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1.
Kidney Res Clin Pract ; 43(2): 177-185, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37098678

ABSTRACT

BACKGROUND: In addition to improving the serum vitamin D balance, narrowband ultraviolet B (NB-UVB) phototherapy can effectively treat chronic kidney disease-associated pruritus (CKD-aP). We investigated the degree of CKD-aP amelioration according to changes in the serum vitamin D level after NB-UVB phototherapy. METHODS: This was a before-after clinical study in patients with refractory CKD-aP on hemodialysis. NB-UVB phototherapy was administered thrice weekly for 12 weeks. The response of CKD-aP to NB-UVB phototherapy was assessed as the change in pruritus intensity over time. A rapid response was defined as a reduction in the visual analog scale (VAS) score of ≥50% within the first 6 weeks of NB-UVB phototherapy. RESULTS: We included 34 patients in this study. Although serum 25-hydroxy vitamin D [25(OH)D] concentrations increased significantly, by a median of 17.4 ng/mL, after the phototherapy course, other serologic parameters did not change. NB-UVB phototherapy reduced the VAS score for pruritus intensity over time significantly more in patients with Δ25(OH)D of >17.4 ng/mL than in patients with Δ25(OH)D of ≤17.4 ng/mL (p = 0.001). Ten patients were rapid responders. Multivariate logistic regression analysis showed that Δ25(OH)D was independently associated with rapid response (odds ratio, 1.29; 95% confidence interval, 1.02-1.63; p = 0.04). CONCLUSION: The effect of NB-UVB phototherapy on patients with CKD-aP correlated with their increase in serum vitamin D levels. Further well-designed clinical and experimental studies are needed to clarify the relationship between NB-UVB phototherapy and serum vitamin D levels in patients with CKD-aP.

2.
Clin Nutr Res ; 12(2): 126-137, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37214779

ABSTRACT

Hemodialysis (HD) patients face a common problem of malnutrition due to poor appetite. This study aims to verify the appetite alteration model for malnutrition in HD patients through quantitative data and the International Classification of Functioning, Disability, and Health (ICF) framework. This study uses the Mixed Method-Grounded Theory (MM-GT) method to explore various factors and processes affecting malnutrition in HD patients, create a suitable treatment model, and validate it systematically by combining qualitative and quantitative data and procedures. The demographics and medical histories of 14 patients were collected. Based on the theory, the research design is based on expansion and confirmation sequence. The usefulness and cut-off points of the creatinine index (CI) guidelines for malnutrition in HD patients were linked to significant categories of GT and the domain of ICF. The retrospective CIs for 3 months revealed patients with 3 different levels of appetite status at nutrition assessment and 2 levels of uremic removal. In the same way, different levels of dry mouth, functional support, self-efficacy, and self-management were analyzed. Poor appetite, degree of dryness, and degree of taste change negatively affected CI, while self-management, uremic removal, functional support, and self-efficacy positively affected CI. This study identified and validated the essential components of appetite alteration in HD patients. These MM-GT methods can guide the selection of outcome measurements and facilitate the perspective of a holistic approach to self-management and intervention.

3.
Plants (Basel) ; 12(5)2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36904006

ABSTRACT

Inflammation is an indispensable part of the human body's self-defense mechanism against external stimuli. The interactions between Toll-like receptors and microbial components trigger the innate immune system via NF-κB signaling, which regulates the overall cell signaling including inflammatory responses and immune modulations. The anti-inflammatory effects of Hyptis obtusiflora C. Presl ex Benth, which has been used as a home remedy for gastrointestinal disorders and skin disease in rural areas of Latin America, have not yet been studied. Here, we investigate the medicinal properties of Hyptis obtusiflora C. Presl ex Benth methanol extract (Ho-ME) for inflammatory response suppression. Nitric oxide secretion in RAW264.7 cells triggered by TLR2, 3, or 4 agonists was reduced by Ho-ME. Reduction of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and interleukin (IL)-1b mRNA expression was observed. Decreased transcriptional activity in TRIF- and MyD88-overexpressing HEK293T cells was detected with a luciferase assay. Additionally, serially downregulated phosphorylation of kinase in the NF-κB pathway by Ho-ME was discovered in lipopolysaccharide-treated RAW264.7 cells. Together with the overexpression of its constructs, AKT was identified as a target protein of Ho-ME, and its binding domains were reaffirmed. Moreover, Ho-ME exerted gastroprotective effects in an acute gastritis mouse model generated by the administration of HCl and EtOH. In conclusion, Ho-ME downregulates inflammation via AKT targeting in the NF-κB pathway, and the combined results support Hyptis obtusiflora as a new candidate anti-inflammatory drug.

