Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis.

Vitamin D administered pre-diagnostically has been shown to reduce mortality. Emerging evidence suggests a role of post-diagnosis vitamin D supplement intake for survival among cancer patients. Thus, we conducted a meta-analysis to evaluate the relationship. PubMed and Embase were searched for relevant observational cohort studies and randomized trials published through April 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The SRR for post-diagnosis vitamin D supplement use vs. non-use, pooling cohort studies and randomized trials, was 0.87 (95% CI, 0.78-0.98; p = 0.02; I2 = 0%) for overall survival, 0.81 (95% CI, 0.62-1.06; p = 0.12; I2 = 51%) for progression-free survival, 0.86 (95% CI, 0.72-1.03; p = 0.10; I2 = 0%) for cancer-specific survival, and 0.86 (95% CI, 0.64-1.14; p = 0.29; I2 = 0%) for relapse. Albeit not significantly heterogeneous by variables tested, a significant inverse association was limited to cohort studies and supplement use during cancer treatment for overall survival, and to studies with ≤3 years of follow-up for progression-free survival. Post-diagnosis vitamin D supplement use was associated with improved overall survival, but not progression-free or cancer-specific survival or relapse. Our findings require confirmation, as randomized trial evidence was insufficient to establish cause-and-effect relationships.

Prognostic Implications of Chemotherapy-Induced Neutropenia in Stage III Colorectal Cancer.

BACKGROUND: Previous studies have reported chemotherapy-induced neutropenia (CIN) as a prognostic factor in stage IV colorectal cancer (CRC). However, only few reports analyzed the prognostic value of CIN in patients with stage III CRC who received adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). We aimed to investigate the prognostic implications of CIN in patients with stage III CRC who received adjuvant chemotherapy with FOLFOX. MATERIALS AND METHODS: We retrospectively analyzed patients with stage III CRC who received adjuvant chemotherapy with FOLFOX at a tertiary hospital between January 2007 and December 2017. Severe CIN was defined as an absolute neutrophil count of less than 1000/mm3. Three-y disease-free survival (DFS) and overall survival (OS) were analyzed as primary endpoints. RESULTS: Among the 199 patients included in this study, 110 patients (55.3%) experienced severe CIN. There were no significant differences in survival outcomes between the control and CIN groups (control group versus CIN group: 3-y OS, 82.0 % versus 72.7 %; log rank, P = 0.250 and 3-y DFS, 71.9 % versus 62.7; log rank, P = 0.294). Univariate and multivariate analyses revealed that CIN did not affect DFS and OS in patients with stage III CRC who received adjuvant FOLFOX chemotherapy. CONCLUSIONS: Severe CIN occurring during adjuvant FOLFOX chemotherapy did not play a significant role in the prognosis of patients with stage III CRC.

(-)-Gallocatechin gallate from green tea rescues cognitive impairment through restoring hippocampal silent synapses in post-menopausal depression.

Post-menopausal depression (PMD) is a common psychological disorder accompanied by a cognitive deficit, which is caused by a series of uncontrolled emotional disruptions by strong environmental stressors during menopause. To overcome PMD-induced cognitive deficit, Green tea has been suggested as a dietary supplement because of its ameliorating effect on cognitive dysfunction induced by normal aging or neurodegenerative syndromes; however, its clinical use to improve PMD-accompanied cognitive deficit is still limited due to the controversy for the active ingredients and ambiguous mechanism of its action. Here, we developed modified high-temperature-processed green tea extract (HTP-GTE), which showed lower neuronal toxicity than the conventional green tea extract (GTE). We also demonstrated that HTP-GTE administration prevented the development of learned helplessness (LH) in a rat post-menopausal model. Additionally, HTP-GTE improved LH-induced cognitive impairments simultaneously with rescued the long-term synaptic plasticity. This occurred via the restoration of silent synapse formation by increasing the hippocampal BDNF-tyrosine receptor kinase B pathway in the helpless ovariectomized (OVX) rats. Likewise, we also identified that (-)-gallocatechin gallate was the main contributor of the HTP-GTE effect. Our findings suggested that HTP-GTE has a potential as a preventive nutritional supplement to ameliorate cognitive dysfunctions associated with PMD.

