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1.
Curr Gene Ther ; : e060224226738, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38682449

RESUMO

INTRODUCTION: Crohn's disease (CD) and colorectal cancer (CRC) represent a group of intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal immune homeostasis. Therefore, comprehending the immune response mechanisms in both categories of intestinal disorders is of paramount significance in the prevention and treatment of these debilitating intestinal ailments. METHOD: IIn this study, we conducted single-cell analysis on paired samples obtained from primary colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the factors influencing the composition of the intestinal immune microenvironment. By aligning T cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell, and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T cells in both syndromes to delineate their differentiation patterns and identify key driver genes Result: Furthermore, cellular communication and transcription factor regulatory networks are all essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The identified complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC. CONCLUSION: Finally, the analysis of regulon networks revealed several promising candidates for cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in CD and CRC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-37305690

RESUMO

Objective: To explore the role of Huangqin Decoction in intestinal homeostasis maintenance and colon carcinogenesis based on "sterol regulatory element binding protein-1c (SREBP-1)-cholesterol metabolism regulatory T cell (Treg) differentiation." Methods: It was decided to utilize a total of 50 healthy Wistar rats for the study, 20 of which were chosen at random to serve as controls, and 30 of which were used to create an intestinal homeostasis imbalance model. It was determined whether or not the modeling was successful by killing 10 rats from each of the two groups. The remaining 10 rats in the normal group were then employed as the control group for the experiment. The random number table method was used to split the rats into two groups: the Huangqin Decoction (n = 10) and the Natural Recovery (n = 10) groups. For seven days, participants in the Huangqin Decoction group received the herb, whereas those in the natural healing group received normal saline. The relative density of SREBP1, the levels of cholesterol ester (CE), free cholesterol (FC), total cholesterol (TC), and Treg cells were detected and compared. Results: When compared to the control group, the relative density of SREBP1 increased significantly before administration in the Huangqin Decoction group and the natural recovery group, but decreased significantly after administration, with statistical significance (P < 0.05) in the Huangqin Decoction group and the natural recovery group; the Huangqin Decoction group and natural recovery group had significantly higher levels of CE, FC, and TC than the control group before to administration, and these levels increased significantly after administration. CE, FC, and TC levels in Huangqin Decoction and natural recovery groups were much lower than those in natural recovery groups, and the difference was statistically significant (P < 0.05), according to the results; Prior to administration, Treg cell levels in Huangqin Decoction group and the natural recovery group were significantly higher, and Treg cell levels in the Huangqin Decoction group and natural recovery group were significantly lower after administration; the decrease in the Huangqin Decoction group was significantly greater than that in natural recovery group. P < 0.05 indicated that the difference was significant. Conclusion: Using Huangqin Decoction, one may efficiently regulate SREBP1, cholesterol metabolism, and Treg cell development, all of which play an important role in maintaining intestinal stability and minimizing the incidence of colon cancer.

3.
Front Nutr ; 9: 850063, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694167

RESUMO

Objective: This study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery. Methods: This prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses. Results: According to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002 <3), and the PG-SGA score was identified as a predictor of post-operative infection complications of CRC. Conclusion: The pre-operative nutritional status of patients with GC or CRC has an impact on post-operative infection occurrence. NRS2002 ≥5 was a risk factor for post-operative infection in patients with GC, and the PG-SGA B/C was a predictor of infections in patients with CRC.

