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1.
Mol Cancer ; 23(1): 124, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849840

RESUMO

BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.


Assuntos
Progressão da Doença , Glicogênio Sintase Quinase 3 beta , Metaplasia , Cadeias Pesadas de Miosina , beta Catenina , Humanos , Metaplasia/metabolismo , Metaplasia/patologia , Metaplasia/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Animais , beta Catenina/metabolismo , beta Catenina/genética , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Feminino , Via de Sinalização Wnt , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Modelos Animais de Doenças , Masculino , Organoides/metabolismo , Organoides/patologia
2.
Biomacromolecules ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39315891

RESUMO

Quercetin (QR) is a natural flavonoid with strong anti-inflammatory properties, but it suffers from poor water solubility and bioavailability. Micro/nanomotors (NMs) are tiny devices that convert external energy or chemical fuels into an autonomous motion. They are characterized by their small size, rapid movement, and self-assembly capabilities, which can enhance the delivery of bioactive ingredients. The study synthesized natural polysaccharide-based nanotubes (NTs) using a layer-by-layer self-assembly method and combined with urease (Ure), glucose oxidase (GOx), and Fe3O4 to create three types of NMs. These NMs were well-dispersed and biocompatible. In vitro experiments showed that NMs-Fe3O4 has excellent photothermal conversion properties and potential for use in photothermal therapy. Cellular inflammation model results demonstrated that QR-loaded NMs were not only structurally stable but also improved bioavailability and effectively inhibited the release of inflammatory mediators such as IL-1ß and IL-6, providing a safe and advanced carrier system for the effective use of bioactive components in food.

3.
Entropy (Basel) ; 25(4)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37190467

RESUMO

This paper investigates lift, the likelihood ratio between the posterior and prior belief about sensitive features in a dataset. Maximum and minimum lifts over sensitive features quantify the adversary's knowledge gain and should be bounded to protect privacy. We demonstrate that max- and min-lifts have a distinct range of values and probability of appearance in the dataset, referred to as lift asymmetry. We propose asymmetric local information privacy (ALIP) as a compatible privacy notion with lift asymmetry, where different bounds can be applied to min- and max-lifts. We use ALIP in the watchdog and optimal random response (ORR) mechanisms, the main methods to achieve lift-based privacy. It is shown that ALIP enhances utility in these methods compared to existing local information privacy, which ensures the same (symmetric) bounds on both max- and min-lifts. We propose subset merging for the watchdog mechanism to improve data utility and subset random response for the ORR to reduce complexity. We then investigate the related lift-based measures, including ℓ1-norm, χ2-privacy criterion, and α-lift. We reveal that they can only restrict max-lift, resulting in significant min-lift leakage. To overcome this problem, we propose corresponding lift-inverse measures to restrict the min-lift. We apply these lift-based and lift-inverse measures in the watchdog mechanism. We show that they can be considered as relaxations of ALIP, where a higher utility can be achieved by bounding only average max- and min-lifts.

4.
Entropy (Basel) ; 24(1)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35052135

RESUMO

This paper studies how to attain fairness in communication for omniscience that models the multi-terminal compress sensing problem and the coded cooperative data exchange problem where a set of users exchange their observations of a discrete multiple random source to attain omniscience-the state that all users recover the entire source. The optimal rate region containing all source coding rate vectors that achieve omniscience with the minimum sum rate is shown to coincide with the core (the solution set) of a coalitional game. Two game-theoretic fairness solutions are studied: the Shapley value and the egalitarian solution. It is shown that the Shapley value assigns each user the source coding rate measured by their remaining information of the multiple source given the common randomness that is shared by all users, while the egalitarian solution simply distributes the rates as evenly as possible in the core. To avoid the exponentially growing complexity of obtaining the Shapley value, a polynomial-time approximation method is proposed which utilizes the fact that the Shapley value is the mean value over all extreme points in the core. In addition, a steepest descent algorithm is proposed that converges in polynomial time on the fractional egalitarian solution in the core, which can be implemented by network coding schemes. Finally, it is shown that the game can be decomposed into subgames so that both the Shapley value and the egalitarian solution can be obtained within each subgame in a distributed manner with reduced complexity.

5.
Gastrointest Endosc ; 99(6): 1075, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38762303
6.
J Surg Res ; 228: 93-99, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907236

RESUMO

BACKGROUND: Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. MATERIALS AND METHODS: The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. RESULTS: The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. CONCLUSIONS: Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations.


