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1.
Paediatr Anaesth ; 34(2): 130-137, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37788105

RESUMEN

INTRODUCTION: Emergence delirium is a common postoperative neurological complication in children after general anesthesia. There is no valid tool to predict emergence delirium. Wavelet index, pain threshold index, anxiety index, and comfort index are real-time brain status parameters extracted from the electroencephalogram, which have recently been developed. The aim is to evaluate the association between real-time brain status parameters during emergence and emergence delirium in children undergoing general anesthesia. METHODS: One hundred and thirty patients between 3 and 6 years of age undergoing dental surgery under general anesthesia were enrolled in the study. Real-time electroencephalogram data were recorded at four different time points from end of anesthetics administration (T1), end of surgery (T2), extubation (T3), and response (eye opening, movement) to verbal stimulation (T4). Each patient was assessed for emergence delirium using the Pediatric Anesthesia Emergence Delirium scale. Receiver operating characteristics curves and the associated areas under the curves were computed to analyze the ability of wavelet index, pain threshold index, anxiety index, and comfort index to predict emergence delirium. RESULTS: One hundred and sixteen patients were included for final analysis. During recovery from general anesthesia, brain status parameters increased significantly from T1 (wavelet index, 59.5 ± 6.2; pain threshold index, 61.7 ± 5.3; anxiety index, 9.2 ± 2.5; comfort index, 21.6 ± 8.7) to T4 (wavelet index, 67.4 ± 9.4; pain threshold index, 73.2 ± 9.1; anxiety index, 38.6 ± 11.2; comfort index, 66.1 ± 16.5; p < .001). To predict emergence delirium, areas under the curves [95% CI] for anxiety index were 0.84 [0.75-0.93] (p < .001), and comfort index was 0.89 [0.81-0.96] (p < .001). The Pediatric Anesthesia Emergence Delirium scale scores of 37 patients were higher than 10 indicating emergence delirium, and the incidence of emergence delirium was 31.90%. The sensitivity and specificity of anxiety index with corresponding cutoff values in predicting emergence delirium were 73.0% and 89.9%, and the sensitivity and specificity of comfort index in predicting emergence delirium were 91.9% and 83.5%. The best cutoff values for anxiety index and comfort index to predict emergence delirium were 46.5 and 68.5, respectively. The areas under the curves [95% CI] of wavelet index to predict emergence delirium were 0.43 [0.31-0.35] (p = .27), while the areas under the curves [95% CI] of pain threshold index to predict emergence delirium were 0.49 [0.37-0.62] (p = .73). DISCUSSION: Both anxiety index and comfort index derived from electroencephalogram wavelet analysis were associated with emergence delirium in pediatric patients undergoing general anesthesia for dental surgery. Wavelet index and pain threshold index were not associated with emergence delirium during general anesthesia for dental surgery in children. CONCLUSIONS: AnXi and CFi might be used to guide anesthesiologists to identify and intervene ED in children.


Asunto(s)
Delirio del Despertar , Niño , Humanos , Delirio del Despertar/epidemiología , Anestesia General/efectos adversos , Complicaciones Posoperatorias , Estudios Prospectivos , Encéfalo , Periodo de Recuperación de la Anestesia
2.
Ecotoxicol Environ Saf ; 281: 116643, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38925033

