ABSTRACT
Cone photoreceptor diversity allows detection of wavelength information in light, the first step in color (chromatic) vision. In most mammals, cones express opsin photopigments for sensitivity to medium/long (M, "green") or short (S, "blue") wavelengths and are differentially arrayed over the retina. Cones appear early in retinal neurogenesis but little is understood of the subsequent control of diversity of these postmitotic neurons, because cone populations are sparse and, apart from opsins, poorly defined. It is also a challenge to distinguish potentially subtle differences between cell subtypes within a lineage. Therefore, we derived a Cre driver to isolate individual M and S opsin-enriched cones, which are distributed in counter-gradients over the mouse retina. Fine resolution transcriptome analyses identified expression gradients for groups of genes. The postnatal emergence of gradients indicated divergent differentiation of cone precursors during maturation. Using genetic tagging, we demonstrated a role for thyroid hormone receptor ß2 (TRß2) in control of gradient genes, many of which are enriched for TRß2 binding sites and TRß2-regulated open chromatin. Deletion of TRß2 resulted in poorly distinguished cones regardless of retinal location. We suggest that TRß2 controls a bipotential transcriptional state to promote cone diversity and the chromatic potential of the species.
Subject(s)
Receptors, Thyroid Hormone , Retinal Cone Photoreceptor Cells , Animals , Mice , Gene Expression Regulation , Opsins/genetics , Retina , Rod Opsins/geneticsABSTRACT
A meta-analysis was conducted to measure hepatic and pancreatic tumour resection (HPTR) risk factors (RFs) for surgical site wound infections (SSWIs). A comprehensive literature inspection was conducted until February 2023, and 2349 interrelated investigations were reviewed. The nine chosen investigations included 22 774 individuals who were in the chosen investigations' starting point, 20 831 of them were with pancreatic tumours (PTs), and 1934 with hepatic tumours (HTs). Odds ratio (OR) and 95% confidence intervals (CIs) were used to compute the value of the HPTR RFs for SSWIs using dichotomous and continuous approaches, and a fixed or random model. HT patients with biliary reconstruction had significantly higher SSWI (OR, 5.81; 95% CI, 3.42-9.88, P < .001) than those without biliary reconstruction. Nevertheless, there was no significant difference between individuals with PT who underwent pancreaticoduodenectomy and those who underwent distal pancreatectomy in SSWI (OR, 1.63; 95% CI, 0.95-2.77, P = .07). HT individuals with biliary reconstruction had significantly higher SSWI compared with those without biliary reconstruction. Nevertheless, there was no significant difference between PT individuals who underwent pancreaticoduodenectomy and those who underwent distal pancreatectomy in SSWI. However, owing to the small number of selected investigations for this meta-analysis, care must be exercised when dealing with its values.
Subject(s)
Liver Neoplasms , Pancreatic Neoplasms , Humans , Pancreas/surgery , Pancreatectomy/adverse effects , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/etiology , Pancreatic Neoplasms/pathology , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Surgical Wound Infection/surgery , Liver Neoplasms/surgeryABSTRACT
PURPOSE: Cancer treatment may relate to appetite reduction and malnutrition. We investigated taste alterations and dish-type preferences during chemo- and/or radiation therapy in breast cancer patients. METHODS: Breast cancer patients (BC, n = 59) scheduled to receive cancer therapy and healthy subjects (control group or CTRL, n = 49) were voluntarily recruited. Taste detection thresholds (DTs) and recognition thresholds (RT) were compared between pre-treatment BC patients and CTRL for sweet (sucrose), salty (NaCl), bitter (caffeine), and sour (citric acid) solutions. Changes in taste thresholds and dish preferences during treatment were monitored in the BC group. Blood chemistry and anthropometric data were collected. RESULTS: At baseline, BC patients demonstrated lower sweet and salty DTs and RTs and a higher sour RT compared to CTRL. Bitter DT and RT were similar in both groups. Mild/soft dishes were preferred over fried/oily dishes by BC patients. Throughout treatment in BC patients, sweet thresholds significantly declined, while salty, bitter, and sour DTs and RTs were not affected, and there was no increase in preference for a dish. However, preference towards mild/soft dishes remained. While sweet-sour fruits and sweetened nuts were not favored during therapy. CONCLUSIONS: Sensitivities to sweet, salty, and sour but not bitter tastes differed between BC patients and CTRL. During treatment, sweet taste sensitivity increased while other tastes were unaffected. BC patients preferred mild/soft dishes over fried and sweetened dishes compared to CTRL. Our findings may contribute to developing dishes for breast cancer patients to increase food intake and thereby lower the risk of malnutrition.