4.
J Ethnopharmacol ; 305: 116015, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-36563890

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Family: Leguminosae), an herbal plant, has been used in East Asian home remedies for centuries for treating ulcers, skin burns, fevers, and inflammatory disorders. In addition, the dried root of S. flavescens was also applied for antipyretic, analgesic, antihelmintic, and stomachic uses. AIM OF STUDY: Nonetheless, how this plant can show various pharmacological activities including anti-inflammatory responses was not fully elucidated. In this study, therefore, we aimed to investigate the curative effects of S. flavescens on inflammation and its molecular mechanism. MATERIALS AND METHODS: For reaching this aim, various in vitro and in vivo experimental models with LPS-treated RAW264.7 cells, HCl/EtOH-induced gastric ulcer, and LPS-triggered lung injury conditions were employed and anti-inflammatory activity of S. flavescens methanol extract (Sf-ME) was also tested. Fingerprinting profile of Sf-ME was identified via LC-MS analysis. Its anti-inflammatory molecular mechanism was also examined by immunoblotting analysis. RESULTS: Nitric oxide production and mRNA expression levels of iNOS, COX-2, IL-1ß, and TNF-α were decreased. Additionally, phosphorylation of Src in the signaling cascade was decreased, and activities of the transcriptional factor NF-κB were reduced as determined by a luciferase reporter assay. Moreover, in vivo, gastritis and lung injury lesions were attenuated by Sf-ME. CONCLUSION: Taken together, these findings suggest that Sf-ME could be a potential anti-inflammatory therapeutic agent via suppression of Src kinase activity and regulation of IL-1ß secretion.


Subject(s)
Lung Injury , Methanol , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Lipopolysaccharides/pharmacology , Lung Injury/drug therapy , NF-kappa B/metabolism , Nitric Oxide/metabolism , Phosphorylation , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , RAW 264.7 Cells , Sophora flavescens , src-Family Kinases/metabolism
5.
Plants (Basel) ; 11(24)2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36559672

ABSTRACT

Many species in the genus Guettarda are known to exert anti-inflammatory effects and are used as traditional medicinal plants to treat various inflammatory symptoms. However, no studies on the inflammatory activities of Guettarda crispiflora Vahl have been reported. The aim of the study was to investigate in vitro and in vivo the anti-inflammatory effects of a methanol extract of Guettarda crispiflora Vahl (Gc-ME). To determine the anti-inflammatory activity of Gc-ME, lipopolysaccharide (LPS)-, poly(I:C)-, or Pam3CSK4-treated RAW264.7 cells, HCl/EtOH- and LPS-treated mice were employed for in vitro and in vivo tests. LPS-induced nitric oxide production in RAW264.7 cells was determined by Griess assays and cytokine gene expression in LPS-activated RAW264.7 cells, confirmed by RT- and real-time PCR. Transcriptional activation was evaluated by luciferase reporter gene assay. Target protein validation was assessed by Western blot analysis and cellular thermal shift assays (CETSA) with LPS-treated RAW264.7 and gene-transfected HEK293 cells. Using both a HCl/EtOH-induced gastritis model and an LPS-induced lung injury model, inflammatory states were checked by scoring or evaluating gastric lesions, lung edema, and lung histology. Phytochemical fingerprinting of Gc-ME was observed by using liquid chromatography-mass spectrometry. Nitric oxide production induced by LPS and Pam3CSK4 in RAW264.7 cells was revealed to be reduced by Gc-ME. The LPS-induced upregulation of iNOS, COX-2, IL-6, and IL-1ß was also suppressed by Gc-ME treatment. Gc-ME downregulated the promotor activities of AP-1 and NF-κB triggered by MyD88- and TRIF induction. Upstream signaling proteins for NF-κB activation, namely, p-p50, p-p65, p-IκBα, and p-Src were all downregulated by Ch-EE. Moreover, Src was revealed to be directly targeted by Gc-ME. This extract, orally treated strongly, attenuated the inflammatory symptoms in HCl/EtOH-treated stomachs and LPS-treated lungs. Therefore, these results strongly imply that Guettarda crispiflora can be developed as a promising anti-inflammatory remedy with Src-suppressive properties.