RESUMEN

Selenium (Se) pollution is mainly caused by anthropogenic activities, and the resulting biosecurity concerns have garnered significant attention in recent years. Using one-compartmental toxicokinetic (TK) modelling, this study explored the kinetic absorption, sub-tissue distribution, and elimination processes of the main Se species (selenate, Se(VI)) in the cultivated aerobic soil of the earthworm Eisenia fetida. The bio-accessibility of earthworm-derived Se was assessed using an in vitro simulated gastrointestinal digestion test to evaluate its potential trophic risk. The results demonstrated that Se accumulated in the pre-clitellum (PC) and total tissues (TT) of earthworms in a time- and dose-dependent manner. The highest Se levels in the PC, post-clitellum (PoC), and TT were 70.54, 57.93, and 64.26 mg/kg during the uptake phase, respectively. The kinetic Se contents in the earthworms PC and TT were consistent with the TK model but not with PoC. The earthworm TT exhibited a faster uptake (Kus = 0.83-1.02 mg/kg/day) and elimination rate of Se (Kee = 0.044-0.049 mg/kg/day), as well as a shorter half-life time (LT1/2 = 15.88-14.22 days) than PC at low soil Se levels (≤5 mg/kg). Conversely, the opposite trend was observed with higher Se concentrations (10 and 20 mg/kg). These results are likely attributable to the tissue specificity and concentration of the toxicant. Earthworms PC and TT exhibited a higher kinetic Se accumulation factor (BAFk) than steady-state BAF (BAFss), with values ranging from 8 to 24 and 3-13, respectively. Furthermore, the bio-accessibility of earthworm-derived Se to poultry ranged from 66.25 % to 84.35 %. As earthworms are at the bottom of the terrestrial food chain, the high bio-accessibility of earthworm-derived Se poses a potential risk to predators. This study offers data support and a theoretical foundation for understanding the biological footprint of soil Se and its toxicological impacts and ecological hazards.

3.
J Gastroenterol Hepatol ; 37(3): 518-530, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34907602

RESUMEN

BACKGROUND AND AIM: Patients undergoing abdominal surgery can develop postoperative ileus (POI). Inflammation of the intestinal muscularis following intestinal manipulation may be caused by displaced bacteria or lipopolysaccharide (LPS). The aim of this study was to investigate the relationship between gut microbiota, LPS, and POI in colorectal cancer (CRC) patients and explore underlying mechanisms of LPS-triggered POI. METHODS: Sixty CRC patients undergoing colorectal resection were included. Bacterial communities from fecal samples were characterized by 16S rRNA gene sequencing, and fecal LPS levels were determined by Limulus amebocyte lysate assay. Mice were used to mechanistically investigate the causal relationship between microbiota, LPS, and POI. RESULTS: We discovered that CRC patients who developed prolonged POI (PPOI) had a unique pro-inflammatory gut microbial composition during the perioperative period. The highest proportions of Gram-negative bacteria at the genus level were Escherichia-Shigella and Bacteroides; the abundance of Escherichia-Shigella was higher throughout the perioperative period. Fecal LPS levels were significantly higher in patients with PPOI. In mice treated with an antibiotic cocktail, intestinal muscularis inflammation and intestinal dysfunction were significantly improved. Inflammation and dysfunction were significantly reduced in mice treated with polymyxin B, but were worsened by treatment with LPS. Moreover, LPS upregulated p38 phosphorylation in mice, and treatment with an inhibitor of p38 (SB203580) significantly alleviated intestinal inflammation and dysmotility. CONCLUSION: Lipopolysaccharide increases intestinal muscularis inflammation via activation of p38 signaling, which aggravates POI. Removing bacterial sources of LPS during the perioperative period is promising for the prophylactic treatment of PPOI.


Asunto(s)
Neoplasias Colorrectales , Ileus , Lipopolisacáridos , Complicaciones Posoperatorias , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Neoplasias Colorrectales/cirugía , Humanos , Ileus/patología , Inflamación , Lipopolisacáridos/metabolismo , Ratones , Complicaciones Posoperatorias/etiología , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
4.
J Gastroenterol Hepatol ; 37(9): 1756-1767, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35849493

RESUMEN

BACKGROUND AND AIMS: Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown. METHODS: We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S-rRNA-based next-generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism. RESULTS: Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-ß/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF-ß/Smad-induced EMT in vitro and in vivo. CONCLUSIONS: Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-ß/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.


