RESUMO
Prolyl hydroxylase domain proteins (PHDs) control cellular adaptation to hypoxia. PHDs are found involved in inflammatory bowel disease (IBD); however, the exact role of PHD3, a member of the PHD family, in IBD remains unknown. We show here that PHD3 plays a critical role in maintaining intestinal epithelial barrier function. We found that genetic ablation of Phd3 in intestinal epithelial cells led to spontaneous colitis in mice. Deletion of PHD3 decreases the level of tight junction protein occludin, leading to a failure of intestinal epithelial barrier function. Further studies indicate that PHD3 stabilizes occludin by preventing the interaction between the E3 ligase Itch and occludin, in a hydroxylase-independent manner. Examination of biopsy of human ulcerative colitis patients indicates that PHD3 is decreased with disease severity, indicating that PHD3 down-regulation is associated with progression of this disease. We show that PHD3 protects intestinal epithelial barrier function and reveal a hydroxylase-independent function of PHD3 in stabilizing occludin. These findings may help open avenues for developing a therapeutic strategy for IBD.
Assuntos
Mucosa Intestinal/fisiologia , Ocludina/fisiologia , Pró-Colágeno-Prolina Dioxigenase/fisiologia , Animais , Colite/genética , Colite/prevenção & controle , Deleção de Genes , Células HEK293 , Humanos , Camundongos , Camundongos TransgênicosRESUMO
Intestinal epithelial cells (IECs) have critical roles in maintaining homeostasis of intestinal epithelium. Endoplasmic reticulum (ER) stress is implicated in intestinal epithelium homeostasis and inflammatory bowel disease; however, it remains elusive whether IRE1α, a major sensor of ER stress, is directly involved in these processes. We demonstrate here that genetic ablation of Ire1α in IECs leads to spontaneous colitis in mice. Deletion of IRE1α in IECs results in loss of goblet cells and failure of intestinal epithelial barrier function. IRE1α deficiency induces cell apoptosis through induction of CHOP, the pro-apoptotic protein, and sensitizes cells to lipopolysaccharide, an endotoxin from bacteria. IRE1α deficiency confers upon mice higher susceptibility to chemical-induced colitis. These results suggest that IRE1α functions to maintain the intestinal epithelial homeostasis and plays an important role in defending against inflammation bowel diseases.
Assuntos
Colite/prevenção & controle , Retículo Endoplasmático/metabolismo , Endorribonucleases/fisiologia , Mucosa Intestinal/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Sequência de Bases , Linhagem Celular , Primers do DNA , Endorribonucleases/genética , Homeostase , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/genéticaRESUMO
BACKGROUND: Peritoneal air exposure is a common phenomenon in abdominal surgery, but long-term exposure could induce intestinal inflammatory responses, resulting in delayed recovery of gastrointestinal motility after surgery. High-fat enteral nutrition has been reported to ameliorate inflammation in many diseases. In the present study, we investigated whether high-fat enteral nutrition could control intestinal inflammation and improve intestinal motility after peritoneal air exposure. METHODS: Male adult rats were administrated saline, low-fat enteral nutrition, or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Control rats underwent anesthesia without laparotomy and received saline. Intestinal motility was assessed 24 h after surgery by charcoal transport assay; systemic inflammation was assessed by analyzing serum levels of tumor necrosis factor α, interleukin (IL)-1ß, IL-6, and IL-10; and intestinal inflammation was assessed by analyzing myeloperoxidase activity and concentrations and gene expression of tumor necrosis factor α, IL-1ß, IL-6, and IL-10 in the intestinal tissue. RESULTS: Peritoneal air exposure decreased intestinal motility significantly compared with the control group (P < 0.05). The systemic and intestinal inflammatory parameters were also much higher in the peritoneal air exposure groups than in the control group. Both low-fat and high-fat enteral nutrition increased intestinal motility and reduced systemic and intestinal inflammatory parameter levels to different degrees. However, high-fat enteral nutrition significantly improved the negative alterations in these biochemical parameters compared with low-fat enteral nutrition (P < 0.05). CONCLUSIONS: These results suggest that high-fat enteral nutrition might be able to control intestinal inflammation and improve intestinal motility after peritoneal air exposure. Thus, the perioperative administration of high-fat enteral nutrition may be a promising treatment to enhance the recovery of intestinal motility after surgery.
