Fifty-six patients underwent gastrectomy with the left-handed ultrasonic shears technique (the left hand group), and 11 patients underwent surgery with the conventional approach (the conventional group). Intraoperative and postoperative outcomes were compared between the 2 groups.
Operative blood loss, morbidity, and mortality were similar between the 2 groups. We observed a trend toward a shorter operation time and higher number of retrieved lymph nodes in the left hand group compared with the conventional group. Console time (docking-gastrectomy) in the left hand group was significantly shorter than in the conventional group (192.20 vs. 218.36 min, P<0.05). In robotic distal gastrectomy, both operation time and console time in the left hand group were significantly shorter than in the conventional group (276.10 vs. 354.80 min, 176.43 vs. 209.20 min, P<0.05 for both). The postoperative intra-abdominal infectious complication (Clavien Dindo≥1) rate in the left hand group was significantly lower than that in the conventional group (0% vs. 20%, P<0.05).
Use of the left-handed ultrasonic shears technique is safe and provides a technically superior operative environment with satisfactory postoperative results.
Two kinds of microorganisms, a bacterium (KT-1 strain) and a fungus (KT-2 strain), degrading nylon 4 (polyamide 4), which was easily prepared by the anionic ring-opening polymerization of ...2-pyrrolidone, were isolated from the composted soil with the utilization of enrichment cultures and the culture using nylon 4 as a carbon source. KT-1 and KT-2 strains were identified as neighboring species to
Stenotrophomonas sp. and
Fusarium sp., respectively, by their morphological properties and the nucleotide sequences. These strains were confirmed to grow in the culture medium containing nylon 4 powders as a carbon source. In addition, nylon 4 film was decomposed in both mineral media containing KT-1 and KT-2 strains, respectively, and disappeared within two months. The MALDI TOF-MS analysis of nylon 4 recovered during the biodegradation test suggest that the isolated KT-2 strain recognize the acyllactam or carboxy chain end and degrade them or their neighboring amide bond.
Aims
To propose a comprehensive classification framework for Japanese forest vegetation, an expert system based on a traditional system was developed, using a large‐scale data set covering the whole ...of Japan.
Location
The entire Japanese archipelago.
Methods
A data set of 12,720 vegetation plots from the National Vegetation Survey database was established. Then, an expert system for automatic hierarchical classification was developed, based on the traditional system. The classification effectiveness was verified using fidelity measures, the occurrence of traditional characteristic species, consistency with semi‐supervised K‐means and modified TWINSPAN, and the similarity between each unit. To investigate correspondence to the environmental variables, a detrended correspondence analysis with the “envfit” function was used. Additionally, the occurring taxa were collated and compared with the flora lists of areas surrounding Japan.
Results
The Japanese forest data set was classified into 34 alliances by the expert system, and 14 orders and six classes were distinguished. Most of these units had diagnostic taxa including existing characteristic species and the heatmap of the Bray–Curtis index showed the independence of each unit, and the similarity of the plot groups assigned to the same unit. Out of 34 alliances, clustering with semi‐supervised K‐means supported 21 alliances, and modified TWINSPAN supported 16 alliances. The four classes correspond to the thermal conditions and support the existing concept of vegetation zones. The lower‐level vegetation units correspond to a narrower range of environmental variables than higher‐level units, and species composition varied with limited environmental variables. A floristic composition comparison emphasized the complexity of the species composition of Japanese forests.
Conclusions
This study proposes the first formal Japanese forest classification at the class, order, and alliance levels, reflecting traditional phytosociology systems and based on large‐scale vegetation plot data. Our classification provides an important foundation for the future revision of formal phytosociological systems throughout East Asia.
This study provides the first comprehensive formal classification definition for forest vegetation throughout Japan. Our classification results support the concepts of the traditional phytosociological concepts and emphasize the diversity of the Japanese floristic composition. The relationships between the phytosociological units recognized using the expert system and environmental variables, such as thermal conditions, support existing concepts of the vegetation zones.
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