Asunto(s)
Microbioma Gastrointestinal , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/etiología , Animales , Colágeno/metabolismo , Colon/metabolismo , Colon/cirugía , Células Epiteliales/metabolismo , Ratas , Factor de Crecimiento Transformador beta
5.
Int J Cancer ; 144(11): 2728-2745, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30565661

RESUMEN

The aim of our study was to investigate the relationship among the gut microbiota community, metabolite profiles and thyroid carcinoma (TC). First, 30 TC patients and 35 healthy controls (HCs) fecal samples were applied to characterize the gut microbial community using 16S rRNA gene sequencing. Differential microbiota compositions were observed, with significant enrichment of 19 and depletion of 8 genera in TC samples compared to those in HCs (Q value <0.05), and some genera were correlated with various clinical parameters, such as lipoprotein A and apolipoprotein B. Furthermore, 6 different genera distinguished TC patients from HCs with the AUC of 0.94. The PICRUSt analysis showed 12 remarkably different metabolic pathways (Q value <0.05). Subsequently, we systematically analyzed the gut microbiota and metabolites in the same TC patients (n = 15) and HCs (n = 15). The characteristics of the gut microbiota community were mostly consistent with the above results (30 TC patients and 35 HCs), and liquid chromatography mass spectrometry analysis was performed to characterize the metabolite profiles. In total, 21 different genera (Q value <0.05) and 72 significantly changed metabolites (VIP > 1.0 and p < 0.05) were observed and correlated to each other. Eight metabolites combined with 5 genera were more effective in distinguishing TC patients from HCs (AUC = 0.97). In conclusion, our study presents a comprehensive landscape of the gut microbiota and metabolites in TC patients, and provides a research direction of the mechanism of interaction between gut microbiota alteration and TC pathogenesis.


Asunto(s)
Heces/microbiología , Microbioma Gastrointestinal/fisiología , Mucosa Intestinal/metabolismo , Cáncer Papilar Tiroideo/microbiología , Neoplasias de la Tiroides/microbiología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , ADN Bacteriano/aislamiento & purificación , Femenino , Voluntarios Sanos , Humanos , Mucosa Intestinal/microbiología , Masculino , Metabolómica , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología
6.
Environ Microbiol ; 21(2): 772-783, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30548192

RESUMEN

Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non-invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.


Asunto(s)
Bacterias/aislamiento & purificación , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/cirugía , Microbioma Gastrointestinal , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/clasificación , Bacterias/genética , Femenino , Humanos , Intestinos/microbiología , Masculino , Persona de Mediana Edad , Adulto Joven
7.
Cell Physiol Biochem ; 47(2): 641-653, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29794468

RESUMEN

BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is a malignant tumor that is resistant to chemotherapy, so new therapeutic agents are needed. Allicin which is rapidly converted from allin by allinase, is one of the most biologically active compounds in freshly crushed garlic and has been shown to have strong anti-tumor effects. Our aim was to explore the molecular mechanism by which allicin affects the cell proliferation and invasion of CCA. METHODS: Cell viability and apoptosis were measured using the CCK-8 assay, colony formation assay, and flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell assays, respectively. The expression of several proteins involved in cell apoptosis and invasion were assessed by Western blot. The activation of STAT3 signaling was detected by Western blot and immunofluorescence staining. The involvement of SHP-1 was determined using small interfering RNA (siRNA). Moreover, a nude mouse model of human CCA was established to assess the anti-tumor effects of allicin in vivo. RESULTS: Allicin significantly suppressed CCA cell proliferation by activating the caspase cascade, inducing apoptosis, and reducing the expression of proteins downstream of STAT3, such as B-cell lymphoma 2 (Bcl-2), while upregulating Bcl-2-associated X (Bax) protein. In addition, allicin inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. Moreover, the protein expression of MMP-2 and MMP-9 was significantly downregulated in CCA cells treated with allicin compared with CCA cells treated with control. Mechanistic investigations indicated that allicin upregulated SHP-1 expression in CCA, and pervanadate treatment reversed the allicin-induced downregulation of STAT3. Moreover, suppression of SHP-1 by siRNA overturned the effect of allicin on the induction of SHP-1 and inhibition of STAT3 activation. Additionally, treatment with allicin attenuated tumor growth in the nude mouse model of CCA. CONCLUSIONS: Our findings suggest that allicin suppresses cell proliferation and invasion via STAT3 signaling and may be a potential therapeutic agent for CCA.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Ácidos Sulfínicos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Disulfuros , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Desnudos , Proteína Tirosina Fosfatasa no Receptora Tipo 6/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/genética , Ácidos Sulfínicos/química , Ácidos Sulfínicos/metabolismo , Ácidos Sulfínicos/uso terapéutico , Trasplante Heterólogo
8.
Tumour Biol ; 37(6): 7657-65, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26687759