Assuntos
Gorduras na Dieta/uso terapêutico , Nutrição Enteral , Enterite/prevenção & controle , Motilidade Gastrointestinal , Complicações Pós-Operatórias/prevenção & controle , Animais , Citocinas/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Peroxidase/metabolismo , Distribuição Aleatória , Ratos Sprague-DawleyRESUMO
BACKGROUND: Peritoneal air exposure is needed in open abdominal surgery, but long-time exposure could induce intestinal mucosal barrier dysfunction followed by many postoperative complications. High-fat enteral nutrition can ameliorate intestinal injury and improve intestinal function in many gastrointestinal diseases. In the present study, we investigated the effect of high-fat enteral nutrition on intestinal mucosal barrier after peritoneal air exposure and the underlying mechanism. METHODS: Male adult rats were administrated saline, low-fat or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Rats undergoing anesthesia without laparotomy received saline as control. Twenty four hours after surgery, samples were collected to assess intestinal mucosal barrier changes in serum D-lactate levels, intestinal permeability, intestinal tight junction protein ZO-1 and occludin levels, and intestinal histopathology. The levels of malondialdehyde and the activity of superoxide dismutase in the ileum tissue were also measured to assess the status of intestinal oxidative stress. RESULTS: High-fat enteral nutrition significantly decreased the serum D-lactate level and increased the intestinal tight junction protein ZO-1 level when compared to the group treated with low-fat enteral nutrition (P < 0.05). Meanwhile, histopathologic findings showed that the intestinal mucosal injury assessed by the Chiu's score and the intestinal epithelial tight junction were also improved much more in the high-fat enteral nutrition-treated group (P < 0.05). In addition, the intestinal malondialdehyde level was lower, and the intestinal superoxide dismutase activity was higher in the high-fat enteral nutrition-treated group than that in the low-fat enteral nutrition-treated group (P < 0.05). CONCLUSIONS: These results suggest that high-fat enteral nutrition could reduce intestinal mucosal barrier damage after peritoneal air exposure, and the underlying mechanism may be associated with its antioxidative action. Perioperative administration of high-fat enteral nutrition may be a promising intervention to preserve intestinal mucosal barrier function in open abdominal surgery.
Assuntos
Ar , Dieta Hiperlipídica , Nutrição Enteral/métodos , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Laparotomia/efeitos adversos , Peritônio , Animais , Biomarcadores/metabolismo , Íleo/patologia , Mucosa Intestinal/patologia , Masculino , Assistência Perioperatória/métodos , Permeabilidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Distribuição Aleatória , Ratos , Junções Íntimas/metabolismoRESUMO
Hypoxia has been proved to be a typical character of solid tumors. Tumor cells prefer to use glucose through the glycolysis pathway instead of aerobic respiration. However, the precise molecular mechanism underlying this so-called Warburg effect remains elusive. In the current study, siRNA was synthesized and transfected into BxPC-3 cell line to silence the expression of HIF-1α gene. It was found that hypoxia induced hypoxia-inducible factor 1α (HIF-1α) overexpression in BxPC-3 cells, enhanced the expression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A, thus facilitating glycolysis and making tumor cells more tolerant to hypoxic stress. The silencing of HIF-1α gene significantly attenuated glycolysis under hypoxic conditions, inhibited the growth and invasion ability of BxPC-3 cells, and enhanced hypoxia-induced cell apoptosis.