Subject(s)
Breast Neoplasms/psychology , Food Preferences/psychology , Taste/physiology , Female , Humans , Male , Middle Aged , Pilot ProjectsABSTRACT
A new class of luminescent, heterotrimetallic supramolecular constructs partnering two bis-cyclometalated iridium centers with a diimine platinum acetylide center is introduced. Whereas most supramolecular constructs featuring cyclometalated iridium involve elaborate bridging ligands and are prepared under forcing conditions with low to moderate yields, the three Ir-Pt-Ir complexes described here are prepared at room temperature from simple precursors and isolated in near-quantitative yields. ESI-MS, NMR spectroscopy, and diffusion ordered spectroscopy confirm the identity and homogeneity of the trimetallic products. In comparison with monometallic model complexes, analysis of UV/Vis absorption, steady-state photoluminescence and time-resolved emission reveals the impacts of supramolecular assembly on the photophysical properties. UV/Vis absorption and cyclic voltammetry suggest perturbation of some frontier orbital energies as a result of assembly, and the emission spectra and lifetimes reveal efficient excited-state energy transfer via a Dexter mechanism, and show that the site of luminescence (platinum or iridium) depends on the identity of the cyclometalating ligand bound to iridium.
ABSTRACT
PURPOSE: This study evaluates the effect of an enhanced recovery after surgery (ERAS)-based nutrition support protocol on oral intake and weight change in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: A 14-day postoperative nutrition support protocol was developed to initiate oral intake after 1 week of enteral tube feeding and parenteral nutrition (early oral feeding, EOF). Forty-eight patients who underwent PPPD participated in the study (non-EOF, n = 23; EOF, n = 25). General information, nutrition supply route and amount, blood chemistry, and weight changes were tracked. RESULTS: The enteral tube feeding duration was 2.7 days shorter in the EOF group than in the non-EOF group. Furthermore, the EOF group started oral liquid and soft diets 1.1 and 2.5 days earlier than the non-EOF group, respectively. Compared with the non-EOF group, the EOF group reported a higher energy intake (22.1%; p = 0.001) and protein intake (17.4%; p = 0.000) via oral route. Although cumulative energy and protein intakes were similar in both groups, weight reduction in the EOF group (3.6 ± 0.1%, 2.2 ± 0.7 kg) was significantly less than the non-EOF group (8.2 ± 0.9%, 5.2 ± 0.5 kg). The blood levels of total protein and transferrin increased and prealbumin decreased, regardless of the EOF application. Serum albumin increased significantly only in the EOF group. CONCLUSION: The EOF protocol developed for post-PPPD patients enables the early initiation and increase in the amount of oral intake while significantly alleviating weight loss.