6.
Molecules ; 26(20)2021 Oct 16.
Article in English | MEDLINE | ID: mdl-34684856

ABSTRACT

An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.


Subject(s)
Acute Lung Injury/drug therapy , Gastritis/drug therapy , NF-kappa B/metabolism , Pinus/chemistry , Plant Extracts/pharmacology , Signal Transduction/drug effects , Transcription Factor AP-1/metabolism , Acute Lung Injury/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Cell Line , Cyclooxygenase 2/metabolism , Ethanol/chemistry , Gastritis/metabolism , HEK293 Cells , Humans , Interleukin-6/metabolism , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , RAW 264.7 Cells , RNA, Messenger/metabolism
7.
Molecules ; 26(19)2021 Oct 08.
Article in English | MEDLINE | ID: mdl-34641616

ABSTRACT

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.


Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/administration & dosage , Cissus/chemistry , Ethanol/adverse effects , Gastritis/drug therapy , Hydrochloric Acid/adverse effects , Lipopolysaccharides/adverse effects , Macrophages/cytology , Polyphenols/administration & dosage , Acute Lung Injury/chemically induced , Acute Lung Injury/genetics , Administration, Oral , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cytokines/genetics , Disease Models, Animal , Dose-Response Relationship, Drug , Gastritis/chemically induced , Gastritis/genetics , Gene Expression Regulation/drug effects , HEK293 Cells , Humans , MAP Kinase Kinase Kinases/genetics , MAP Kinase Kinase Kinases/metabolism , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Plant Extracts/chemistry , Polyphenols/chemistry , RAW 264.7 Cells , Signal Transduction/drug effects , Treatment Outcome , src-Family Kinases/genetics
8.
Metabolites ; 11(9)2021 Aug 30.
Article in English | MEDLINE | ID: mdl-34564401

ABSTRACT

Many indigenous Korean plants have been used in medicinal preparations and health-promoting foods. These plant species contain beneficial metabolites with various bioactivities, such as antioxidant and anti-inflammatory activities. Herein, we suggest a new screening strategy using metabolomics to explore the bioactive compounds in 50 Korean plants. Secondary metabolites were analyzed using UHPLC-LTQ-Orbitrap-MS/MS. The plant extracts were subjected to antioxidant and anti-inflammatory assays. We identified metabolites that contributed to bioactivities according to the results of bioassays and multivariate analyses. Using Pearson's correlation, phenolics (e.g., casuarictin, 3-O-methylellagic acid) showed positive correlation with antioxidant activity, while biflavonoids (e.g., amentoflavone, rosbustaflavone) were correlated with nitric oxide (NO) inhibition activity. To compensate for the limitation of this new strategy, we further validated these by investigating three parts (branches, fruits, leaves) of Platycladus orientalis which showed high activities on both bioassays. Unlike the above observation, we identified significantly different metabolites from different parts, which was not the results of bioassays. In these validation steps, interestingly, biflavonoids (e.g., robustaflavone, sciadopitysin) contributed to both activities in P. orientalis. The findings of this work suggest that new strategy could be more beneficial in the identification of bioactive plant species as well as that of their corresponding bioactive compounds that impart the bioactivity.