RESUMEN

RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/farmacología , Apoptosis/genética , Neoplasias del Colon/tratamiento farmacológico , Fluorouracilo/farmacología , Proteínas de Neoplasias/fisiología , Proteínas de Unión al ARN/fisiología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Apoptosis/efectos de los fármacos , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Reparación del ADN/efectos de los fármacos , Resistencia a Antineoplásicos , Femenino , Células HCT116 , Histonas/biosíntesis , Histonas/genética , Humanos , Masculino , MicroARNs/fisiología , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , ARN Neoplásico/fisiología , Proteínas de Unión al ARN/biosíntesis , Proteínas de Unión al ARN/genética , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Método Simple Ciego
10.
J Pharmacol Exp Ther ; 349(3): 417-26, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24676878

RESUMEN

Intestinal adhesion, characterized by connection of the loops of the intestine with other abdominal organs by fibrous tissue bands, remains an inevitable event of abdominal operations and can cause a number of complications. Berberine hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal medicine, is characterized by diverse pharmacological effects, such as anticancer and lower elevated blood glucose. This study is designed to investigate the effects of berberine on adhesion and inflammation after abdominal surgeries and the underlying molecular mechanisms. Adhesion severity grades and collagen deposition were assessed 14 days after surgery. We evaluated the levels of intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin-1ß (IL-1ß), IL-6, transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α), and examined transforming growth factor-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling. The surgery group experienced the most severe adhesions, and berberine strikingly reduced the density and severity of adhesion. Results showed significant lower expression of IL-1ß, IL-6, TGF-ß, TNF-α, and ICAM-1, in berberine groups compared with the operation group. Activities of phosphorylated JNK and phosphorylated NF-κB were inhibited in the berberine groups compared with the surgery group. Our novel findings identified berberine hydrochloride as a promising strategy to prevent adhesion by downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and TAK1/NF-κB signaling after abdominal surgery, which brought out a good therapeutic approach for the development of clinical application for postoperative abdominal adhesion and inflammation.


Asunto(s)
Antiinflamatorios/uso terapéutico , Berberina/uso terapéutico , Enfermedades Intestinales/prevención & control , Complicaciones Posoperatorias/prevención & control , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Berberina/administración & dosificación , Berberina/química , Modelos Animales de Enfermedad , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Enfermedades Intestinales/inmunología , Enfermedades Intestinales/metabolismo , Masculino , Estructura Molecular , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/metabolismo , Ratas , Ratas Sprague-Dawley , Adherencias Tisulares/inmunología , Adherencias Tisulares/metabolismo , Adherencias Tisulares/prevención & control , Factor de Crecimiento Transformador beta/inmunología , Factor de Necrosis Tumoral alfa/inmunología
11.
Int J Biol Macromol ; 258(Pt 2): 129037, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38158061