Assuntos
Inativação Gênica , Glicólise/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Animais , Apoptose , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Isoenzimas/genética , L-Lactato Desidrogenase/genética , Lactato Desidrogenase 5 , Ácido Láctico/biossíntese , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Interferente Pequeno/genética , TransfecçãoRESUMO
Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factor is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-polymerase chain reaction, Western blot, and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling, respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs and is a potential target for the prevention of age-related osteoporosis.
Assuntos
Adipogenia , Envelhecimento , Proteína Forkhead Box O3 , Células-Tronco Mesenquimais , Osteogênese , Animais , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Envelhecimento/genética , Envelhecimento/metabolismo , Osteogênese/genética , Camundongos , Adipogenia/genética , Diferenciação Celular/genética , Camundongos Endogâmicos C57BL , Osteoporose/metabolismo , Osteoporose/patologia , Osteoporose/genética , Osso e Ossos/metabolismo , Transdução de Sinais , PPAR gama/metabolismo , PPAR gama/genética , Masculino , Células Cultivadas , Receptores Notch/metabolismo , Receptores Notch/genéticaRESUMO
Paired box (PAX) 2, a transcription factor, plays a critical role in embryogenesis. When aberrantly expressed in adult tissues, it generally exhibits oncogenic properties. However, the underlying mechanisms remain unclear. We reported previously that the expression of PAX2 was up-regulated in human colon cancers. However, the role of PAX2 in colon cancer cells has yet to be determined. The aim of this study is to determine the function of PAX2 in colon cancer cells and to investigate the possible mechanisms underlain. We find that knockdown of PAX2 inhibits proliferation and xenograft growth of colon cancer cells. Inhibition of PAX2 results in a decreased expression of cyclin D1. Expression of cyclin D1 is found increased in human primary colon malignant tumors, and its expression is associated with that of PAX2. These data indicate that PAX2 is a positive regulator of expression of cyclin D1. We find that knockdown of PAX2 inhibits the activity of AP-1, a transcription factor that induces cyclin D1 expression, implying that PAX2 induces cyclin D1 through AP-1. PAX2 has little effect on expression of AP-1 members including c-Jun, c-Fos, and JunB. Our data show that PAX2 prevents JunB from binding c-Jun and enhances phosphorylation of c-Jun, which may elevate the activity of AP-1. Taken together, these results suggest that PAX2 promotes proliferation of colon cancer cells through AP-1.
Assuntos
Proliferação de Células , Neoplasias do Colo/metabolismo , Ciclina D1/genética , Fator de Transcrição PAX2/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Regulação para Cima , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , Ciclina D1/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Transcrição PAX2/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismoRESUMO
Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors. However, the expression pattern of PKM2 in colorectal cancer (CRC) and the correlation between PKM2 expression and CRC remains unclear. The aim of this study is to investigate PKM2 expression and its possible role in CRC. We found that expression of PKM2 was increased in CRC and the increased PKM2 expression was associated with later stage and lymph metastasis of the tumors. Knockdown of PKM2 suppressed the aerobic glycolysis and decreased lactate production of colon cancer RKO cells. Knockdown of PKM2 repressed proliferation and migration of the cells. Inhibition of PKM2 suppressed xenograft tumor growth of RKO cells in vivo. These results suggest that the expression of PKM2 plays a critical role in development of CRC, and it may provide a growth advantage for colon cancer cells. Thus, PKM2 might be a potential therapeutic target for CRC.
Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/enzimologia , Piruvato Quinase/genética , Regulação para Cima , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica , Glicólise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Piruvato Quinase/metabolismo , Carga TumoralRESUMO
Prolyl hydroxylase domain proteins (PHDs) hydroxylate HIFα in the presence of oxygen, leading to HIFα proteasomal destruction. The PHDs family comprises PHD1, 2, and 3. Recent studies indicate that, in addition to HIFα, PHDs have other substrates. Paired box (Pax) 2, a transcription factor, was found aberrantly expressed in a variety of cancers. However, the underlying mechanisms remain unknown. Here we demonstrate that PHD3 is a negative regulator of expression of Pax2. We found that PHD3 bound to Pax2 and mediated Pax2 destruction directly. Inhibition of PHD3 hydroxylase activity led to upregulation of Pax2 protein but not mRNA level. We found that Pax2 protein was increased and PHD3 protein was decreased in colorectal cancer, and the increased Pax2 was associated with decreased PHD3. Our results suggest that PHD3 targets Pax2 for destruction. The findings may disclose a mechanism for the regulation of Pax2 expression in cancer cells.