9.
Am J Chin Med ; 49(6): 1493-1514, 2021.
Article in English | MEDLINE | ID: mdl-34247561

ABSTRACT

Muscle atrophy, or loss of skeletal muscle, is caused by aging, malnutrition, immobility through injury, or diseases such as cancer. Chamomile (Matricaria chamomilla L.) contains various active components, including flavonoids, sesquiterpenes, polyacetylenes, and coumarins, and is used in various herbal medicines in the European Pharmacopoeia. In this study, we investigated the effects of ethanol extract of chamomile [Formula: see text](MC) on muscle wasting and its mechanism of action. Mice with dexamethasone (DEX)-induced muscle atrophy were orally administered MC (100, 200, and 300 mg/kg) for 4 weeks. Micro-computed tomography analysis showed that MC (200 and 300 mg/kg) significantly recovered DEX-induced loss of muscle volume, density, and weight and MC-treated DEX-induced mice also showed increased moving distance and grip strength. MC suppressed the mRNA level of muscle RING finger 1 (MuRF1) while increasing the expression of mitochondrial transcription factor A (TFAM), MyoD, and Myogenin-1. We found 25 peaks in MC samples through HPLC analysis and identified 6 peaks by comparison with a profile of standard compounds: chlorogenic acid (CGA), luteolin-7-O-glucoside (L7G), patulitrin, apigenin-7-O-glucoside (A7G), herniarin, and (E)-tonghaosu. Of these components, the gene expression of MyoD was significantly augmented by patulitrin, herniarin, CGA, and L7G in C2C12 cells, while Myogenin-1 gene expression was increased by A7G, patulitrin, herniarin, CGA, and L7G. Moreover, TFAM gene expression and phosphorylation of AKT were increased by all six ingredients. Based on our results, we suggest MC for use as a supplement or remedy for muscle wasting, including cachexia and sarcopenia.


Subject(s)
Chamomile , Mitochondria/drug effects , Muscle Development/drug effects , Muscular Atrophy/drug therapy , Plant Extracts/pharmacology , Animals , Cell Line , Dexamethasone , Disease Models, Animal , Male , Mice , Republic of Korea , X-Ray Microtomography
10.
Front Immunol ; 12: 813748, 2021.
Article in English | MEDLINE | ID: mdl-35095910

ABSTRACT

So far, a number of acupuncture studies have shown anti-inflammatory effects of acupuncture treatment, mostly known at specific point ST36. However, there is no literature that oversaw the inflammation-regulatory effects of acupuncture in each tissue. Therefore, we investigated how acupuncture at specific acupoint ST36 regulates inflammation and its underlying mechanisms. We searched literatures on PubMed until July 2021 using the keywords "animal, acupuncture, ST36, inflammation, immune," and 292 literatures were searched. We ultimately selected 69 studies to determine the anti-inflammatory actions of acupuncture at ST36 and classified the changes of inflammatory mediators according to target regions. Forty-three studies were included in body fluids, 27 studies in the digestive system, 17 studies in the nervous system, and 30 studies in other tissues or organs. In this review, we found that acupuncture at ST36 has clinical benefits in relieving inflammation through several mechanisms such as vagus nerve activation, toll-like receptor 4 (TLR4)/NF-κB signaling, macrophage polarization, mitogen-activated protein kinase (MAPK) signaling pathway, and cholinergic anti-inflammatory pathway. We expect that these data will inform further studies related to ST36 acupuncture on inflammation.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Acupuncture , Inflammation/therapy , Acupuncture/methods , Acupuncture Therapy/methods , Animals , Biomarkers , Disease Models, Animal , Gene Expression Regulation , Immunomodulation , Inflammation/diagnosis , Inflammation/etiology , Inflammation/metabolism , Inflammation Mediators , Neuroimmunomodulation , Signal Transduction , Treatment Outcome
11.
Molecules ; 25(20)2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33050143