4.
Injury ; 53(8): 2754-2762, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35760641

RESUMO

BACKGROUND: Consensus regarding the optimal amount of bone cement and vertebral height in the treatment of osteoporotic vertebral compression fractures (OVCFs) is lacking. Our purpose was to explore the optimal amount of bone cement and vertebral height in OVCF after percutaneous vertebral augmentation (PVA). METHODS: A three-dimensional finite element model of the L1-L3 segments was constructed from CT scans of aging osteoporosis patients. Four different postoperative vertebral height models were simulated according to Genant semiquantitative grades 0, 1, 2, and 3. The volume of bone cement filling ranged from 3 ml to 6 ml. These models evaluated the von Mises stress of injured vertebral bodies, adjacent vertebral bodies and intervertebral discs under flexion, extension, left flexion, and right flexion after PVA. RESULTS: When the bone cement content was held constant, as the height of the vertebral body decreased, the stress of the L2 vertebral body decreased during left flexion and right flexion, but the stress of the L2 vertebral body increased and decreased during flexion and extension. As the height of the vertebral body decreased, the stress of the L1-L2 intervertebral disc increased. There was no significant change in the stress of other adjacent vertebrae or intervertebral discs. When the Genant grade was 0, 1, or 2 (3 ml and 4 ml), the stress of the overall vertebral body was closest to normal. CONCLUSIONS: When the height of the vertebral body is restored to the same height, a bone cement filling volume of 3 ml to 6 ml is suitable and will not produce a significant change in the stress of the vertebral body or adjacent vertebral body. As vertebral body height was lost, it may promote the degeneration of the intervertebral disc above the injury vertebrae after PVA. It is appropriate for the height of the vertebral body to return to Genant grade 0 or Genant grade 1 after surgery. When the height of the vertebral body has Genant grade 2 status, it was best to use 3 ml to 4 ml of bone cement filling. Therefore, when treating OVCFs, clinicians do not need to pursue complete reduction of the vertebral body. It is also important to verify the biomechanics results in clinical studies.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Cimentos Ósseos/uso terapêutico , Análise de Elementos Finitos , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia
6.
JAMA Surg ; 157(5): 384-393, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35293973

RESUMO

Importance: The effect of and optimal timing for initiating supplemental parenteral nutrition (SPN) remain unclear after major abdominal surgery for patients in whom energy targets cannot be met by enteral nutrition (EN) alone. Objective: To examine the effect of early supplemental parenteral nutrition (E-SPN) (day 3 after surgery) or late supplemental parenteral nutrition (L-SPN) (day 8 after surgery) on the incidence of nosocomial infections in patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to EN. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted from April 1, 2017, to December 31, 2018, in the general surgery department of 11 tertiary hospitals in China. Participants were those undergoing major abdominal surgery with high nutritional risk and poor tolerance to EN (≤30% of energy targets from EN on postoperative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) and an expected postoperative hospital stay longer than 7 days. Data analysis was performed from February 1 to October 31, 2020. Interventions: Random allocation to E-SPN (starting on day 3 after surgery) or L-SPN (starting on day 8 after surgery). Main Outcomes and Measures: The primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge. Results: A total of 230 patients (mean [SD] age, 60.1 [11.2] years; 140 men [61.1%]; all patients were of Han race and Asian ethnicity) were randomized (115 to the E-SPN group and 115 to the L-SPN group). One patient in the L-SPN group withdrew informed consent before the intervention. The E-SPN group received more mean (SD) energy delivery between days 3 and 7 compared with the L-SPN group (26.5 [7.4] vs 15.1 [4.8] kcal/kg daily; P < .001). The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (10/115 [8.7%] vs 21/114 [18.4%]; risk difference, 9.7%; 95% CI, 0.9%-18.5%; P = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (31/115 [27.0%] vs 38/114 [33.3%]; risk difference, 6.4%; 95% CI, -5.5% to 18.2%; P = .32), total adverse events (75/115 [65.2%] vs 82/114 [71.9%]; risk difference, 6.7%; 95% CI, -5.3% to 18.7%; P = .32), and rates of other secondary outcomes. A significant difference was found in the mean (SD) number of therapeutic antibiotic days between the E-SPN group and the L-SPN group (6.0 [0.8] vs 7.0 [1.1] days; mean difference, 1.0 days; 95% CI, 0.2-1.9 days; P = .01). Conclusion and Relevance: In this randomized clinical trial, E-SPN was associated with reduced nosocomial infections in patients undergoing abdominal surgery and seems to be a favorable strategy for patients with high nutritional risk and poor tolerance to EN after major abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03115957.