Assuntos
Neoplasias Colorretais/metabolismo , Dioxigenases/metabolismo , Fator de Transcrição PAX2/metabolismo , Linhagem Celular Tumoral , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia , Fator de Transcrição PAX2/antagonistas & inibidores , Fator de Transcrição PAX2/genética , Transcrição GênicaRESUMO
Increased production of hormone-sensitive lipase (HSL) protein has been demonstrated to be the major cause behind enhanced lipolysis in cancer cachexia. The mechanism governing this alteration is unknown and was presently investigated. This study was conducted to detect the expression of relevant receptors in the adipocytes of cancer cachexia patients, and to elucidate their implication in the increased lipolysis. Gene expressions of beta1-adrenoceptor (ADRB1), beta2-adrenoceptor (ADRB2), beta3-adrenoceptor (ADRB3), alpha2C-adrenoceptor (ADRA2C), natriuretic peptide receptor A (NPRA), insulin receptor (INSR), and HSL were determined in adipose tissues of 34 patients by real-time PCR. Protein levels of ADRB1 and HSL were determined by western blot analysis. beta1-Adrenoceptor (ADRB1) was also detected by immunofluorescence staining. mRNA expressions of both ADRB1 and HSL were approximately 50% elevated selectively in the cachexia group, whereas mRNA levels of the other receptors were unchanged. beta1-Adrenoceptor (ADRB1) protein expression was 1.5-fold increased in cachexia as compared with the cancer controls, and 3-fold increased as compared with nonmalignant controls, and was confirmed as a membrane protein in adipocytes by immunofluorescence. Hormone-sensitive lipase (HSL) protein expression was 2-2.5-fold increased selectively in cachectic patients. There was a positive correlation between the protein expressions of ADRB1 and HSL. As much as approximately 50% of the variations in HSL protein expression could be explained by variations in ADRB1 protein expression. There was a link between ADRB1 protein level and lipolytic rate. Increased ADRB1 expression may account for some of the functional changes of HSL in patients with cancer cachexia.
Assuntos
Caquexia/fisiopatologia , Lipólise/genética , Neoplasias/genética , Receptores Adrenérgicos beta 1/fisiologia , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Idoso , Ácidos Graxos não Esterificados/metabolismo , Feminino , Quinase 3 de Receptor Acoplado a Proteína G/genética , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/cirurgia , Humanos , Lipólise/fisiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/fisiopatologia , Seleção de Pacientes , Reação em Cadeia da Polimerase , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Receptor de Insulina/genética , Receptores Adrenérgicos beta 1/genética , Receptores do Fator Natriurético Atrial/genéticaRESUMO
OBJECTIVE: To investigate the relationship between insulin post-receptor signal transduction and the change of glucose transportation by skeleton muscle after surgical trauma in rats. METHODS: Small intestine bowel resection was performed to establish the surgical trauma model in rats. The content and the phosphorylation state of two key proteins in the insulin signaling pathway: insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB/Akt) in skeletal muscle were measured respectively. The 3H labeled glucose uptake experiment was carried out to evaluate the glucose transportation function in both groups. Finally, the expression and the distribution of glucose transporter 4 (GLUT4) in skeletal muscle were detected respectively. RESULTS: The total content of IRS-1 and PKB/Akt in skeletal muscle in both groups had no difference. The phosphorylation of tyrosine (Tyr) residue of IRS-1 in the operation group was attenuated by 31% (P = 0.018), whereas the phosphorylation of serine (Ser) residue of IRS-1 was significantly enhanced by 63% compared with the control group (P = 0.000). Accordingly, the phosphorylation state of PKB/Akt (activated) was attenuated by 48% in the operation group (P = 0.000). The rate of 2-Deoxy-D-[1-3H] glucose transported by skeletal muscle in the operation group was significantly lower than that in the control group. Both the expressions of GLUT-4 mRNA and the total content of GLUT-4 protein in two groups had no significant difference. But the expression of GLUT4 in the plasma membrane was decreased in the operation group than that in the control group. CONCLUSIONS: Insulin resistance was associated with enhanced Ser phosphorylation of IRS-1, which impaired its interaction with its downstream target PKB/Akt. Such impaired interactions abolished the ability of IRS-1 to undergo insulin-induced Tyr phosphorylation and further propagate the insulin receptor signal. Uncoupling of signal transduction led to decrease in glucose uptake which associated with a defect in insulin-stimulated glucose transport and GLUT-4 translocation.