ABSTRACT

Muscle atrophy is an abnormal condition characterized by loss of skeletal muscle mass and function and is primarily caused by injury, malnutrition, various diseases, and aging. Leaf of lotus (Nelumbo nucifera Gaertn), which has been used for medicinal purposes, contains various active ingredients, including polyphenols, and is reported to exert an antioxidant effect. In this study, we investigated the effect of water extract of lotus leaf (LL) on muscle atrophy and the underlying molecular mechanisms of action. Amounts of 100, 200, or 300 mg/kg/day LL were administered to dexamethasone (DEX)-induced muscle atrophy mice for 4 weeks. Micro-computed tomography (CT) analysis revealed that the intake of LL significantly increased calf muscle volume, surface area, and density in DEX-induced muscle atrophy mice. Administration of LL recovered moving distance, grip strength, ATP production, and body weight, which were decreased by DEX. In addition, muscle damage caused by DEX was also improved by LL. LL reduced the protein catabolic pathway by suppressing gene expression of muscle atrophy F-Box (MAFbx; atrogin-1), muscle RING finger 1 (MuRF1), and forkhead box O (FoxO)3a, as well as phosphorylation of AMP-activated kinase (AMPK). The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. The HPLC analysis and pharmacological test revealed that quercetin 3-O-beta-glucuronide (Q3G) is a major active component in LL. Thus, Q3G decreased the gene expression of atrogin-1 and MuRF1 and phosphorylation of AMPK. This compound also increased phosphorylation levels of mTOR and its upstream enzyme AKT in DEX-treated C2C12 cells. We identified that LL improves muscle wasting through regulation of muscle protein metabolism in DEX-induced muscle atrophy mice. Q3G is predicted to be one of the major active phenolic components in LL. Therefore, we propose LL as a supplement or therapeutic agent to prevent or treat muscle wasting, such as sarcopenia.


Subject(s)
Dexamethasone/toxicity , Lotus/chemistry , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscular Atrophy/drug therapy , Muscular Atrophy/metabolism , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Water/chemistry , Animals , Blotting, Western , Cell Line , Chromatography, High Pressure Liquid , Male , Mice , Plant Extracts/chemistry , Real-Time Polymerase Chain Reaction , X-Ray Microtomography
12.
Sci Rep ; 9(1): 12740, 2019 09 04.
Article in English | MEDLINE | ID: mdl-31484954

ABSTRACT

The increasing prevalence of cholesterol gallstone disease places an economic burden on the healthcare system. To identify novel therapeutics, we assessed the effects of n-3 polyunsaturated fatty acids (PUFA) in combination with UDCA in a mouse model of cholesterol gallstones. Gallstone dissolution, gallbladder wall thickness, mucin gene expression in the gallbladder, and levels of phospholipids, cholesterol, and bile acids in bile and serum were analysed. RNA was extracted from the liver for mRNA sequencing and gene expression profiling. Combination treatment resulted in greater gallstone dissolution compared with the control group, and PUFA and combination treatments reduced the thickness of the gallbladder wall. Expression levels of mucin genes were significantly lower in the UDCA, PUFA, and combination groups. Transcriptome analyses revealed that combination treatment modulated hepatic lipid metabolism. The PUFA and combination groups showed elevated bile phospholipid and bile acid levels and a lower cholesterol saturation index. Combination treatment with PUFA and UDCA dissolves cholesterol gallstones in mice by decreasing mucin production, increasing levels of phospholipids and bile acids in bile, and decreasing cholesterol saturation. Further studies of the therapeutic effects of combination PUFA and UDCA treatment in patients with cholesterol gallstones are warranted.