RESUMEN

The present work systematically investigated the influence of starch silylation on the structures and properties of starch/epoxidized soybean oil-based bioplastics. Silylated starch was synthesized using starch particles (SP-ST) or gelatinized starch (SG-ST) under different silane hydrolysis pHs. Due to the appearance of -NH2 groups and lower OH wavenumbers, SP-ST obtained at pH 5 showed higher silylation degree and stronger hydrogen bond interaction with epoxidized soybean oils (ESO) than that at pH 11. The morphology analysis revealed better interfacial compatibility of ESO and SP-ST. The tensile strength of the samples containing SP-ST increased by 51.91 % than the control, emphasizing the enhanced interaction within the bioplastics. However, tensile strength of the bioplastics with SG-ST decreased by 59.56 % due to their high moisture contents from unreacted silanes. Additionally, the bioplastics with SG-ST exhibited an obvious reduction of thermal stability and an increase in water solubility because of the presence of unreacted APMS. The bioplastic degradation was not prevented by starch silylation except high pH. The bioplastics showed the most desirable tensile properties, thermal stability, and water solubility when starch was surface-modified with silanes hydrolyzed at pH 5. These outcomes made the fabricated bioplastics strong candidates for petroleum-based plastics for packaging applications.


Asunto(s)
Aceite de Soja , Almidón , Aceite de Soja/química , Almidón/química , Silanos , Agua/química
12.
Free Radic Biol Med ; 220: 125-138, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38657754

RESUMEN

Fusobacterium (F.) nucleatum is a carcinogenesis microbiota in colorectal cancer (CRC). Growing evidence shows that F. nucleatum contributes to chemoresistance. Ferroptosis is reported to restore the susceptibility of resistant cells to chemotherapy. However, the role of gut microbiota affecting ferroptosis in chemoresistance remains unclear. Here, we examined the CRC tissues of patients using 16S rRNA sequencing to investigate the possible connection between gut microbiota dysbiosis and the relapse of CRC. We found that a high abundance of F. nucleatum in CRC tissue is associated with relapse. We further demonstrated that F. nucleatum induced oxaliplatin resistance in vitro and in vivo. The transcriptome of an F. nucleatum-infected cell revealed ferroptosis was associated with F. nucleatum infection. We perform malondialdehyde, ferrous iron, and glutathione assays to verify the effect of F. nucleatum on ferroptosis under oxaliplatin treatment in vivo and in vitro. Mechanistically, F. nucleatum promoted oxaliplatin resistance by overexpressing GPX4 and then inhibiting ferroptosis. E-cadherin/ß-catenin/TCF4 pathway conducted the GPX4 overexpression effect of F. nucleatum. The chromatin immuno-precipitation quantitative PCR (CHIP-qPCR) and dual-luciferase reporter assay showed that F. nucleatum promoted TCF4 binding with GPX4. We also determined the E-cadherin/ß-catenin/TCF4/GPX4 axis related to tumor tissue F. nucleatum status and CRC relapse clinically. Here, we revealed the contribution of F. nucleatum to oxaliplatin resistance by inhibiting ferroptosis in CRC. Targeting F. nucleatum and ferroptosis will provide valuable insight into chemoresistance management and may improve outcomes for patients with CRC.


Asunto(s)
Cadherinas , Neoplasias Colorrectales , Resistencia a Antineoplásicos , Ferroptosis , Fusobacterium nucleatum , Microbioma Gastrointestinal , Oxaliplatino , Fosfolípido Hidroperóxido Glutatión Peroxidasa , beta Catenina , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Cadherinas/metabolismo , Cadherinas/genética , Oxaliplatino/farmacología , beta Catenina/metabolismo , beta Catenina/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Animales , Fusobacterium nucleatum/patogenicidad , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Antígenos CD/metabolismo , Antígenos CD/genética , Femenino , Línea Celular Tumoral , Infecciones por Fusobacterium/microbiología , Infecciones por Fusobacterium/tratamiento farmacológico , Infecciones por Fusobacterium/metabolismo , Infecciones por Fusobacterium/genética , Infecciones por Fusobacterium/patología , Disbiosis/microbiología , Factor de Transcripción 4/metabolismo , Factor de Transcripción 4/genética , Ratones Desnudos
13.
Aging (Albany NY) ; 15(21): 12413-12450, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37938164