Subject(s)
Organ Sparing Treatments/methods , Pancreaticoduodenectomy/methods , Pylorus/surgery , Biomarkers/blood , Dietary Proteins/administration & dosage , Energy Intake , Enteral Nutrition/methods , Female , Humans , Male , Middle Aged , Parenteral Nutrition/methods , Postoperative Care/methods , Recovery of Function , Weight Loss/physiologyABSTRACT
Ultraviolet B (UVB) irradiation causes adverse effects on the skin. Corn silk contains flavonoids and other bioactive compounds and antioxidants, which may prevent skin photoaging through antioxidant and anti-inflammatory effects. We aimed to investigate the potential photoprotective effects of dietary corn silk on UVB-induced skin damage in mice and the mechanisms behind these effects on human skin cells. Oral administration of corn silk water extract (CS) (2 or 4 g/kg/day) for 19 weeks decreased epidermal thickness, wrinkle formation, and positive staining for PCNA, Ki67, and 8-OHdG, and increased collagen staining in UVB-irradiated SKH-1 hairless mice compared with controls. The pro-inflammatory NF-κB target genes (IL-1ß, iNOS, and COX-2) and MMP-9 expressions were lower in the CS groups, and TGF-ß/Smad signaling increased. Low skin lipid peroxidation and blood DNA oxidation levels and high blood glutathione were detected. Antioxidant transcription factor Nrf2-related catalase and SOD1 proteins and glutaredoxin mRNA levels increased. The results of CS extract treatment and UVB irradiation in HaCaT cells showed the same results in Nrf2 and NF-κB target genes. An LC-MS/MS analysis showed that the CS extract contained potential antioxidants, which might have contributed to its anti-photoaging effects in tissues and cells. CS extract may reduce UVB-induced skin damage through antioxidant and anti-inflammatory mechanisms.
Subject(s)
Antioxidants/administration & dosage , Silk/administration & dosage , Skin Aging/drug effects , Ultraviolet Rays/adverse effects , Zea mays/chemistry , Administration, Oral , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Cell Line , Chromatography, Liquid , Disease Models, Animal , Flavonoids/chemistry , Humans , Lipid Peroxidation/drug effects , Mice , Mice, Hairless , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Silk/chemistry , Silk/pharmacology , Tandem Mass SpectrometryABSTRACT
Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation. However, the molecular mechanisms by which hyperglycemia affects osteogenic differentiation are yet to be clarified. This study aimed to investigate whether the aberrant increase in protein O-linked-ß-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia. To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2). Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression. The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation. Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase. These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing ß-N-acetylglucosaminidase. Our findings suggest that excessive protein O-GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.
Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Cell Differentiation/drug effects , Osteogenesis/drug effects , Transforming Growth Factor beta/pharmacology , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Cells, Cultured , Collagen Type I/genetics , Collagen Type I/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Enzyme Inhibitors/pharmacology , Glucosamine/pharmacology , Glucose/pharmacology , Glycosylation/drug effects , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Mice , Myoblasts/cytology , Myoblasts/drug effects , Myoblasts/metabolism , N-Acetylglucosaminyltransferases/antagonists & inhibitors , N-Acetylglucosaminyltransferases/genetics , N-Acetylglucosaminyltransferases/metabolism , Periodontal Ligament/cytology , Periodontal Ligament/drug effects , Periodontal Ligament/metabolism , Recombinant Proteins/pharmacology , Sp7 Transcription Factor/genetics , Sp7 Transcription Factor/metabolism , Transcription, Genetic/drug effectsABSTRACT
BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.
Subject(s)
Brain/drug effects , Dyskinesia, Drug-Induced/prevention & control , Levodopa/therapeutic use , Magnoliopsida , Parkinson Disease/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Brain/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Disease Models, Animal , Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism , Dyskinesia, Drug-Induced/etiology , Enkephalins/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Levodopa/administration & dosage , Levodopa/adverse effects , Levodopa/pharmacology , Male , Mice, Inbred C57BL , Movement , Parkinson Disease/metabolism , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Substance P/metabolismABSTRACT
Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1.