Subject(s)
Cholesterol/metabolism , Fatty Acids, Omega-3/administration & dosage , Gallstones/drug therapy , Ursodeoxycholic Acid/administration & dosage , Animals , Bile Acids and Salts/metabolism , Drug Therapy, Combination , Gallbladder/drug effects , Gallbladder/metabolism , Gallstones/metabolism , Humans , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Phospholipids/metabolism
13.
Clin J Am Soc Nephrol ; 12(4): 653-662, 2017 Apr 03.
Article in English | MEDLINE | ID: mdl-28159828

ABSTRACT

BACKGROUND AND OBJECTIVES: Hyperphosphatemia in kidney transplant recipients has been shown to predict poorer graft and patient survival. However, studies examining hypophosphatemia are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To evaluate the association of serum phosphorus level with patient and graft survival, we performed a retrospective multicenter cohort study. Between January of 1997 and August of 2012, 2786 kidney transplant recipients (41.7±11.4 years; 59.3% men; 73.5% living donors; 26.1% with diabetes; 3.8% with prior history of cardiovascular disease) were classified into seven groups according to serum phosphorus levels 1 year after transplantation, with intervals of 0.5 mg/dl (lowest group, <2.5 mg/dl; highest group, ≥5.0 mg/dl; reference group, 3.5-3.99 mg/dl). Survival analysis was performed by defining baseline time point as 1 year after transplantation. RESULTS: During median follow-up of 78.5 months, 60 patient deaths and 194 cases of graft loss occurred. In multivariate analysis, both lowest and highest serum phosphorus groups were associated with higher mortality, compared with the reference group (hazard ratio [HR], 4.82; 95% confidence interval [95% CI], 1.36 to 17.02; P=0.01; and HR, 4.24; 95% CI, 1.07 to 16.84; P=0.04, respectively). Higher death-censored graft loss was observed in the lowest and highest groups (HR, 3.32; 95% CI, 1.42 to 7.79; P=0.01; and HR, 2.93; 95% CI, 1.32 to 6.49; P=0.01, respectively), despite eGFR exhibiting no difference between the lowest group and reference group (65.4±19.3 versus 61.9±16.7 ml/min per 1.73 m2; P=0.33). Moreover, serum phosphorus showed a U-shape association with patient mortality and graft failure in restricted cubic spline curve analysis. CONCLUSIONS: Serum phosphorus level 1 year after transplantation exhibits a U-shape association with death-censored graft failure and patient mortality in kidney transplant patients characterized by relatively high rate of living donor transplant and low incidence of diabetes and prior cardiovascular disease compared with Western countries.


Subject(s)
Graft Survival , Hyperphosphatemia/mortality , Hypophosphatemia/mortality , Kidney Transplantation/mortality , Phosphorus/blood , Adolescent , Adult , Aged , Calcium/blood , Female , Follow-Up Studies , Humans , Hyperphosphatemia/blood , Hypophosphatemia/blood , Male , Middle Aged , Retrospective Studies , Serum Albumin/metabolism , Survival Rate , Young Adult
14.
Cancer Lett ; 322(2): 213-22, 2012 Sep 28.
Article in English | MEDLINE | ID: mdl-22433711

ABSTRACT

Studies on non-small cell lung cancer (NSCLC) patients with KRAS or BRAF mutations are urgently needed to improve clinical outcomes. We evaluated the cytotoxicities of paclitaxel and sorafenib alone and in combination in NSCLC cell lines with KRAS or BRAF mutations and investigated the mechanism of the interaction between the drugs. We found synergistic antitumor efficacy with paclitaxel followed by sorafenib in in vitro and in vivo models of NSCLC. And, we determined that downregulation of the phosphorylated ERK and Rb, and Mcl-1 plays a critical role in the synergistic activity of the drugs. Further clinical trials are needed to verify the antitumor efficacy of this combination.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Proto-Oncogene Proteins B-raf/genetics , ras Proteins/genetics , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Benzenesulfonates/administration & dosage , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Mutation , Myeloid Cell Leukemia Sequence 1 Protein , Niacinamide/analogs & derivatives , Paclitaxel/administration & dosage , Phenylurea Compounds , Proto-Oncogene Proteins c-bcl-2/genetics , Pyridines/administration & dosage , Retinoblastoma Protein/genetics , Signal Transduction/drug effects , Sorafenib , Tumor Suppressor Protein p53/genetics , Xenograft Model Antitumor Assays
15.
J Agric Food Chem ; 57(19): 9280-3, 2009 Oct 14.
Article in English | MEDLINE | ID: mdl-19728714