Assuntos
Estado Terminal , Infecção Hospitalar , Estado Terminal/terapia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/etiologia , Infecção Hospitalar/prevenção & controle , Nutrição Enteral , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral
7.
Clin Nutr ; 40(12): 5802-5811, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34775223

RESUMO

BACKGROUND & AIMS: The strategy of increasing the postoperative enteral nutrition dose to the target goal has not yet been clarified. This study aimed to determine whether an immediate goal-dose enteral nutrition (IGEN) strategy is non-inferior to a gradual goal-dose enteral nutrition (GGEN) strategy in reducing infections in patients undergoing abdominal surgery involving the organs of the digestive system. METHODS: This randomized controlled trial enrolled postoperative patients with nutritional risk screening 2002 scores ≥3 from 11 Chinese hospitals. Energy targets were calculated as 25 kcal/kg and 30 kcal/kg of ideal body weight for women and men, respectively. Patients were randomly assigned 1:1 to IGEN or GGEN group after enteral tolerance was confirmed (30% of the target on day 2). The IGEN group immediately started receiving 100% of the caloric requirements on day 3, while the GGEN group received 40% progressing to 80% of target on day 7. The primary endpoint was the infection rate until discharge, based on the intention-to-treat population. RESULTS: A total of 411 patients were enrolled and randomized to the IGEN and GGEN groups, and five patients did not receive the allocated intervention. A total of 406 patients were included in the primary analysis, with 199 and 207 in the IGEN and GGEN groups, respectively. Infection was observed in 17/199 (8.5%) in the IGEN group and 19/207 (9.2%) in the GGEN group, respectively (difference, -0.6%; [95% confidence interval (CI), -6.2%-4.9%]; P = 0.009 for non-inferiority test). There were significantly more gastrointestinal intolerance events with IGEN than with GGEN (58/199 [29.1%] vs. 32/207 [15.5%], P < 0.001). All other secondary endpoints were non-significant. CONCLUSIONS: Among postoperative patients at nutritional risk, IGEN was non-inferior to GGEN in regards to infectious complications. IGEN was associated with more gastrointestinal intolerance events. It showed that IGEN cannot be considered to be clinically directive. ClinicalTrials.gov (#NCT03117348).


Assuntos
Abdome/cirurgia , Infecção Hospitalar/epidemiologia , Nutrição Enteral/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Idoso , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Ingestão de Energia , Nutrição Enteral/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Cuidados Pós-Operatórios/efeitos adversos
8.
Am J Transl Res ; 13(12): 14074-14080, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35035750

RESUMO

OBJECTIVE: To explore the regulation of miR-125a-5p in hepatocellular carcinoma (HCC) and its mechanisms. METHODS: By transfecting a miR-125a-5p sequence and an interfering sequence of miR-125a-5p-s into human HCC cell lines HCC-LM3 and HepG2, miR-125a-5p-related levels were assesed by Western blot. The abilities of cell proliferation and migration were assessed by cell culture and Transwell assay, respectively. RESULTS: HepG2 cells showed increased miR-125a-5p levels compared with HCC-LM3 cells (P < 0.01). However, compared with QZG cells, the level of miR-125a-5p in HepG2 and HCC-LM3 cells was down-regulated. Compared with miR-125a-5p groups, miR-125a-5p-s groups showed increased colony formation rate and mobility (P < 0.01). After being transfected with miR-125a-5p, the transformation factor 2ß (TRA2ß) and mRNA levels were decreased, whereas 5p-s expression was increased (P < 0.01). Inhibition of TRA2ß by small interfering RNA (siRNA) diminished the ability of cells. CONCLUSION: miR-125a-5p inhibits the invasive capacity of HCC cells through targeting the TRA2ß pathway.