RESUMEN

BACKGROUND: Evidence suggests that the tumor microenvironment (TME) affects the tumor active response to immunotherapy. Tumor angiogenesis is closely related to the TME. Nonetheless, the effects of angiogenesis on the TME of colorectal cancer (CRC) remain unknown. METHODS: We comprehensively assessed the angiogenesis patterns in CRC based on 36 angiogenesis-related genes (ARGs). Subsequently, we evaluated the prognostic values and therapeutic sensitivities of angiogenesis patterns using multiple methods. We then performed the machine learning algorithm and functional experiments to identify the prognostic key ARGs. Ultimately, the regulation of gut microbiota on the expression of ARGs was further investigated by using whole genome sequencing. RESULTS: Two angiogenesis clusters were identified and angiogenesis cluster B was characterized by increased stromal and immunity activation with unfavorable odds of survival. Further, an ARG_score including 9 ARGs to predict recurrence-free survival (RFS) was established and its predominant predictive ability was confirmed. The low ARG_score patients were characterized by a high mutation burden, high microsatellite instability, and immune activation with better prognosis. Moreover, patients with high KLK10 expression were associated with a hot tumor immune microenvironment, poorer immune checkpoint blocking treatment, and shorter survival. The in vitro experiments also indicated that Fusobacterium nucleatum (F.n) infection significantly induced KLK10 expression in CRC. CONCLUSIONS: The quantification of angiogenesis patterns could contribute to predict TME characteristics, prognosis, and individualized immunotherapy strategies. Furthermore, our findings suggest that F.n may influence CRC progression through ARGs, which could serve as a clinical biomarker and therapeutic target for F.n-infected CRC patients.


Asunto(s)
Neoplasias Colorrectales , Inmunoterapia , Humanos , Pronóstico , Algoritmos , Fenómenos Fisiológicos Cardiovasculares , Fusobacterium nucleatum , Microambiente Tumoral/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia
14.
Carbohydr Polym ; 300: 120253, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36372510

RESUMEN

In this work, a systematic coupling study of silane coupling agent between starch and epoxidized soybean oils (ESO) was carried out. Starch was modified by 3-aminopropyl trimethoxy silane (APMS) with various contents of NaOH. The APMS-modified starch was incorporated with ESO to synthesize the bioplastics by solution casting. As demonstrated by the FTIR spectra, the hydrogen bond interactions among starch molecules were inhibited by the modification. This outcome provided higher interaction and compatibility of starch with ESO, as confirmed by FESEM. TGA showed that the thermal stability of starch decreased considerably after the silylation. In contrast, the produced bioplastics with silylated starch exhibited higher thermal stability than the control sample. Regarding the bioplastics, an obvious increase of tensile strength from 5.78 MPa to 9.29 MPa was obtained. This work suggested a simple and effective modification technique by APMS to improve compatibility of starch/ESO-based bioplastics with superior mechanical and thermal properties.


Asunto(s)
Manihot , Aceite de Soja , Aceite de Soja/química , Manihot/química , Silanos , Almidón/química , Resistencia a la Tracción
15.
Front Cell Infect Microbiol ; 12: 1022603, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36389160

RESUMEN

Anastomotic leak (AL) is a life-threatening postoperative complication following colorectal surgery, which has not decreased over time. Until now, no specific risk factors or surgical technique could be targeted to improve anastomotic healing. In the past decade, gut microbiota dysbiosis has been recognized to contribute to AL, but the exact effects are still vague. In this context, interpretation of the mechanisms underlying how the gut microbiota contributes to AL is significant for improving patients' outcomes. This review concentrates on novel findings to explain how the gut microbiota of patients with AL are altered, how the AL-specific pathogen colonizes and is enriched on the anastomosis site, and how these pathogens conduct their tissue breakdown effects. We build up a framework between the gut microbiota and AL on three levels. Firstly, factors that shape the gut microbiota profiles in patients who developed AL after colorectal surgery include preoperative intervention and surgical factors. Secondly, AL-specific pathogenic or collagenase bacteria adhere to the intestinal mucosa and defend against host clearance, including the interaction between bacterial adhesion and host extracellular matrix (ECM), the biofilm formation, and the weakened host commercial bacterial resistance. Thirdly, we interpret the potential mechanisms of pathogen-induced poor anastomotic healing.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Disbiosis/microbiología , Anastomosis Quirúrgica/efectos adversos , Recto/microbiología , Fuga Anastomótica/microbiología , Neoplasias Colorrectales/complicaciones
16.
Front Genet ; 13: 947747, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36246627