Subject(s)
Apoptosis/physiology , MAP Kinase Kinase Kinase 5/metabolism , MAP Kinase Kinase Kinases/metabolism , Signal Transduction/physiology , Apoptosis/drug effects , Apoptosis/genetics , Caspase 3/genetics , Caspase 3/metabolism , Dual-Specificity Phosphatases , Humans , MAP Kinase Kinase Kinase 5/genetics , MAP Kinase Kinase Kinases/genetics , Neuroblastoma/genetics , Phosphotransferases/genetics , Phosphotransferases/metabolism , Protein Processing, Post-Translational/drug effects , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction/drug effects , Signal Transduction/geneticsABSTRACT
The purposes of this study were (1) to identify MBTI (Myers-Briggs Type Indicator) personality profiles of Korean cabin crew in Middle Eastern airlines, (2) to determine whether MBTI personality affects their cross-cultural adjustment competency, occupational competency, and coping competency, and (3) to analyze the impact of these variables on their mental health and turnover intention. Furthermore, we verified (4) the moderating effect of cabin crew's previous overseas experience on the relationship between cross-cultural adjustment competency and turnover intention. MBTI-Form M test and a survey questionnaire were distributed to 185 Korean cabin crew members in Middle Eastern airlines, and 172 valid datapoints were used for analysis. It was revealed that the cabin crew members showed significantly different levels of cross-cultural adjustment competency, occupational competency, and coping competency depending on their personality traits. Furthermore, those with higher cross-cultural adjustment competency and stress coping are more likely to have positive mental health, which also had an influence on lowering their turnover intention. Occupational competency had no significant association with mental health; however, it directly affects turnover intention. The findings will contribute not only to career plan guidelines for cabin crew aspirants, but also to airlines' recruitment strategies as well as human resources management in aviation industry.
Subject(s)
Intention , Mental Health , Adaptation, Psychological , Cross-Cultural Comparison , Humans , Mental Competency , Personality , Personality Inventory , Republic of KoreaABSTRACT
Aging has been implicated in the alteration of taste acuity. Diet can affect taste sensitivity. We aimed to investigate the types of tastes altered in elderly Korean people and factors associated with taste alteration in relation to dietary intake and other factors. Elderly participants (≥65 years) and young adults were assessed to determine their recognition thresholds (RT) for sweet, salty, bitter, sour, and umami tastes. Elderly participants were further surveyed for dietary intake and non-nutritional factors. Five taste RTs were correlated with age, but only four taste RTs, except sweetness, differed between the elderly participants and young adults. Inadequate intake of iron, thiamin, folic acid, zinc, and phosphorus among the elderly participants was related to elevated taste RT levels, except for bitter taste. In both correlation and regression analyses, only salty and sour RTs were associated with energy, iron, thiamin, fiber, vitamin C, and riboflavin levels in the elderly participants. The elderly participants' taste RTs exhibited strong associations with quality of life (QOL) but showed partial relationships with physical activity, number of medicine intakes, social gatherings, and education. Taste sensitivity may decrease with age, which is further influenced by insufficient dietary intake, especially iron and thiamin, and QOL.
Subject(s)
Aging/psychology , Diet/psychology , Eating/psychology , Quality of Life/psychology , Taste , Adult , Aged , Female , Food Preferences/psychology , Humans , Male , Regression Analysis , Republic of Korea , Taste Threshold , Young AdultABSTRACT
Parabens are generally used as preservatives in foods, pharmaceuticals, and various other commercial products. Among them, ethylparaben has weaker estrogenic characteristics than endogenous estrogen. However, growing evidence indicates that ethylparaben has an adverse effect on various human tissues. Here, we investigated whether ethylparaben induces cell death by affecting cell viability, cell proliferation, cell cycle, and apoptosis using the human placenta cell line BeWo. Ethylparaben significantly decreased cell viability in a dose-dependent manner. It caused cell cycle arrest at sub-G1 by reducing the expression of cyclin D1, whereas it decreased the cell proportion at the G0/G1 and S phases. Furthermore, we verified that ethylparaben induces apoptotic cell death by enhancing the activity of Caspase-3. Taken together, our results suggest that ethylparaben exerts cytotoxic effects in human placental BeWo cells via cell cycle arrest and apoptotic pathways.