Assuntos
Anti-Infecciosos Locais/efeitos adversos , Neoplasias Colorretais/cirurgia , Lavagem Peritoneal/efeitos adversos , Povidona-Iodo/efeitos adversos , Choque Séptico/induzido quimicamente , Acidose/induzido quimicamente , Acidose/diagnóstico , Animais , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacocinética , Azoximetano/toxicidade , Translocação Bacteriana/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Sulfato de Dextrana/toxicidade , Endotoxinas/sangue , Endotoxinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/cirurgia , Absorção Peritoneal , Lavagem Peritoneal/métodos , Permeabilidade/efeitos dos fármacos , Povidona-Iodo/administração & dosagem , Povidona-Iodo/farmacocinética , Ratos , Ratos Sprague-Dawley , Choque Séptico/sangue , Choque Séptico/diagnóstico , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/ultraestrutura
8.
Inorg Chem ; 53(14): 7446-54, 2014 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-24967909

RESUMO

A variety of network structures have been prepared by transmetalation of a polymer {Na3[Na9(Cbdcp)6(H2O)18]}n (1) (Cbdcp = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium) containing dodecahedral Na9 aggregate secondary building units with Cu(II) by modulating the temperature, solvent, and pH. These complexes include a large, zwitterionic hexa-cuprometallocycle [Cu6(Cbdcp)6(H2O)18] (2) formed in H2O at room temperature, two three-dimensional polymers [Cu3(Cbdcp)2(OH)2(H2O)2]n (3) and {[Cu3(Cbdcp)2(OH)2]·2H2O}n (4) isolated from H2O and DMF/H2O at 135 °C, and a mononuclear complex [Cu(HCbdcp)2(H2O)3]·H2O (5) from H2O at 100 °C and pH = 6. All the complexes are robust and water stable. The crystal framework of macrocycle 2 is stable up to 100 °C under vacuum and selectively adsorbs CO2.


Assuntos
Cobre/química , Polímeros/química , Sódio/química , Cristalografia por Raios X , Modelos Moleculares , Água/química
9.
Angew Chem Int Ed Engl ; 53(18): 4628-32, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24692130

RESUMO

A 2D coordination polymer prepared with bulky diethylformamide solvates exhibits channels which allow dipyridyl bridging ligands to diffuse into the crystal lattice. The absorbed dipyridyls thread through the pores of one layer and substitute the surface diethylformamide molecules on the neighboring layers to stitch alternate layers to form flexible interpenetrated metal-orgaic frameworks. The threading process also results in exchange of the bulky diethylformamide solvates for aqua to minimize congestion and, more strikingly, forces the slippage of two-dimensional layers, while still maintaining crystallinity.


Assuntos
Cádmio/química , Compostos Organometálicos/química , Polímeros/química , 2,2'-Dipiridil/química , Dióxido de Carbono/química , Cristalografia por Raios X , Dimetilformamida/análogos & derivados , Dimetilformamida/química , Modelos Moleculares , Nitrogênio/química
10.
PLoS One ; 19(9): e0310096, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39283881

RESUMO

OBJECTIVE: Prewarming has been recommended to reduce intraoperative hypothermia. However, the evidence is unclear. This review examined if prewarming can prevent intraoperative hypothermia in patients undergoing thoracoscopic and laparoscopic surgeries. METHODS: PubMed, CENTRAL, Web of Science, and Embase databases were searched for randomized controlled trials (RCTs) up to 15th January 2024. The primary outcome of interest was the difference in intraoperative core temperature. The secondary outcomes were intraoperative hypothermia (<36°) and postoperative shivering. RESULTS: Seven RCTs were eligible. Meta-analysis showed that intraoperative core temperature was significantly higher at the start or within 30mins of the start of the surgery (MD: 0.32 95% CI: 0.15, 0.50 I2 = 94% p = 0.0003), 60 mins after the start of the surgery (MD: 0.37 95% CI: 0.24, 0.50 I2 = 81% p<0.00001), 120 mins after the start of the surgery (MD: 0.34 95% CI: 0.12, 0.56 I2 = 88% p = 0.003), and at the end of the surgery (MD: 0.35 95% CI: 0.25, 0.45 I2 = 61% p<0.00001). The incidence of shivering was also significantly lower in the prewarming group (OR: 0.18 95% CI: 0.08, 0.43 I2 = 0%). Prewarming was also associated with a significant reduction in the risk of hypothermia (OR: 0.20 95% CI: 0.10, 0.41 I2 = 0% p<0.0001). The certainty of the evidence assessed by GRADE was "moderate" for intraoperative core temperatures at all time points and "low" for minimal intraoperative core temperature, shivering, and hypothermia. CONCLUSION: Moderate to low-quality evidence shows that prewarming combined with intraoperative warming, as compared to intraoperative warming alone, can improve intraoperative temperature control and reduce the risk of hypothermia and shivering in patients undergoing thoracoscopic and laparoscopic procedures.