RESUMEN

Despite recent advances in surgical and multimodal therapies, the overall survival (OS) of advanced colorectal cancer (CRC) patients remains low. Thus, discerning sensitive prognostic biomarkers to give the optimistic treatment for CRC patients is extremely critical. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play an important role in CRC progression. Nonetheless, few studies have focused on the impact of m6A-related lncRNAs on the prognosis, tumor microenvironment (TME) and treatment of CRC. In this study, 1707 m6A-related lncRNAs were identified through Pearson correlation analysis and Weighted co-expression network analysis (WGCNA) using The Cancer Genome Atlas (TCGA) cohort. Then, 28 m6A-related prognostic lncRNAs were screened by univariate Cox regression analysis, followed by identifying two clusters by consensus clustering analysis. A prognostic model consisted of 8 lncRNA signatures was constructed by the least absolute shrinkage and selection operator (LASSO). Kaplan-Meier curve analysis and a nomogram were performed to investigate the prognostic ability of this model. The risk score of prognostic model act as an independent risk factor for OS rate. Functional enrichment analysis indicated that lncRNA signatures related tumor immunity. The low-risk group characterized by increased microsatellite instability-high (MSI-H), mutation burden, and immunity activation, indicated favorable odds of OS. Moreover, the lncRNA signatures were significantly associated with the cancer stem cell (CSC) index and drug sensitivity. In addition, 3 common immune genes shared by the lncRNA signatures were screened out. We found that these immune genes were widely distributed in 2 cell types of TME. Finally, a ceRNA network was constructed to identify ZEB1-AS1 regulatory axis in CRC. We found that ZEB1-AS1 was significantly overexpressed in tumor tissues, and was related to the metastasis of EMT and the chemoresistance of 5-Fu in CRC. Therefore, our study demonstrated the important role of m6A-related lncRNAs in TME remodeling. Moreover, these results illustrated the levels of ZEB1-AS1 might be valuable for predicting the progression and prognosis of CRC, and further provided a new target for the diagnosis and treatment of CRC patients.

17.
Spectrochim Acta A Mol Biomol Spectrosc ; 278: 121359, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-35569199

RESUMEN

Solar driven water splitting for hydrogen generation has been considered as an important method for collecting clean energy. Herein, based on first-principles calculations, we propose that ZnO/BlueP van der Waals heterostructure can realize overall water splitting reaction for hydrogen generation. Strikingly, the band-gap of 1.83 eV is appropriate, and band alignments straddle the water redox potentials, ensuring the occurrence of hydrogenevolutionreaction and oxygen evolution reaction. Charge density distribution and carrier mobility exhibit significant charge separation and transfer. Visible-light response is improved compared with those of the isolated monolayers. Moreover, hydrogenevolutionreaction is actually realized on the ZnO layer, while oxygen evolution reaction is implemented on the BlueP layer. Through the investigation of the adsorption and dissociation reactions of H2O, we observe that two neighboring H*s prefer to combine to form H2 by overcoming a lowered energy barrier of 0.75 eV. Strain effect indicates that the lateral compressive strain of -4% to 0% and the vertical tensile strain of 0% to +6% can effectively tune band-gap and band alignments. The results indicate that ZnO/BlueP vdW heterostructure is probable highly efficient photoelectric material used for visible-light driven water splitting for hydrogen generation.