ABSTRACT
Protein phosphorylation plays critical roles in many regulatory mechanisms controlling cell activities and thus involved in various diseases. The cellular equilibrium of phosphorylation is regulated through the actions of protein kinases and phosphatases. Therefore, these regulatory proteins have emerged as promising targets for drug development. In this study, we screened protein tyrosine phosphatases (PTPs) by in vitro phosphatase assays to identify PTPs that are inhibited by 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), a potent inhibitor of SHP-1 and SHP-2 PTPs. Phosphatase activity of dual-specificity protein phosphatase 26 (DUSP26) was decreased by the inhibitor in a dose-dependent manner. Kinetic studies with NSC-87877 and DUSP26 revealed a competitive inhibition. NSC-87877 effectively inhibited DUSP26-mediated dephosphorylation of p38, a member of mitogen-activated protein kinase (MAPK) family. Since DUSP26 is involved in survival of anaplastic thyroid cancer (ATC) cells, NSC-87877 could be a therapeutic reagent for treating ATC.
Subject(s)
Dual-Specificity Phosphatases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Mitogen-Activated Protein Kinase Phosphatases/antagonists & inhibitors , Quinolines/pharmacology , Cell Line , Enzyme Inhibitors/chemistry , Humans , Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 6/antagonists & inhibitors , Quinolines/chemistryABSTRACT
Protein phosphorylation plays critical roles in the regulation of protein activity and cell signaling. The level of protein phosphorylation is controlled by protein kinases and protein tyrosine phosphatases (PTPs). Disturbance of the equilibrium between protein kinase and PTP activities results in abnormal protein phosphorylation, which has been linked to the etiology of several diseases, including cancer. In this study, we screened protein tyrosine phosphatases (PTPs) by in vitro phosphatase assays to identify PTPs that are inhibited by bis (4-trifluoromethyl-sulfonamidophenyl, TFMS)-1,4-diisopropylbenzene (PTP inhibitor IV). PTP inhibitor IV inhibited DUSP14 phosphatase activity. Kinetic studies with PTP inhibitor IV and DUSP14 revealed a competitive inhibition, suggesting that PTP inhibitor IV binds to the catalytic site of DUSP14. PTP inhibitor IV effectively and specifically inhibited DUSP14-mediated dephosphorylation of JNK, a member of the mitogen-activated protein kinase (MAPK) family.
Subject(s)
Dual-Specificity Phosphatases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , MAP Kinase Kinase 4/metabolism , Mitogen-Activated Protein Kinase Phosphatases/antagonists & inhibitors , Protein Tyrosine Phosphatases/antagonists & inhibitors , Sulfonamides/pharmacology , Cell Line , Humans , PhosphorylationABSTRACT
Small interfering synthetic double-stranded RNA (siRNA) was applied to suppress the expression of the human cytotoxic- T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) gene transformed in transgenic rice cell cultures. The sequence of the 21-nucleotide siRNA was deliberately designed and synthesized with overhangs to inactivate the expression of hCTLA4Ig. The chemically synthesized siRNA duplex was combined with polyethyleneimine (PEI) at a mass ratio of 1:10 (0.33 microg siRNA:3.3 microg PEI) to produce complexes. The siRNA complexes (siRNA+PEI) were labeled with Cy3 in order to subsequently confirm the delivery by fluorescent microscopy. In addition, the cells were treated with sonoporation at 40 kHz and 419 W for 90 s to improve the delivery. The siRNA complexes alone inhibited the expression of hCTLA4Ig to 45% compared with control. The siRNA complexes delivered with sonoporation downregulated the production of hCTLA4Ig to 73%. Therefore, we concluded that the delivery of siRNA complexes into plant cells could be enhanced successfully by sonoporation.