Assuntos
Abdome , Hipotermia , Humanos , Hipotermia/prevenção & controle , Hipotermia/etiologia , Abdome/cirurgia , Laparoscopia/métodos , Complicações Intraoperatórias/prevenção & controle , Complicações Intraoperatórias/epidemiologia , Estremecimento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Cuidados Intraoperatórios/métodos , Procedimentos Cirúrgicos Torácicos/métodos , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Temperatura Corporal
11.
Adv Healthc Mater ; 12(27): e2301243, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37463303

RESUMO

The mortality rate of sepsis remains high despite improvements in the diagnosis and treatment of sepsis using symptomatic and supportive therapies, such as anti-infection therapy and fluid resuscitation. Nucleic acid-based drugs have therapeutic potential, although their poor stability and low delivery efficiency have hindered their widespread use. Herein, it is confirmed that miR-223 can polarize proinflammation M1 macrophages to anti-inflammation M2 macrophages. A pH-sensitive nano-drug delivery system comprising ß-cyclodextrin-poly(2-(diisopropylamino)ethyl methacrylate)/distearoyl phosphoethanolamine-polyethylene glycol (ß-CD-PDPA/DSPE-PEG) is synthesized and developed to target M1 macrophages and miR-223 is encapsulated into nanoparticles (NPs) for sepsis treatment. NPs/miR-223 demonstrated in vitro pH responsiveness with favorable biosafety, stability, and high delivery efficiency. In vivo studies demonstrate that NPs/miR-223 are preferentially accumulated and retained in the inflammation site, thereby reducing inflammation and improving the survival rate of mice with sepsis while exhibiting ideal biosafety. Mechanically, NPs/miR-223 regulates macrophage polarization by targeting Pknox1 and inhibiting the activation of the NF-κB signaling pathway, thereby achieving an anti-inflammatory effect. Collectively, it is demonstrated that the miRNA delivery vector described here provides a new approach for sepsis treatment and accelerates the advancement of nucleic acid drug therapy.


Assuntos
Ciclodextrinas , MicroRNAs , Sepse , Animais , Camundongos , MicroRNAs/genética , Macrófagos/metabolismo , Inflamação/metabolismo , Sepse/tratamento farmacológico , Sepse/metabolismo , Concentração de Íons de Hidrogênio , Proteínas de Homeodomínio/metabolismo
12.
ACS Appl Mater Interfaces ; 15(17): 20697-20711, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37083309

RESUMO

Conventional chemotherapy usually fails to achieve its intended effect because of the poor water solubility, poor tumor selectivity, and low tumor accumulation of chemotherapy drugs. The systemic toxicity of chemotherapy agents is also a problem that cannot be ignored. It is expected that smart nano-drug delivery systems that are able to respond to tumor microenvironments will provide better therapeutic outcomes with decreased side effects of chemotherapeutics. Nano-drug delivery systems capable of breaking the redox balance can also increase the sensitivity of tumor cells to chemotherapeutics. In this study, using polymer-containing disulfide bonds, ester bonds, and d-α-tocopherol polyethylene glycol succinate (TPGS), which can amplify reactive oxygen species (ROS) in tumor cells, we have successfully prepared a smart glutathione (GSH) and esterase dual-responsive nano-drug delivery system (DTX@PAMBE-SS-TPGS NPs) with the ability to deplete GSH as well as amplify ROS and effectively release an encapsulated chemotherapy drug (DTX) in tumor cells. The potential of DTX@PAMBE-SS-TPGS NPs for enhanced antitumor effects was thoroughly evaluated using in vitro as well as in vivo experiments. Our research offers a promising strategy for maximizing the efficacy of tumor therapy.