9.
Eur J Cancer Prev ; 30(1): 59-68, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33275396

RESUMO

Evidences for the personalized use of nonsteroidal anti-inflammatory drugs (NSAIDs) in colorectal cancer (CRC) prevention and treatment that include consideration of prostaglandin E2 levels are necessary. This study was designed as a case-control study including 60 CRC patients and 120 cancer-free controls. A sensitive empirical method, precolumn derivatization HPLC, was used to determine plasma PGE2 levels. The TaqMan SNP Genotyping Assay was used for the genotyping of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms. Multivariate logistic regression analysis suggested that 1 log10(PGE2) increase would result in a 3.64-fold increase in the risk of CRC. Moreover, subjects with log10(PGE2) level in the 75th percentile had a significantly higher risk of CRC than those with log10(PGE2) levels in the 25th percentile [odds ratio (OR), 3.50; 95% confidence interval (CI), 1.35-9.05]. This association was more evident after adjustment for history of NSAIDs use (OR, 3.85; 95% CI, 1.46-10.16). Preliminarily, 260.02 and 414.95 pg/ml might be proposed as the preventive and warning cutoff values of plasma PGE2 for CRC. The preferred NSAIDs dose for patients with the AG+GG (rs689466) and CC+CT (rs5275) genotypes should be higher than that of patients carrying AA or TT genotypes, despite the presence of equal plasma PGE2 levels. We show for the first time that the plasma PGE2 level is associated with the risk of CRC. We provide a preliminary suggestion for NSAIDs doses adjustment according to PTGS2 genotypes after consideration of plasma PGE2 levels.


Assuntos
Neoplasias Colorretais/sangue , Dinoprostona/sangue , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Casos e Controles , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Ciclo-Oxigenase 2/genética , Feminino , Genótipo , Humanos , Masculino , Polimorfismo Genético , Fatores de Risco
10.
Onco Targets Ther ; 13: 6093-6108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612370

RESUMO

PURPOSE: Numerous metabolomics studies have been conducted to detect the metabolic mechanisms and biomarkers related to gastric cancer and colorectal cancer. Because of the common metabolic features between gastric cancer and colorectal cancer, a differential diagnosis is difficult. Here, we performed a systematic review and meta-analysis to identify differential metabolic biomarkers between these two types of cancers. MATERIALS AND METHODS: PubMed, Embase, and ScienceDirect were searched to identify all metabolomics studies of gastric cancer and colorectal cancer published up to September 2018. Differential metabolites or altered pathways were extracted. The intersections and differences for these metabolites and pathways between gastric cancer and colorectal cancer were compared. Candidate biomarker sets for diagnosis were proposed from biofluid or feces by comparing them with tumor tissues. RESULTS: Totally, 24 and 65 studies were included in gastric cancer and colorectal cancer, and 223 and 472 differential metabolites were extracted, respectively. Eight pathways were reproducibly enriched in blood, tissue and urine in gastric cancer, while, 11 pathways were reproducibly enriched in blood, urine, feces and tissue in colorectal cancer. Candidate metabolic biomarker sets in blood, urine, or feces for these two cancers were proposed. We found 27 pathways (categorized into eight classifications) common to both cancers, five pathways involving 35 metabolites enriched only in gastric cancer, and eight pathways involving 54 metabolites enriched only in colorectal cancer. CONCLUSION: The altered metabolic pathways showed signatures of abnormal metabolism in gastric cancer and colorectal cancer; the potential metabolic biomarkers proposed in this study have important implications for the prospective validation of gastric cancer and colorectal cancer.

11.
Front Oncol ; 10: 981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626659

RESUMO

Background: Colorectal cancer (CRC) is the result of complex interactions between the tumor's molecular profile and metabolites produced by its microenvironment. Despite recent studies identifying CRC molecular subtypes, a metabolite classification system is still lacking. We aimed to explore the distinct phenotypes and subtypes of CRC at the metabolite level. Methods: We conducted an untargeted metabolomics analysis of 51 paired tumor tissues and adjacent mucosa using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Multivariate analysis including principal component analysis, orthogonal partial least squares discriminant analysis and heat maps, univariate analysis, and pathway analysis were used to identify potential metabolite phenotypes of CRC. Unsupervised consensus clustering was used to identify robust metabolite subtypes, and evaluated their clinical relevance. Results: A total of 173 metabolites (including nucleotides, carbohydrates, free fatty acids, and choline) were identified between CRC tumor tissue and adjacent mucosa. We found that lipid metabolism was closely related to the occurrence and progression of CRC. In particular, CRC tissues could be divided into three subtypes, and statistically significant correlations between different subtypes and clinical prognosis were observed. Conclusions: CRC tumor tissue exhibits distinct metabolite phenotypes. Metabolite differences between subtypes may provide a basis and direction for further clinical individualized treatment planning.