Assuntos
Glucose/metabolismo , Insulina/metabolismo , Ferimentos e Lesões/metabolismo , Animais , Modelos Animais de Doenças , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Masculino , Músculo Esquelético/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the protective effect of Atrogin-1 gene silencing via RNA interference technique on a model of muscle cell malnutrition. METHODS: Sequences of five target Atrogin-1 siRNA and the control were selected and synthesized and cloned to vector pBS-hU6-I and then to vector FG12. The length and rightness of the sequences were confirmed. The recombinant FG12 vectors were cotransfected along with pRSVREV, pMDLg/pRRE and pHCMV-G into 293T cells to package lentivirus particles, with which C2C12 cells were infected. The infected C2C12 cells were cultured and differentiated to form myotubes before TNF-alpha was added to induce malnutrition. Expressed products of Atrogin-1 of myotubes were identified by real time PCR and Western blot methods. Myotubes were observed and photographed directly in culture plate without fixation. RESULTS: The length and sequences of inserted DNA were right. Compared with the RNA interferencing group, significant atrophy and upregulated expression of Atrogin-1 of myotubes treated by TNF-alpha was found in the control group. CONCLUSION: Atrogin-1 gene silencing could be used to inhibit malnutrition of muscle cells caused by TNF-alpha. Atrogin-1 could be an ideal target in the treatment of cancer cachexia.
Assuntos
Células Musculares , Proteínas Musculares/genética , RNA Interferente Pequeno/genética , Proteínas Ligases SKP Culina F-Box/genética , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Inativação Gênica , Vetores Genéticos , Lentivirus/genética , Camundongos , Células Musculares/citologia , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Transfecção , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Cyclin D2/D3 (CCND2/3) are core components of the machinery that drives cell cycle progression and therefore, are associated with tumorigenesis. Currently, there are contradictory evidences on the function of CCND2/3 in tumorigenesis. Thus, we conducted a comprehensive meta-analysis to derive a precise predictive value of CCND2/3 in various tumors. We searched PubMed, EMBASE, Web of Science for eligible studies up to October 8, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated using Forest plot analysis to demonstrate their associations. A total of 14 studies were ultimately included in this meta-analysis. Our results indicated CCND2/3 played an oncogenic role in all of the cancer patients (CCND2: pooled HR = 2.21, 95% CI: 1.67-2.93; CCND3: pooled HR = 2.29, 95% CI: 1.05-5.03). In tumor subgroup, CCND2 was associated with shorter OS in patients with gastric cancer (HR = 2.20, 95% CI: 1.66-2.92), whereas it might be a tumor suppressor in NSCLC (HR = 0.28, 95% CI: 0.12-0.64). In addition, CCND3 was correlated to reduced OS in breast cancer patients (HR = 1.64, 95% CI: 1.07-2.52) and shorter DFS/PFS/RFS in bladder cancer patients (HR = 4.60, 95% CI: 1.89-12.57). Taken together, CCND2/3 could be the promising biomarkers for predicting the prognosis of patients with malignant neoplasms.