Thermochemical conversion of cobalt-loaded spent coffee grounds for production of energy resource and environmental catalyst.

Thermochemical conversion of cobalt (Co)-loaded lignin-rich spent coffee grounds (COSCG) was carried out to find the appropriate pyrolytic conditions (atmospheric gas and pyrolytic time) for syngas production (H2 and CO) and fabricate Co-biochar catalyst (CBC) in one step. The use of CO2 as atmospheric gas and 110-min pyrolytic time was optimal for generation of H2 (∼1.6 mol% in non-isothermal pyrolysis for 50 min) and CO (∼4.7 mol% in isothermal pyrolysis for 60 min) during thermochemical process of COSCG. The physicochemical properties of CBC fabricated using optimized pyrolytic conditions for syngas production were scrutinized using various analytical instruments (FE-SEM, TEM, XRD, and XPS). The characterizations exhibited that the catalyst consisted of metallic Co and surface wrinkled carbon layers. As a case study, the catalytic capability of CBC was tested by reducing p-nitrophenol (PNP), and the reaction kinetics of PNP in the presence of CBC was measured from 0.04 to 0.12 s-1.

Promotion of Glucose Uptake in C2C12 Myotubes by Cereal Flavone Tricin and Its Underlying Molecular Mechanism.

The effect of tricin, a methylated flavone widely distributed in cereals, on glucose uptake and the underlying molecular mechanism was investigated using C2C12 myotubes. Tricin significantly increased glucose uptake in C2C12 myotubes, regardless of the absence (1.4-fold at 20 µM) or presence (1.6-fold at 20 µM) of insulin. The GLUT4 expression on the plasma membrane was increased 1.6-fold after tricin treatment (20 µM) in the absence of insulin. Tricin treatment significantly activated the insulin-dependent cell signaling pathway, including the activation of insulin receptor substrate-1 (IRS1), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and AKT substrate of 160 kDa (AS160). The oral administration of tricin (64 and 160 mg kg-1 of body weight day-1) also significantly lowered blood glucose levels in glucose-loaded C57BL/6 mice (p < 0.05). These results suggest that tricin has great potential to be used as a functional agent for glycemic control.

Hyaluronic acid-supported combination of water insoluble immunostimulatory compounds for anti-cancer immunotherapy.

A novel powder-form combination adjuvant system containing two immunostimulatory compounds was firstly developed and evaluated as a therapeutic intervention for cancer immunotherapy. With the help of hyaluronic acid (HA), water insoluble monophosphoryl lipid A (MPL), QS21 and imiquimod (R837), could be easily dispersed in aqueous solution and lyophilized as powder-form, which have an advantage in room-temperature storage stability compared with those conventional liquid formulation that requires cold storage. Two kinds of HA-based combination vaccine adjuvants (HA/MPL/QS21, HMQ and HA/MPL/R837, HMR) contributed to the increase of both humoral and cellular immunity, which is very important for efficient cancer immunotherapy. Through the challenge experiments in EG7-OVA (mouse lymphoma-expressing OVA) tumor-bearing mice model, we found out that the immunostimulatory effects of HMQ and HMR were successful in the inhibition of tumor proliferation. Taken together, both HA-based powder-form combination adjuvant systems are expected to be used as potent prophylactic and therapeutic cancer vaccine.

NanoESI-MS-based lipidomics to discriminate between cultivars, cultivation ages, and parts of Panax ginseng.