ABSTRACT

Structured lipids were synthesized by acidolysis of olive oil and capric acid with an immobilized lipase (Lipozyme TL IM) from Thermomyces lanuginosus. The acidolysis reaction was carried out by incubating a 1:3 molar ratio of olive oil and capric acid under solvent-free reaction systems at 50 degrees C. The effect of water activity on the incorporation of capric acid was investigated, and the tested water activity range was between 0.22 and 0.80. Capric acid incorporation into triacylglycerols of the olive oil increased as the water activity increased, but the degree of acyl migration also increased. Also, the degree of acyl migration of modified olive oils with a similar degree of incorporation was investigated. High degrees of acyl migration occurred at water activities of 0.22 and 0.32 for the degree of incorporation of ca. 50 mol %. Only 8 h of reaction time was required to achieve incorporation of ca. 50 mol % at a water activity of 0.80, and the lowest acyl migration occurred at the same water activity. These results suggest that acyl migration can be efficiently minimized by a shorter reaction time at higher water activity.


Subject(s)
Decanoic Acids/metabolism , Lipase/metabolism , Plant Oils/metabolism , Water/metabolism , Enzymes, Immobilized/metabolism , Olive Oil , Pancreas/enzymology , Plant Oils/chemistry , Triglycerides/metabolism
16.
Am J Med Sci ; 329(1): 1-5, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15654172

ABSTRACT

BACKGROUND: Depression, which is the most common psychological complication in patients with end-stage renal disease (ESRD), has an impact on the clinical outcome and is associated with malnutrition in chronic hemodialysis patients. This study evaluated the effect of antidepression treatment on nutritional status in depressed chronic hemodialysis patients. METHODS: Sixty-two ESRD patients who underwent dialysis for more than 6 months were interviewed and completed a Beck Depression Inventory assessment. Thirty-four patients who had scores greater than 18 on the Beck Depression Inventory score and met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for major depressive disorder were selected to receive paroxetine 10 mg/day and psychotherapy for 8 weeks. The remaining 28 patients were assigned to the control group. Change in the severity of depressive symptoms was ascertained by administering the Hamilton Depression Rating Scale. Nutritional status was evaluated by normalized protein catabolic rate, serum albumin and blood urea nitrogen level. RESULTS: All patients successfully completed 8 weeks of antidepression treatment. Antidepression treatment decreased the severity of depressive symptoms (Hamilton Depression Rating Scale score: 16.6 +/- 7.0 versus 15.1 +/- 6.6, P < 0.01) and increased normalized protein catabolic rate (1.04 +/- 0.24 versus 1.17 +/- 0.29 g/kg/day, P < 0.05), serum albumin (37.3 +/- 2.0 versus 38.7 +/- 3.2 g/l, P < 0.005), and prehemodialysis blood urea nitrogen level (24.3 +/- 5.6 versus 30.2 +/- 7.9 mmol/L, P < 0.001). In the control group, no change was noted during the study period. CONCLUSION: This study suggests that antidepressant medication with supportive psychotherapy can successfully treat depression and improve nutritional status in chronic hemodialysis patients with depression.


Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Depression/drug therapy , Nutritional Status/drug effects , Paroxetine/therapeutic use , Renal Dialysis/psychology , Adult , Depression/etiology , Female , Humans , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/psychology , Kidney Failure, Chronic/therapy , Male , Middle Aged
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