Assuntos
Biomarcadores Tumorais , Ciclina D2/genética , Ciclina D3/genética , Neoplasias/etiologia , Neoplasias/metabolismo , Ciclina D2/metabolismo , Ciclina D3/metabolismo , Bases de Dados Genéticas , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Modelos de Riscos Proporcionais , Viés de PublicaçãoRESUMO
OBJECTIVE: To demonstrate the changes of resting energy expenditure (REE), substrate metabolism and body composition in cancer patients. METHODS: From September 2004 to March 2008, REE, carbohydrate oxidation (CO) and fat oxidation (FO) in 936 cancer patients and 840 control subjects were measured by indirect calorimetry. Bioelectrical impedance appliance was applied to assess intracellular fluid, extracellular fluid, fat mass (FM) and fat free mass (FFM) in the two groups. RESULTS: No difference in REE was found between the cancer patients and non-cancer patients [(1452.2 +/- 196.4) kcal/d vs. (1429.5 +/- 182.6) kcal/d, P = 0.136]. But REE/FFM and REE/pREE were elevated in cancer patients than in controls (all P < 0.05). Of the cancer patients, 48.6% were hypermetabolic, 42.9% normal and 8.5% hypometabolic, while those were 22.5%, 58.5% and 19.0% in controls. Cancer patients had higher FO [(77.8 +/- 11.3) g/min vs. (67.1 +/- 12.1) g/min, P = 0.000], lower CO and npRQ [(68.7 +/- 10.5) g/min vs. (88.8 +/- 12.1) g/min, P = 0.000; 0.782 +/- 0.012 vs. 0.810 +/- 0.014, P = 0.000]. Cancer patients exhibited lower FM and FFM [(14.9 +/- 4.5) kg vs. (18.4 +/- 5.2) kg, P = 0.000; (44.4 +/- 7.2) kg vs. (46.1 +/- 8.1) kg, P = 0.008]. CONCLUSIONS: Elevated REE is common in cancer patients. Substrate metabolism of the cancer patients features in increased FO, decreased CO and npRQ, which is correlated with the elevated REE. FM and FFM loses in proportion in cancer patients.
Assuntos
Neoplasias/metabolismo , Composição Corporal , Metabolismo dos Carboidratos , Metabolismo Energético , Gorduras/metabolismo , Feminino , Humanos , MasculinoRESUMO
BACKGROUND AND OBJECTIVES: A prior meta-analysis showed favorable metabolic effects of structured triglyceride (STG) lipid emulsions in surgical and critically ill patients compared with mixed medium-chain/long-chain triglycerides (MCT/LCT) emulsions. Limited data on clinical outcomes precluded pharmacoeconomic analysis. We performed an updated meta-analysis and developed a cost model to compare overall costs for STGs vs MCT/LCTs in Chinese hospitals. METHODS AND STUDY DESIGN: We searched Medline, Embase, Wanfang Data, the China Hospital Knowledge Database, and Google Scholar for clinical trials comparing STGs to mixed MCT/LCTs in surgical or critically ill adults published between October 10, 2013 and September 19, 2015. Newly identified studies were pooled with the prior studies and an updated meta-analysis was performed. A deterministic simulation model was used to compare the effects of STGs and mixed MCT/LCT's on Chinese hospital costs. RESULTS: The literature search identified six new trials, resulting in a total of 27 studies in the updated meta-analysis. Statistically significant differences favoring STGs were observed for cumulative nitrogen balance, pre- albumin and albumin concentrations, plasma triglycerides, and liver enzymes. STGs were also associated with a significant reduction in the length of hospital stay (mean difference, -1.45 days; 95% confidence interval, -2.48 to -0.43; p=0.005) versus mixed MCT/LCTs. Cost analysis demonstrated a net cost benefit of ¥675 compared with mixed MCT/LCTs. CONCLUSIONS: STGs are associated with improvements in metabolic function and reduced length of hospitalization in surgical and critically ill patients compared with mixed MCT/LCT emulsions. Cost analysis using data from Chinese hospitals showed a corresponding cost benefit.
Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Emulsões Gordurosas Intravenosas/economia , Nutrição Parenteral/economia , Triglicerídeos/administração & dosagem , Triglicerídeos/economia , China , Farmacoeconomia , HumanosRESUMO
INTRODUCTION: New generations of parenteral lipid emulsions combine Long Chain Triglycerides (LCTs) with Medium Chain Triglycerides (MCTs) either by physically mixing MCT- and LCT-containing oils or by using synthetically structured triglycerides (STGs). In order to clarify some open issues relating to their comparative effect, in particular in terms of clinical outcomes, pertinent evidence was systematically identified, reviewed and meta-analyzed. METHODS: PubMed, Scopus, Wanfang Data, China Hospital Knowledge Database and Google Scholar were searched for published clinical trials comparing STGs vs. MCTs/LCTs PN regimens administered over 5-7 days in surgical and/or critically ill patients. Two independent investigators performed screening and data extraction using a predefined list of parameters. Data were pooled using RevMan® 5.2. Quality of evidence was assessed according to Cochrane's risk of bias tool. Pre-specified high quality (HQ), incremental analyses and a post hoc subgroup analysis were performed. RESULTS: 21 studies were included. The meta-analysis revealed a significantly better cumulative nitrogen balance (Std. mean difference [95% CI]) (1.34 [0.98-1.7], p < 0.00001), as well as higher values for pre-albumin (24.99 mg/L [6.71-43.27], p < 0.000001), and albumin (1.22 g/L [0.66-1.77] p < 0.0001), while plasma triglycerides were significantly lower (-0.28 mmol/L [-0.41 to -0.15], p < 0.0001) in the STG vs. MCT/LCT group. ALT, AST, and GGT were significantly lower with STGs than with MCTs/LCTs, while for total bilirubin and ALP only a trend was observed. STGs were also associated with a trend to a shorter hospital length of stay (LOS) (-1.74 days [-3.49 to 0.01] p = 0.05). Quality of evidence was affected by an unclear risk of selection bias, mostly due to the lack of detailed reporting (random sequence generation, allocation concealment). For the other domains, most of the weighted information was judged at low risk of bias. HQ estimated effects, incremental and subgroup analyses were consistent with the main analysis. CONCLUSIONS: In postsurgical and/or critically ill patients, the administration of STGs vs. MCT/LCTs was significantly associated with improved protein economy, better liver tolerance and a more efficient triglyceride elimination. With regard to clinical outcomes a strong trend towards reduced LOS was observed for STG patients.
Assuntos
Estado Terminal/terapia , Nutrição Parenteral , Triglicerídeos/administração & dosagem , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bases de Dados Factuais , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Medição de Risco , Resultado do Tratamento , Triglicerídeos/químicaRESUMO
AIM: To investigate the potential role of perioperative nutrition in reducing complications and mortality in malnourished gastrointestinal cancer patients. METHODS: Four hundred and sixty-eight elective moderately or severely malnourished surgical patients with gastric or colorectal cancers defined by the subjective global assessment (SGA) were randomly assigned to 7 d preoperative and 7 d postoperative parenteral or enteral nutrition vs a simple control group. The nutrition regimen included 24.6+/-5.2 kcal /kg per d non-protein and 0.23+/-0.04 g nitrogen /kg per d. Control patients did not receive preoperative nutrition but received 600+/-100 kcal non-protein plus or not plus 62+/-16 g crystalline amino acids postoperatively. RESULTS: Complications occurred in 18.3% of the patients receiving nutrition and in 33.5% of the control patients (P=0.012). Fourteen patients died in the control group and 5 in those receiving nutrition. There were significant differences in the mortality between the two groups (2.1% vs 6.0%, P=0.003). The total length of hospitalization and postoperative stay of control patients were significantly longer (29 vs 22 d, P=0.014) than those of the studied patients (23 vs 12 d, P=0.000). CONCLUSION: Perioperative nutrition support is beneficial for moderately or severely malnourished gastrointestinal cancer patients and can reduce surgical complications and mortality.