Subject(s)
Gene Transfer Techniques , Oryza/metabolism , RNA Interference , RNA, Small Interfering/metabolism , Antigens, CD/genetics , Antigens, CD/metabolism , CTLA-4 Antigen , Cell Culture Techniques , Cell Survival , Humans , Oryza/cytology , Oryza/genetics , Plants, Genetically Modified/cytology , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , RNA, Small Interfering/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolismABSTRACT
We examined the effect of high fat oral nutritional supplement (HFS) on the nutritional status, oral intake, and serum metabolites of postoperative pancreaticobiliary cancer patients. Pancreaticobiliary cancer patients were voluntarily recruited. The HFS group received postoperative oral high fat supplementation (80% of total calories from fat; n = 12) until discharge; the control group (non-HFS; n = 9) received none. Dietary intake, anthropometry, blood chemistry, nutritional risk index (NRI), and serum metabolites analyzed by liquid chromatography tandem mass spectrometry were evaluated. Overall, cumulative caloric supply via parental and oral/enteral routes were not different between groups. However, oral fat intake, caloric intake, and NRI scores of the HFS group were higher than those of the non-HFS group with increased oral meal consumption. Oral caloric, fat, and meal intakes correlated with NRI scores. Metabolomics analysis identified 195 serum metabolites pre-discharge. Oral fat intake was correlated with 42 metabolites relevant to the glycerophospholipid pathway. Oral high fat-specific upregulation of sphingomyelin (d18:1/24:1), a previously reported pancreatic cancer-downregulated metabolite, and lysophosphatidylcholine (16:0) were associated with NRI scores. Provision of HFS in postoperative pancreatic cancer patients may facilitate the recovery of postoperative health status by increasing oral meal intake, improving nutritional status, and modulating serum metabolites.
Subject(s)
Dietary Fats/therapeutic use , Dietary Supplements , Malnutrition/prevention & control , Metabolome , Nutritional Status , Pancreatectomy , Pancreatic Neoplasms/surgery , Administration, Oral , Aged , Dietary Fats/administration & dosage , Dietary Fats/blood , Dietary Fats/pharmacology , Energy Intake , Feeding Behavior , Female , Humans , Lysophosphatidylcholines/blood , Male , Malnutrition/blood , Malnutrition/etiology , Metabolome/drug effects , Middle Aged , Nutritional Requirements , Pancreatectomy/adverse effects , Pancreatic Neoplasms/blood , Postoperative Complications/blood , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Sphingomyelins/bloodABSTRACT
Chemotherapy may negatively affect nutritional status and quality of life (QOL) in pancreatic cancer patients. Our aim was to investigate the beneficial effects of oral nutrition supplements (ONS) on pancreatic and bile duct cancer patients undergoing chemotherapy. Among patients with progressive pancreatic and bile duct cancer receiving chemotherapy, the ONS group (n = 15) received two packs of ONS daily for 8 weeks while the non-ONS group (n = 19) did not. Anthropometric measures, dietary intake, nutritional status, and quality of life were assessed. ONS significantly increased daily intakes of energy, carbohydrates, proteins, and lipids at 8 weeks compared to the baseline. After 8 weeks, fat mass significantly increased in the ONS group. For patients in their first cycle of chemotherapy, body weight, fat-free mass, skeletal muscle mass, body cell mass, and fat mass increased in the ONS group but decreased in the non-ONS group. Fat mass increased in second or higher cycle only in the ONS group. Patient-generated subjective global assessments (PG-SGA) and fatigue scores in the Quality of Life Questionnaire Core 30 (QLQ-C30) improved in the ONS group. ONS might improve nutritional status by increasing fat mass and/or maintaining the body composition of pancreatic and bile duct cancer patients with chemotherapy, especially those in the first cycle, and alleviate fatigue symptoms.
Subject(s)
Bile Duct Neoplasms/therapy , Dietary Supplements , Nutrition Therapy/methods , Pancreatic Neoplasms/therapy , Aged , Bile Duct Neoplasms/drug therapy , Body Composition , Body Weight , Diet , Energy Intake , Female , Humans , Male , Nutritional Status , Pancreatic Neoplasms/drug therapy , Prospective Studies , Quality of Life , Surveys and QuestionnairesABSTRACT
A ketogenic diet is a potential adjuvant cancer therapy that limits glucose availability to tumours while fuelling normal tissues with ketone bodies. We examined the effect of a low carbohydrate ketogenic diet (LCKD) (80% kcal from fat, ketogenic ratio 1.75:1, w/w) compared to a general hospital diet (GD) on serum metabolic profiles in patients (n = 18, ≥ 19 years old) who underwent pancreatectomy for pancreatobiliary cancer. Serum samples collected preoperatively (week 0) and after the dietary intervention (week 2) were analysed with a nontargeted metabolomics approach using liquid chromatography-tandem mass spectrometry. Serum ß-hydroxybutyrate and total ketone levels significantly increased after 2 weeks of LCKD compared to GD (p < 0.05). Principal component analysis score plots and orthogonal partial least squares discriminant analysis also showed significant differences between groups at week 2, with strong validation. In all, 240 metabolites differed between LCKD and GD. Pathways including glycerophospholipid and sphingolipid metabolisms were significantly enriched in the LCKD samples. LCKD decreased C22:1-ceramide levels, which are reported to be high in pancreatic cancer, while increasing lysophosphatidylcholine (18:2), uric acid, citrulline, and inosine levels, which are generally low in pancreatic cancer. Postoperative LCKD might beneficially modulate pancreatic cancer-related metabolites in patients with pancreatobiliary cancer.