12.
Am J Transl Res ; 12(12): 7899-7907, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33437368

RESUMO

Several studies have proved the tumor-suppressive effects of miR-335 but its role in colon cancer via regulation of the Raf/MEK/ERK signalling pathway is yet unknown. As such the main motive of conducting the present study was to elucidate the role of miR-335 in colon cancer via regulation of Raf/MEK/ERK signalling pathway and to explore its therapeutic potential. The results revealed significant (P < 0.05) downregulation of miR-335 in colon cancer and its overexpression led to a significant (P < 0.05) decline in viability of the HT-29 and SW948 cells. The TUNNEL assay showed miR-335 promotes apoptosis in the HT-29 and SW948 colon cancer cells and is also associated with increase in Bax and decrease in Bcl-2 expression. The results also revealed that miR-335 overexpression enhances the sensitivity of the HT-29 and SW948 cells to the apoptotic effects of cisplatin. From the transwell assays, it was found that the migration of the HT-29 and SW948 cells was decreased by 53% and 45% and while as invasion was decreased by 49% and 42% respectively (P < 0.05). Finally, western blot analysis showed that miR-335 blocks the Raf/MEK/ERK signalling pathway in HT-29 colon cancer cells. The results of in vivo study showed that miR-335 also exhibits tumor-suppressive effects on xenografted tumors. Taken together, it is concluded that miR-335 acts as tumor-suppressor in colon cancer and may exhibit therapeutic implications in its treatment.

13.
Gut Liver ; 12(2): 173-182, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29291617

RESUMO

BACKGROUND/AIMS: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. METHODS: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. RESULTS: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. CONCLUSIONS: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.


Assuntos
Neoplasias Colorretais , Metilação de DNA/genética , Leucócitos/metabolismo , Proteínas Mitocondriais/genética , Proteínas do Tecido Nervoso/genética , Proteínas WT1/genética , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Estudos de Casos e Controles , China , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ilhas de CpG/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Interação Gene-Ambiente , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
14.
Oncol Rep ; 38(6): 3545-3553, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29130099

RESUMO

The present study was designed to assess the expression of microRNA-542-3p (miR-542-3p) in human colon cancer and investigate the possible molecular mechanisms underlying the effect of miR-542-3p on the growth and invasion of colon cancer cells. We found that miR-542-3p expression was downregulated in colon cancer patient tissues, compared with that observed in the control group. Silencing of miR­542-3p expression significantly promoted cell viability and inhibited apoptosis. In addition, overexpression of miR-542-3p significantly reduced cell viability and promoted apoptosis in colon cancer cells. Meanwhile, silencing of miR-542-3p expression significantly suppressed PI3K and p-AKT and survivin protein expression, while overexpression of miR-542-3p significantly induced PI3K and p-AKT and survivin protein expression in colon cancer cells. PI3K inhibitor (LY294002) or survivin inhibitor (YM155) suppressed PI3K/AKT/survivin signaling and increased the anticancer effects of miR-542-3p on the apoptosis in colon cancer. The present study demonstrated that upregulation of miR-542-3p inhibited the growth and invasion of colon cancer cells through PI3K/AKT/survivin signaling, highlighting a novel therapeutic approach for the treatment of colon cancer.


Assuntos
Neoplasias do Colo/genética , Proteínas Inibidoras de Apoptose/metabolismo , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Neoplasias do Colo/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Masculino , Morfolinas/farmacologia , Naftoquinonas/farmacologia , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Survivina
15.
Oncotarget ; 8(29): 47379-47388, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28537887