Korean ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs used in Asia, including Korea and China. In the present study lipid profiling of two officially registered cultivars (P. ginseng 'Chunpoong' and P. ginseng 'Yunpoong') was performed at different cultivation ages (5 and 6 years) and on different parts (tap roots, lateral roots, and rhizomes) using nano-electrospray ionization-mass spectrometry (nanoESI-MS). In total, 30 compounds including galactolipids, phospholipids, triacylglycerols, and ginsenosides were identified. Among them, triacylglycerol 54:6 (18:2/18:2/18:2), phosphatidylglycerol 34:3 (16:0/18:3), monogalactosyldiacylglycerol 36:4 (18:2/18:2), phosphatidic acid species 36:4 (18:2/18:2), and 34:1 (16:0/18:1) were selected as biomarkers to discriminate cultivars, cultivation ages, and parts. In addition, an unknown P. ginseng sample was successfully predicted by applying validated partial least squares projection to latent structures regression models. This is the first study regarding the identification of intact lipid species from P. ginseng and to predict cultivars, cultivation ages, and parts of P. ginseng using nanoESI-MS-based lipidomic profiling with a multivariate statistical analysis.

In vitro anti-inflammatory components isolated from the carnivorous plant Nepenthes mirabilis (Lour.) Rafarin.

CONTEXT: Nepenthes mirabilis (Lour.) Rafarin (Nepenthaceae) is a carnivorous plant used as a folk medicine in the treatment of jaundice, hepatitis, gastric ulcers, ureteral stones, diarrhea, diabetes, and high blood pressure. Neither the phytochemical content nor biological activities of N. mirabilis have been reported. OBJECTIVE: The anti-inflammatory activity from the N. mirabilis methanolic extract led to the isolation of compounds (1-26). MATERIALS AND METHODS: Chromatographic methods were used to isolate compounds from the methanol extract of N. mirabilis branches and leaves. The anti-inflammatory activity of these isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) using ELISA. Primary BMDCs were used to examine the production of pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-α, at concentrations of 0.1, 0.2, and 1.0 µM) as compared with a positive control, SB203580 (1.0 µM). MTT assays showed that isolated compounds (1-26) did not exhibit significant cytotoxicity at concentrations up to 20.0 µM. RESULTS: Compound 9 showed potent inhibition of IL-12 p40, IL-6, and TNF-α production (IC50 = 0.17 ± 0.02, 0.46 ± 0.01, and 8.28 ± 0.21 µM, respectively). Compound 4 showed potent inhibition of IL-12 p40 and IL-6 production (IC50 = 1.17 ± 0.01 and 2.15 ± 0.04 µM). In addition, IL-12 p40 inhibition by naphthalene derivatives (1-7, 9, and 10), phenolic compounds (11-15), lupeone (18), and flavonoids (22, 25, and 26) was more potent than with the positive control. The isolated compounds exhibited little and/or no inhibitory effects on TNF-α production in LPS-stimulated BMDCs. DISCUSSION AND CONCLUSION: Taken together, these data suggest that the isolated components have significant inhibitory effects on pro-inflammatory cytokine production and warrant further study concerning their potential medicinal use.

Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics.

Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity.

Chemical constituents from Kandelia candel with their inhibitory effects on pro-inflammatory cytokines production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs).

Chemical investigation of Kandelia candel resulted in the isolation of 19 compounds (1-19), including one new sesquiterpene glycoside, kandelside (1), three megastigman glycoside compounds (7-9), 16 known phenolic compounds (2-6 and 10-19). Structures of the isolated compounds were elucidated based on spectral data comparison with reported values. Isolated compounds were also evaluated for their inhibitory effects on the production of pro-inflammatory cytokines interleukin (IL)-12 p40, IL-6, and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among these compounds, compound 9 exhibited strong inhibitory activity against IL-6 production (IC50=0.07 ± 0.05 µM) and moderate inhibitory activity against TNF-α production (IC50=49.86 ± 1.02 µM), but exhibited no activity on IL-12 p40 production. Compounds 5 and 6 significantly inhibited IL-12 p40, IL-6, and TNF-α production with IC50 values of 11.68 ± 0.38, 44.52 ± 1.08, and 28.73 ± 0.96 µM, respectively.

Flavonoids from Astragalus membranaceus and their inhibitory effects on LPS-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells.