Assuntos
Antineoplásicos , Nanopartículas , Sistemas de Liberação de Fármacos por Nanopartículas , Espécies Reativas de Oxigênio , Nanopartículas/química , Antineoplásicos/química , Glutationa/metabolismo , Oxirredução , Linhagem Celular Tumoral
13.
Nutrients ; 15(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38140350

RESUMO

BACKGROUND AND AIMS: The efficacy and underlying mechanisms of exclusive enteral nutrition (EEN) in adult patients with Crohn's disease (CD) remain controversial. This study aimed to evaluate the role of EEN in adult patients with CD and to explore the mechanisms from the perspective of immunoregulation. METHODS: This is a prospective, open-label pilot study. Active patients with CD were enrolled and prescribed an amino-acid-rich elemental diet for 12 weeks. Dynamic changes in immune cells, including neutrophils, monocytes, T cells and B cells, were detected by flow cytometry. Plasma cytokines were evaluated by ELISA. RESULTS: Twenty adult patients with CD were enrolled. Among them, 1 discontinued treatment due to poor compliance, and 19 patients were included for final analysis. Clinical remission was achieved in 47.37% (9/19), 63.16% (12/19), and 73.68% (14/19) patients at weeks 4, 8, and 12, respectively. Endoscopic remission and transmural healing were achieved in 52.63% (10/19) and 15.79% (3/19) patients at week 12. Notably, there was no significant difference in clinical remission between week 4 and week 8 (p = 0.33) or week 12 (p = 0.09). Furthermore, we observed a rapid reconstitution of immunologic homeostasis as early as week 4. At week 4, both the frequency and activation of neutrophils and monocytes were decreased after EEN therapy. Significant decreases in Th17 cells and naïve B cells, increases in memory B cells, and regulatory B cells were also detected. These changes remained stable at weeks 8 and 12. CONCLUSIONS: EEN with an amino-acid-rich elemental diet orchestrated immunological balances and induces clinical remission in adult CD patients as early as week 4, suggesting a 4-week EEN therapy may be feasible and practicable in clinical practice.


Assuntos
Doença de Crohn , Adulto , Humanos , Doença de Crohn/terapia , Nutrição Enteral , Estudos Prospectivos , Projetos Piloto , Indução de Remissão
14.
Transpl Immunol ; 74: 101660, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35787932

RESUMO

BACKGROUND: Sepsis in patients is a great threat to human health due to its high incidence rate, its rapid and unpredictable progression, as well as it is difficult to treat, and it has poor prognosis. Ferroptosis is a newly discovered type of cell death characterized by the iron-dependent peroxide aggregation. Furthermore, ferroptosis is different from other forms of cell death, namely apoptosis, necrosis, pyroptosis and autophagy. Our study investigated the role of ferroptosis-related genes in sepsis. METHODS: The GSE65682 dataset from the Gene Expression Omnibus (GEO) database was used to screen ferroptosis-related genes associated with sepsis, and the GSE134347 dataset for the external validation of selected hub genes. The univariate Cox regression analysis, Kaplan-Meier (K-M) survival analysis and weighted gene co-expression network analysis (WGCNA) were used to identify hub genes. Evaluation of the immune cell infiltration in sepsis was used to explain the immune heterogeneity among the cell subtypes. Gene set variation analysis (GSVA) and transcriptional regulatory analysis of selected hub genes further elucidated the probable mechanism of ferroptosis-related genes associated with prognosis in sepsis. Finally, we constructed a competing endogenous RNA (ceRNA) network model. RESULTS: A total of 479 RNA-seq data points were used for analysis, including 365 samples from patients who survived sepsis and 114 samples from patients who succumbed to sepsis from the available GSE65682 dataset. Consequently, the univariate Cox regression analysis and consensus clustering analysis divide all 479 sepsis samples into two clusters of "survivals" vs. "non-survivals". Following complex analysis were identified as the most important ferroptosis-related genes. Indeed, the WGCNA and K-M analyses associated the expression patterns of NEDD4L and SIAH2 hub genes as the best prognosis for the survival of sepsis (p < 0.05). The expression trend was also consistent with the survival trend of the NEDD4L and SIAH2 hub genes by the external validation of GSE134347 (p < 0.05). Immune cell infiltration analysis indicated that the types and numbers of different immune cells vary among different subtypes and NEDD4L and SIAH2 hub genes. For example, NEDD4L and SIAH2 gene expression had a positive correlation with M0 macrophages and a negative correlation with neutrophils (p > 0.05). Finally, analysis of two hub genes and transcription factors (TFs) showed that 71 TFs were predicted to be related to NEDD4L while 64 TFs to SIAH2 by the Cistrome DB online database. CONCLUSION: We suggest that NEDD4L and SIAH2 hub genes are involved in the ferroptosis-associated sepsis. The pattern of NEDD4L and SIAH2 expression in patients undergoing sepsis may have prognostic potential for the severity of sepsis and eventually for patients' survival.