Subject(s)
Bile Duct Neoplasms/therapy , Diet, Carbohydrate-Restricted/methods , Diet, Ketogenic/methods , Duodenal Neoplasms/therapy , Metabolomics/methods , Pancreatectomy/methods , Pancreatic Neoplasms/therapy , 3-Hydroxybutyric Acid/blood , Aged , Bile Duct Neoplasms/metabolism , Chromatography, Liquid , Duodenal Neoplasms/metabolism , Female , Humans , Ketones/blood , Male , Middle Aged , Pancreatic Neoplasms/metabolism , Pilot Projects , Tandem Mass SpectrometryABSTRACT
Parkinson's disease is the second most common neurodegenerative disease. Patients with Parkinson's disease can be treated with a combination of acupuncture and herbal medicine, but studies on the synergistic effects of the combined treatment have not yet been conducted. Thus, we subjected an MPTP-induced Parkinson's disease mouse model to the combined treatment. We used acupoint GB34 for acupuncture and modified Chunggantang (KD5040) as the herbal medicine, as they have been reported to be effective in Parkinson's disease. We investigated the suboptimal dose of KD5040 and then used this dose in the combined treatment. The results showed that the combined treatment had a synergistic effect on improvements in abnormal motor function and neurodegeneration compared with the use of acupuncture or herbal medicine alone. The combined treatment also had a neuroprotective effect via the PI3K/AKT and MAPK/ERK signaling pathways. These findings suggest that the combined treatment with acupuncture and KD5040 can help improve the symptoms of Parkinson's disease.
ABSTRACT
PURPOSE: Nasopharyngeal inflammatory pseudotumor (NIPT) is hard to differentiate from infiltrating nasopharyngeal carcinoma (NPC) on conventional magnetic resonance imaging (MRI). The purpose of this study is to determine whether discrepant lesion sizes estimated on T1- and fat-suppressed T2-weighted images can help distinguish between NIPT and NPC. METHODS: We retrospectively reviewed MRI data of histologically proven 14 NIPTs and 18 infiltrating NPCs. We measured the area of the lesion on contrast-enhanced T1-weighted, unenhanced T1-weighted, and fat-suppressed T2-weighted images by placing the largest possible polygonal region-of-interest within the lesion at the same level. Using lesion size measured on contrast-enhanced T1-weighted image as the reference, we calculated and compared area ratio of T1 (ART1) and area ratio of T2 (ART2) between NIPTs and NPCs. For validation, we also undertook a double-blinded study by two reviewers and assessed the diagnostic performance and interobserver agreement. RESULTS: For NIPTs, ART2 (median, 0.48; range, 0.18-0.97) was statistically significantly less than ART1 (median, 1.01; range, 0.80-1.99), while these values were not significantly different for NPCs. The interobserver agreement in differentiating between NIPT and NPC was good, with a sensitivity of 93% and a specificity of 83%-94%. CONCLUSION: In contrast to NPCs, NIPTs appear smaller on fat-suppressed T2-weighted images than on T1-weighted images. This discrepancy in the lesion size estimated on T1-weighted and fat-suppressed T2-weighted images may provide a simple and consistent way to differentiate between NIPTs and NPCs on conventional MRI.