Radix Astragali (Astragalus membranaceus) is an important traditional Chinese medicine that is widely used as a tonic to enhance the body's natural defense mechanisms. In this phytochemical study, 12 flavonoids, isoliquiritigenin (1), liquiritigenin (2), calycosin (3), calycosin 7-O-ß-D-glucoside (4), formononetin (5), formononetin 7-O-ß-D-glucoside (6), daidzein (7), daidzein 7-O-ß-D-glucoside (8), methylnissolin (9), methylnissolin 3-O-ß-D-glucoside (10), isomucronulatol (11), and isomucronulatol 7-O-ß-D-glucoside (12), were isolated from the roots of A. membranaceus. Their structures were elucidated by comparing spectroscopic data with reported values. The effects of the isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells were investigated. Compounds 1 and 2 exhibited significant inhibitory effects on LPS-induced IL-6 and IL-12 p40 production, with IC50 values ranging from 2.7 to 6.1 µM. Compound 1 also showed a moderate inhibitory effect on LPS-stimulated production of TNF-α with an IC50 value of 20.1 µM. Further studies of the potential anti-inflammatory effects and benefits of flavonoids from A. membranaceus are warranted.

Anti-inflammatory and antioxidant activities of phenolic compounds from Desmodium caudatum leaves and stems.

Four flavanonols (1-4), one xanthone (5), and three flavonoid glycosides (6-8), were isolated from the leaves and stems of Desmodium caudatum. Their structures were elucidated by comparing spectroscopic data with reported values. The anti-inflammatory activity of the isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among them, compounds 1 and 2 exhibited inhibitory effects on LPS-induced IL-6, IL-12 p40, and TNF-α production with IC50 values ranging from 6.0 to 29.4 µM. Compound 5 exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species scavenging activity in human HaCaT keratinocytes. These results warrant further studies of the potential anti-inflammatory and antioxidant benefits of compounds from D. caudatum.

Apo-9'-fucoxanthinone, isolated from Sargassum muticum, inhibits CpG-induced inflammatory response by attenuating the mitogen-activated protein kinase pathway.

Sargassum muticum (S. muticum) is a brown edible alga and widely distributed in Korea. This report was designed to evaluate the anti-inflammatory properties of apo-9'-fucoxanthinone (APO-9') isolated from S. muticum on pro-inflammatory cytokine production. S. muticum extract (SME) exhibited significant inhibitory effects on pro-inflammatory cytokine production in bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs). APO-9' pre-treatment in the CpG DNA-stimulated BMDMs and BMDCs showed a strong dose-dependent inhibitory effect on interleukin (IL)-12 p40, IL-6 and tumor necrosis factor (TNF)-α production with IC50 values ranging from 5.31 to 13.79. It exhibited a strong inhibitory effect on the phosphorylation of ERK1/2 and on activator protein (AP)-1 reporter activity. APO-9' pre-treatment exhibited significant inhibition of CpG DNA-induced production of inducible nitric oxide synthase. Taken together, these data suggest that SME and APO-9' have a significant anti-inflammatory property and warrant further studies concerning the potentials of SME and APO-9' for medicinal use.

Metabolic profiling and predicting the free radical scavenging activity of guava (Psidium guajava L.) leaves according to harvest time by 1H-nuclear magnetic resonance spectroscopy.

Guava leaves were classified and the free radical scavenging activity (FRSA) evaluated according to different harvest times by using the (1)H-NMR-based metabolomic technique. A principal component analysis (PCA) of (1)H-NMR data from the guava leaves provided clear clusters according to the harvesting time. A partial least squares (PLS) analysis indicated a correlation between the metabolic profile and FRSA. FRSA levels of the guava leaves harvested during May and August were high, and those leaves contained higher amounts of 3-hydroxybutyric acid, acetic acid, glutamic acid, asparagine, citric acid, malonic acid, trans-aconitic acid, ascorbic acid, maleic acid, cis-aconitic acid, epicatechin, protocatechuic acid, and xanthine than the leaves harvested during October and December. Epicatechin and protocatechuic acid among those compounds seem to have enhanced FRSA of the guava leaf samples harvested in May and August. A PLS regression model was established to predict guava leaf FRSA at different harvesting times by using a (1)H-NMR data set. The predictability of the PLS model was then tested by internal and external validation. The results of this study indicate that (1)H-NMR-based metabolomic data could usefully characterize guava leaves according to their time of harvesting.