Assuntos
Ferroptose , Sepse , Apoptose , Ferroptose/genética , Perfilação da Expressão Gênica , Humanos , Prognóstico , Sepse/genética
15.
J Colloid Interface Sci ; 628(Pt B): 864-876, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36029600

RESUMO

Drug delivery based on abnormal features of the tumor microenvironment (TME) has attracted considerable interest worldwide. In this study, we proposed an applicable strategy to increase the reactive oxygen species (ROS) and inhibit glutathione (GSH), in an effort to amplify oxidative damage in prostate cancer cells. Specifically, we developed dual-responsive supramolecular self-assembled nanoparticles (NPs) based on polymerized methacrylic acid (MA) and polymerized poly(ethylene glycol) dimethyl acrylate-modified ß-cyclodextrin (CD) with ferrocene (Fc)-connected (S) (+)-camptothecin (CPT) (designated as MA-CD/Fc-CPT NPs). The as-prepared negatively charged supramolecular NPs can be taken up by tumor cells successfully owing to their reversible negative-to-positive charge transition capacity at acidic pH. The supramolecular NPs increased ROS generation and decreased GSH to amplify oxidative stress and improve the therapeutic effect of chemotherapy. As expected, MA-CD/Fc-CPT NPs displayed good drug delivery capabilities to tumor cells or tissues. MA-CD/Fc-CPT NPs also inhibited cancer cell proliferation in both the cells and tissues. This result was partially due to increased ROS generation and decreased GSH, which contributed to more pronounced oxidative stress. The as-prepared supramolecular NPs displayed great biosafety to normal tissues. According to our results, negatively charged supramolecular MA-CD/Fc-CPT NPs are well-suited for drug delivery and improved cancer treatment in TMEs.


Assuntos
Ciclodextrinas , Nanopartículas , beta-Ciclodextrinas , Masculino , Humanos , Espécies Reativas de Oxigênio , Metalocenos , Nanopartículas/química , Camptotecina/química , Oxirredução , Metacrilatos , Glutationa , Polietilenoglicóis , Linhagem Celular Tumoral
16.
Nutr Clin Pract ; 37(2): 366-376, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34245474

RESUMO

BACKGROUND: Conventional treatment for Crohn disease (CD) in pregnancy includes mesalamine, thiopurine, and anti-tumor necrosis factor (TNF)-α agents. However, women may abstain because of complications, nonresponse, or potential adverse outcomes. Peptide-based formula therapy, through oral or nasogastric feeding without other food intake, is an effective and safe therapy for active CD. Herein, We confirmed the effectiveness and safety of peptide-based formula therapy for active CD in pregnant women or those preparing for pregnancy. METHOD: Outcomes of peptide-based formula therapy to induce CD remission during pregnancy preparation and the conception period were evaluated retrospectively among 14 women. Efficacy was evaluated as the change in serum indices and inflammatory markers after 12-week treatment. Pregnancy outcomes were compared between 14 women treated with nutrition therapy and eight women using conventional CD drugs. RESULTS: After 12 weeks, 85.7% (12 of 14) of patients treated with peptide-based formula achieved remission with a significant decrease in the CD activity index (P < .001) and high-sensitivity C-reactive protein level (P = .004). There were no effects of peptide-based formula therapy on pregnancy outcomes compared with conventional CD treatment (P > .05). Among the 12 patients who achieved CD remission with exclusive peptide-based formula therapy, 10 selected to continue total or partial peptide-based formula treatment to maintain CD remission throughout pregnancy. CONCLUSION: Peptide-based formula therapy, without other food intake, may provide a safe and effective alternative to conventional CD drugs to induce disease remission among women during conception and pregnancy.


Assuntos
Doença de Crohn , Doença de Crohn/tratamento farmacológico , Nutrição Enteral , Feminino , Humanos , Peptídeos/uso terapêutico , Gravidez , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
17.
J Immunother Cancer ; 10(12)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36600557