RESUMO

Long-term dietary intake influences the structure and activity of microorganisms residing in the human gut. The immune response and gut microbiota have a mutual influence on the risk of colorectal cancer (CRC). This study examines the association of gut microbiota-related dietary factors and polymorphisms in the microRNA-binding site of the interleukin 13 gene (IL13) with the risk and prognosis of CRC. Three polymorphisms (rs847, rs848, and rs1295685) were selected for genotyping in a case-control study (513 cases, 572 controls), and 386 CRC patients were followed up. Two dietary factors closely related with gut microbiota (allium vegetables, overnight meal) were significantly associated with CRC development. Although the three SNPs showed no statistically significant associations with the risk and prognosis of CRC, a significant antagonistic interaction was found between rs848 (G-T) and allium vegetable intake (ORi (odds ratio of interaction), 0.92; 95% CI (confidence interval): 0.86, 0.99; P = 0.03); moreover, significant combined and synergistic interactions were observed for all three SNPs and overnight meal intake. This is the first report of significant combined and interactive effects between dietary factors and polymorphisms in the microRNA binding site of IL13 in CRC and may provide direct guidance on intake of allium vegetable and overnight meals for individuals with specific genetic variants of IL13 to modify their susceptibility to CRC.


Assuntos
Sítios de Ligação , Neoplasias Colorretais/etiologia , Dieta , Interleucina-13/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Suscetibilidade a Doenças , Feminino , Microbioma Gastrointestinal , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico
16.
Mater Sci Eng C Mater Biol Appl ; 77: 1012-1016, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28531972

RESUMO

Bio-synthesis of Platinum nanoparticles (Pt NPs) was achieved using Mentha piperita (Peppermint) aqueous leaf extract. Further the ecofriendly synthesized Pt NPs were subjected for various characterization techniques. The characterization results inferred that the green synthesized Pt NPs were said to be in average particle size of 54.3nm. The particles are in spherical shape and it has been entrapped with secondary metabolites (Polyphenols). The polyphenols capped Pt NPs were screened for cytotoxicity against human colon cancer cell line (HCT 116). The results inferred that the ecofriendly synthesized Pt NPs decrease the viability of cancer cells at lower concentrations with IC50 value of 20µg/mL.


Assuntos
Neoplasias do Colo , Linhagem Celular Tumoral , Humanos , Mentha piperita , Nanoestruturas , Platina , Polifenóis
17.
Nutr J ; 14: 68, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26170020

RESUMO

BACKGROUND & OBJECTIVE: Nutrition assessment enables early identification of malnourished patients and those at risk of malnutrition. To determine the prevalence of malnutrition, to analyze the correlation between short-form Mini Nutritional Assessment (MNA-SF) and Nutritional Risk Screening 2002 (NRS2002) with classical nutritional markers among elderly hospitalized patients in surgery departments, with a view to improving nutrition advice for these patients. METHODS: A total of 142 elderly patients admitted for surgery were enrolled in the study. Within 48 hours of admission, MNA-SF and NRS2002 scale, anthropometric measures and biochemical tests were carried out to assess the nutritional status of each patient. RESULTS: The prevalence of malnutrition classified by MNA-SF, NRS2002, BMI, serum albumin, hemoglobin, total lymphocyte count, handgrip strength, calf circumference and mid-arm circumference were 45%, 38%, 17%, 22%, 24%, 71%, 36%, 12 % and 15 %, respectively. As the nutritional status classified by both MNA-SF and NRS2002 deteriorated, BMI, serum albumin, hemoglobin, handgrip strength, mid-arm circumference and calf circumference of patients with malnutrition were lower (P < 0.05). MNA-SF and NRS2002 had a unanimous correlation with classical nutritional markers (P < 0.05) except total lymphocyte count (P > 0.05). MNA-SF results showed a moderate agreement (P < 0.001) with NRS2002. Malnourished patients were older than well-nourished patients with NRS2002 (P < 0.05). Digestive disease patients tend to suffer from malnutrition, evaluated by MNA-SF (P < 0.05). CONCLUSIONS: The results show a relatively high prevalence of malnutrition among elderly patients in our general surgery department, especially in patients with digestive disease. NRS2002 and MNA-SF on elderly patients showed great consistency but significant difference in elderly patients with digestive disease. Both MNA-SF and NRS2002 correlated with each other and with BMI, serum albumin, hemoglobin, handgrip strength, calf circumference and mid-arm circumference. MNA-SF may be a more suitable tool for the nutrition assessment of surgical elderly inpatients.