18.
Chemosphere ; 287(Pt 3): 132277, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34826938

RESUMEN

Microbial fuel cells (MFCs) are sensitive to acidity variations in both bioelectricity generation and biochemical digestion aspects, therefore online pH monitoring is of necessity to guarantee optimal function of MFCs. Present pH meters hardly fulfill this special need. In this work, we designed a novel voltammetric pH sensor based on electrochemically reduced graphene oxide (rGO) modified screen printed electrode. By surface doping of alizarin, good linearity of pH sensing over the range of 4.0-9.0 can be realized. Fast readout can be acquired within 15 s for each test. pH monitoring for artificial wastewater with inoculum of granular activated sludge in a MFC was successfully illustrated. Specially, it was verified that the performance was improved with alizarin doping due to the enhanced rGO surface proton diffusion. This approach provides an online, calibration-free and long stable pH monitoring method for the future MFC development.


Asunto(s)
Fuentes de Energía Bioeléctrica , Grafito , Nanocompuestos , Antraquinonas , Electrodos , Concentración de Iones de Hidrógeno
19.
Front Genet ; 13: 925338, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35937993

RESUMEN

Background: Abnormal mucosal inflammation is a critical risk factor for pathogenesis and progression of colorectal cancer (CRC). As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in CRC remains unclear. Methods: A total of 38 pyroptosis-related gene (PRG) expression profiles and clinical information were collected from multiple public datasets. Bioinformatics methods were used to analyze the clinical significance, functional status, immune infiltration, genomic alteration, and drug sensitivity in different subgroups. Whole-genome microarray analysis was performed to analyze the regulation of gut microbiota on the expression of PRGs. Results: Two distinct molecular subtypes were identified and suggested that multilayer PRG alterations were associated with patient clinicopathological features, prognosis, and tumor microenvironment (TME) infiltrating characteristics. Furthermore, we obtained eight PRG signatures by applying differential expression analysis and univariate Cox and Lasso regression analyses. A risk prognosis model was constructed for predicting overall survival (OS) and recurrence-free survival (RFS) based on the PRG signature. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high- and low-risk groups. In addition, the PRG signature was significantly associated with the microsatellite instability (MSI), tumor mutation burden (TMB), cancer stem cell (CSC) index, immunotherapeutic characteristics, and chemotherapeutic drug sensitivity. Moreover, the in vitro experiments had shown that Fusobacterium nucleatum (F.n) could affect the CASP6 expression, which was associated with the chemoresistance to 5-fluorouracil (5-Fu) in CRC. Conclusion: Our findings provided a foundation for future research targeting pyroptosis and a new insight into the prognosis and immune cell infiltration of CRC, and they suggested that F.n might influence CRC progression through pyroptosis.

20.
Chemosphere ; 286(Pt 3): 131943, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34426266

RESUMEN

The wide use of chloramphenicol and its residues in the environments are an increasing threat to human beings. Electroactive microorganisms were proven with the ability of biodegradation of chloramphenicol, but the removal rate and efficiency need to be improved. In this study, a model electricigens, Geobacter metallireducens, was supplied with and Fe3O4 and MnO2 nanoparticles. Five times higher chloramphenicol removal rate (0.71 d-1) and two times higher chloramphenicol removal efficiency (100%) was achieved. Fe3O4 and MnO2 nanoparticles highly increased the current density and NADH-quinone oxidoreductase expression. Fe3O4 nanoparticles enhanced the expression of alcohol dehydrogenase and c-type cytochrome, while MnO2 nanoparticles increased the transcription of pyruvate dehydrogenase and Type IV pili assembly genes. Chloramphenicol was reduced to a type of dichlorination reducing product named CPD3 which is a benzene ring containing compound. Collectively, Fe3O4 and MnO2 nanoparticles increased the chloramphenicol removal capacity in MFCs by enhancing electron transfer efficiency. This study provides new enhancing strategies for the bioremediation of chloramphenicol in the environments.


Asunto(s)
Geobacter , Nanopartículas del Metal , Cloranfenicol , Geobacter/genética , Humanos , Compuestos de Manganeso , Oxidación-Reducción , Óxidos
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