RESUMO

BACKGROUND: As an integral part of the tumor microenvironment (TME), tumor-associated neutrophils play a crucial role in tumor development. The objective of this study was to investigate the plasticity of tumor-associated N1 and N2 neutrophils in the TME of pancreatic ductal adenocarcinoma (PDAC), along with its impact on survival and association with immune infiltrations. METHODS: The primary and validation cohorts including 90 radical resection patients from September 2012 to May 2016 and 29 radical resection patients from September 2018 to October 2019, respectively, with complete survival data, were enrolled. Immunofluorescence staining was used to identify tumor-associated N1 and N2 neutrophils, and the N1/N2 ratio was used to evaluate N1 and N2 plasticity. Thereafter, the association between tumor-associated N1/N2 neutrophil plasticity, clinical features, and immune infiltrations was investigated. RESULTS: There was a significant increase in tumor-associated N2 neutrophils compared with tumor-associated N1 neutrophils. Low N1/N2 ratios were associated with the poorer differentiation of tumors, easier lymph node metastases, and a higher TNM stage. The median overall survival (OS) and recurrence-free survival (RFS) of the high tumor-associated N1 neutrophil group were significantly longer than those of the low group, while the tumor-associated N2 neutrophils played an opposite role. The multivariable analysis revealed that a high N1/N2 ratio was a significant prognostic indicator for OS and RFS. In addition, tumor-associated N1/N2 neutrophils showed an opposite correlation with tumor-infiltrating CD8+ T cells and Tregs. CONCLUSION: The plasticity of tumor-associated N1/N2 neutrophils was identified as a crucial prognostic indicator that might reflect the TME and immune escape in patients with PDAC. On further investigation and validation, our findings may be used to further stratify patients with varying prognoses to optimize treatment.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Prognóstico , Neutrófilos/patologia , Linfócitos T CD8-Positivos/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/cirurgia , Pâncreas/patologia , Microambiente Tumoral , Neoplasias Pancreáticas
18.
Aliment Pharmacol Ther ; 55(7): 764-777, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35141914

RESUMO

BACKGROUND: Ustekinumab is effective in treating Crohn's disease (CD) and ulcerative colitis (UC). However, the loss of response (LOR) to ustekinumab and the efficacy of dose escalation have not been systematically explored. METHODS: Databases were searched for eligible studies from inception through July 2021. Summary estimates were pooled, and subgroup analyses were performed to explore heterogeneity. RESULTS: We included 14 studies (CD: 13; UC: 1). In CD patients, the annual risk of LOR to ustekinumab and dose escalation among primary responders was 21% (95% confidence interval [CI] 12-31%, 1530 person-years, n = 9) per person-year and 25% (95% CI 12-32%, 657 person-years, n = 5) per person-year respectively. Clinical response was regained in 58% (95% CI 49-67%, 279 patients, n = 8) of secondary non-responders after dose escalation (interval reduction or intravenous reinduction). In UC patients, no studies provided data on LOR, but only one study showed that 35% (100/284) of patients underwent dose escalation (or sham dose adjustment), leading to an annual risk of dose escalation of 18% per person-year. After dose escalation, 58% (14/24) of the patients regained symptomatic remission. CONCLUSIONS: Primary responders with CD experienced LOR to ustekinumab at a risk of 21% per person-year and required dose escalation at a risk of 25% per person-year. Fifty-eight per cent of secondary non-responders with CD may benefit from dose escalation. LOR has not been well characterized in patients with UC.


Assuntos
Doenças Inflamatórias Intestinais , Ustekinumab , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ustekinumab/administração & dosagem
19.
Poult Sci ; 98(10): 4401-4407, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31041437

RESUMO

Preserved egg, a traditional Chinese egg product, is regarded as an anti-inflammatory food in traditional Chinese medicine. This study was aimed to examine anti-inflammatory effect of the simulated gastrointestinal digestive products of whole preserved egg (DWPE), preserved egg white (DPEW), and preserved egg yolk (DPEY) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results demonstrated that DWPE, DPEW, or DPEY inhibited the LPS-induced secretion of Nitric oxide (NO), without marked cytotoxicity. The DWPE, DPEW, and DPEY significantly suppressed the secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. Particularly, the inhibition rate of DPEW on NO, IL-6, and TNF-α could reach 25 to 27%, 31 to 42%, and 26 to 38%, respectively (P < 0.05). Furthermore, the DPEW and DPEY downregulated the gene expression of Cyclooxygenase-2 and inducible nitric oxide synthase in a dose-dependent manner. Taken together, this study indicated that DWPE, DPEW, and DPEY, especially DPEW, might serve as functional food for anti-inflammatory therapy.


Assuntos
Anti-Inflamatórios/farmacologia , Clara de Ovo/química , Gema de Ovo/química , Inflamação/tratamento farmacológico , Óvulo/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Ovos/análise , Medicina Tradicional Chinesa , Camundongos , Células RAW 264.7
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