Rapid sequential separation of essential oil compounds using continuous heart-cut multi-dimensional gas chromatography-mass spectrometry.

A method for separation and identification of peaks in essential oil samples based on rapid repetitive heart-cutting using multidimensional gas chromatography (MDGC)-mass spectrometry (MS) coupled with a cryotrapping interface is described. Lavender essential oil is analyzed by employing repetitive heart-cut intervals of 1.00 and 1.50 min, achieved in a parallel MDGC-MS/GC-FID experiment. The number of peaks that were detected in 1D GC operation above a given response threshold more than tripled when MDGC-MS employing the cryotrapping module method was used. In addition, MDGC-MS enabled detection of peaks that were not individually evident in 1D GC-MS, owing to effective deconvolution in time of previously overlapped peaks in 1D GC. Thus separation using the cryomodulation approach, without recourse to using deconvolution software, was possible. Peaks widths decreased by about 5-7-fold with the described method, peak capacity increased from about 9 per min to 60 per min, and greater sensitivity results. Repeatability of retention times for replicate analyses in the multidimensional mode was better than 0.02% RSD. The present study suggests that the described heart-cutting technique using MDGC-MS can be used for general improvement in separation and identification of volatile compounds.

(1)H-NMR-based discrimination of thermal and vinegar treated ginseng roots.

To investigate the changes in nonvolatile metabolites of thermal and/or vinegar treated ginseng (TVG), samples prepared using various treatment conditions were analyzed using an (1)H-NMR-based metabolomics technique. The processing conditions of the ginseng in this study were 100, 140, and 180 degrees C with and without vinegar and the duration of exposure to each temperature was 10, 30, and 50 min, respectively. There was a clear separation in the score plots among various treatment conditions. Major compounds contributing to the separation of 50% methanol extracts of TVG with various process conditions were valine, lactate, alanine, arginine, glucose, fructose, and sucrose. As temperature increased, valine, arginine, glucose, fructose, and sucrose concentrations decreased, whereas lactate, glucose, and fructose increased in the vinegar-treated samples compared to non-vinegar-treated samples. The present study suggests the usefulness of an (1)H-NMR-based metabolomics approach to discriminate TVG samples, subjected to different processing conditions.

Classification and prediction of free-radical scavenging activities of dangyuja (Citrus grandis Osbeck) fruit extracts using (1)H NMR spectroscopy and multivariate statistical analysis.

Different parts of dangyuja (Citrus grandis Osbeck) fruits at different maturation stages were classified using a (1)H NMR-based metabolomic technique. Principal components analysis allowed the clear separation of fractions extracted with 50% methanol of different parts of dangyuja fruits at different maturation stages by combining principal components PC1 and PC2, which together accounted for 80.4% of the variance. A loading-plot analysis revealed that sucrose, glucose, oxaloacetic acid and citric acid were dominant in mature flesh, while naringin, tyramine, proline and alanine were dominant in immature fruit samples. Projections to latent structures using a partial least squares (PLS) model were used to predict the free-radical scavenging activities (FRSA) of dangyuja fruit extracts based on their (1)H NMR spectra. The present study suggests the usefulness of combining (1)H NMR spectroscopy with multivariate statistical analysis for discriminating dangyuja fruit samples, and predicting the FRSA of different parts of dangyuja fruit samples at different stages of maturation.

Microbial metabolites of 8-prenylnaringenin, an estrogenic prenylflavanone.

Microbial metabolism studies of the phyto-estrogen (+/-)-8-prenylnaringenin (8-PN) (1) has led to the isolation of three pairs of metabolites (2-4). The structures of these compounds were identified as 5,4'-dihydroxy-7,8-[2-(1-hydroxy-1-methylethyl)-2,3-dihydrofurano]flavanones (2), 8-prenylnaringenin 7-O-beta-D-glucopyranosides (3), and 8-prenylnaringenin 7-O-beta-D-(6'''-O-alpha-hydroxypropionyl)-glucopyranosides (4) on the basis of the spectroscopic analysis.