Assuntos
Pacientes Internados , Desnutrição/epidemiologia , Avaliação Nutricional , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Avaliação Geriátrica , Força da Mão , Hemoglobinas/metabolismo , Hospitalização , Humanos , Contagem de Linfócitos , Masculino , Desnutrição/diagnóstico , Estado Nutricional , Prevalência , Albumina Sérica
18.
J Cancer Res Clin Oncol ; 141(9): 1533-44, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25604582

RESUMO

PURPOSE: T lymphocyte immune responses are controlled by both co-stimulatory and co-inhibitory signaling through T cell co-receptors. Cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1) and B and T lymphocyte attenuator (BTLA) are all co-inhibitory molecules that negatively regulate the activation of T cells. In this study, we investigated the relationship between ten tagging SNPs in three co-inhibitory molecule genes and colorectal cancer (CRC). METHODS: We conducted a hospital-based case-control study consisting of 601 cases with CRC and 627 CRC-free individuals from the Heilongjiang Province of China. RESULTS: The rs7421861 CT genotype was significantly associated with the risk of colorectal cancer compared to the wild-type TT genotype (adjusted OR 1.314, 95% CI 1.012-1.706, P = 0.041). The rs2705535 TT genotype was associated with the risk of rectal cancer [OR 1.819 (1.093-3.027), P = 0.021]. There was statistical interaction between the PD-1/rs2227982 (CT + TT) genotypes and high seafood intake (>once/week), as well as the CTLA-4/rs231777 variant and high pungent food intake (>3 times/week). The AG + AA genotypes of CTLA-4/rs3087243 statistically and antagonistically interacted with soybeans, pork and alcohol intake and were associated with CRC risk. Analogously, BTLA/rs1844089 interacted with pork intake, PD-1/rs7421861 with beef and lamb consumption and PD-1/rs6710479 with barbecue consumption. Haplotype G-C-G-A-T-T-A was significantly associated with CRC risk (OR 1.221 P = 0.034). CONCLUSIONS: These data indicate potential associations between BTLA and PD-1 polymorphisms and CRC susceptibility. Additionally, the three co-inhibitory molecule gene SNPs have environmental interactions associated with CRC risk.


Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Receptores Coestimuladores e Inibidores de Linfócitos T/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Estudos de Casos e Controles , Neoplasias Colorretais/imunologia , Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia , Feminino , Predisposição Genética para Doença , Vetores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Adulto Jovem
19.
Med Oncol ; 31(10): 73, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25216863

RESUMO

Limited studies about the effects of TLR 4 and IL17 polymorphisms (SNPs) on the risk of colorectal cancer (CRC) have yielded inconsistent results. Totally, 601 CRC patients and 627 controls were enrolled. Unconditional logistic regression was used to estimate the association between tagSNPs and susceptibility of CRC and the interactions effects of gene and environment on the risk of CRC. IL17 rs6973569 AG and AG/AA genotypes significantly decreased the risk of CRC compared with GG genotype (ORadjusted=0.72, 95% CI 0.55-0.94 and ORadjusted=0.74, 95 % CI 0.57-0.97). The haplotype G-T-G-C-A-G accounting for the largest proportion haplotypes increased the risk of CRC (OR=1.27, 95 % CI 1.06-1.53). However, G-C-C-T-A-G and G-C-G-C-A-G haplotypes decreased the susceptibility of CRC. Synergistic interactions between TLR 4 rs1927911 CT/TT and higher pungent food intake as well as IL17 rs6973569 AG/AA genotypes and higher intake of sausage food (ORi=1.72, 95% CI 1.04-2.84 and ORi=3.38, 95% CI 1.28-8.91) on the risk of CRC were observed. IL17 rs6973569 SNP might be an independent factor of susceptibility to CRC. TLR 4 haplotype of G-T-G-C-A-G may increase risk of CRC. Higher intake of pungent and sausage food synergistically interacted with TLR 4 and IL17 SNPs on the risk of CRC.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-17/genética , Polimorfismo Genético , Receptor 4 Toll-Like/genética , Idoso , Estudos de Casos e Controles , China , Feminino , Genótipo , Haplótipos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
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