Assuntos
Desnutrição/terapia , Apoio Nutricional , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Nutrição Enteral , Feminino , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Nutrição Parenteral , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgiaRESUMO
Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss. In vitro cell experiments indicated that loss of Mfn2 was associated with atrophy of the C2C12 mouse myoblast cell line. Furthermore, in vivo animal experiments demonstrated that cachexia decreased gastrocnemius muscle mass and Mfn2 expression, and overexpression of Mfn2 in gastrocnemius muscle was able to partially attenuate cachexia-induced gastrocnemius muscle loss. The results of the present study suggested that Mfn2 is involved in cachexia-induced muscle loss and may serve as a potential target for therapy of cachexia.
RESUMO
OBJECTIVE: To estimate prevalence of malnutrition on admission to hospital and the relationship between nutritional status and prognosis. METHODS: Four thousand and twelve patients admitted to general surgery department were evaluated by a lot of nutrition indexes within 48 h. Operative morbidity and complications were recorded to identify the difference between malnourished and well-nourished patients. RESULTS: Malnutrition rate of all patients according to BMI, TSF, MAC, AMC, albumin, prealbumin, and lymphocyte count was 21.3%, 50.6%, 20.5%, 21.2%, 24.2%, 35.4% and 55.8%, respectively. The prevalence of malnutrition as defined by SGA and MNA were 38.8% and 20.8%. The older patients (> 60 years old) were associated with a higher prevalence of malnutrition (47.6%) compared with those younger than 60 (31.5%). Malnutrition was more frequently occurred in cancer patients than non-oncologic patients (64.5% vs 22.4%). Patients with digestive tract disease had higher rates of malnutrition than those without digestive tract disease (52.6% vs 30.0%). There were large differences in the morbidity and complications between well nourished patients and malnourished patients (4.0% vs 1.1%, P < 0.01 for morbidity; 19.8% vs 5.9% for complications). CONCLUSIONS: The prevalence of malnutrition in hospitalized surgical patients is high. Malnutrition was associated with increased length of stay, higher operative morbidity and complications.
Assuntos
Distúrbios Nutricionais/epidemiologia , Estado Nutricional , Procedimentos Cirúrgicos Operatórios/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , PrognósticoRESUMO
BACKGROUND AND OBJECTIVES: Clinical evidence supports the use of omega-3 polyunsaturated fatty acid (PUFA)-enriched lipid emulsions in place of standard lipid emulsions in parenteral nutrition (PN) for intensive care unit (ICU) patients, but uptake may be limited by higher costs. We compared clinical and economic outcomes for these two types of lipid emulsion in the Chinese ICU setting. METHODS: We developed a pharmacoeconomic discrete event simulation model, based on efficacy data from an international meta-analysis and patient characteristics, resource consumption, and unit costs from a Chinese institutional setting. Probabilistic sensitivity analyses were undertaken to assess the effects of uncertainty around input parameters. Model predictive validity was assessed by comparing results with data observed in a patient subset not used in the modeling. RESULTS: The model predicted that omega-3 PUFA-enriched emulsion (Omegaven(®) 10% fish oil emulsion) would dominate standard lipid emulsions, with better clinical outcomes and lower overall health care costs (mean savings ~10,000 RMB), mainly as a result of faster recovery and shorter hospital stay (by ~6.5 days). The external validation process confirmed the reliability of the model predictions. CONCLUSION: Omega-3 PUFA-enriched lipid emulsions improved clinical outcome and decreased overall costs in Chinese ICU patients requiring PN.