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1.
Ann Surg Oncol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739239

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) for radical distal gastrectomy needs to be improved urgently. We investigated the effects of probiotic compounds (including Lactobacillus plantarum, L. rhamnosus, L. acidophilus, and Bifidobacterium animalis subsp.lactis) on enhance recovery after gastrectomy. METHODS: The patients in this prospective study were divided into probiotic group (PG group, n = 36) and placebo group (CG group, n = 38), taking corresponding capsule according to the protocol during the perioperative period. We compared the trends in perioperative hematologic findings and the postoperative outcomes. Patients' feces were collected for bacterial 16S rRNA sequencing. Patients were followed up at 1 month postoperatively. RESULTS: After the application of probiotics, the patients' postoperative inflammatory response level was reduced, and the trend of postoperative NLR decrease was significantly faster in the patients of the PG group than in the CG group (P = 0.047, partial η2 = 0.054). The trend of postoperative increase in serum albumin concentration in the patients of the PG group was significantly better than that in the CG group (P = 0.016, partial η2 = 0.078). In addition, patients in the PG group met discharge criteria earlier postoperatively and had fewer medical expenses. The quality of life of PG group was improved postoperatively. Postoperative inflammation-related markers, including the ratio of Firmicutes/Bacteroidetes, were increasing in untreated patients. In addition, the postoperative microbial diversity and abundance in the PG group remained stable. CONCLUSIONS: Probiotic compounds can reduce the inflammatory response after gastrectomy and enhance the recovery of the DGC patients by maintaining the stability of the gut microbiota.

2.
Int Immunol ; 35(10): 483-495, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37465957

RESUMO

Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.


Assuntos
Lúpus Eritematoso Sistêmico , Monócitos , Humanos , Monócitos/metabolismo , Macrófagos , NF-kappa B/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas de Neoplasias/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
3.
Scand J Gastroenterol ; 59(1): 52-61, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37632275

RESUMO

PURPOSE: The aim of this study was to develop and externally validate a nomogram to accurately predict the overall survival (OS) of patients with gastric adenocarcinoma who underwent radical gastrectomy. MATERIALS AND METHODS: A total of 3492 patients with gastric adenocarcinoma who underwent radical gastrectomy from 2012 to 2017 were included as the training cohort. Survival analysis was performed via Kaplan Meier method and log-rank test. Independent postoperative prognostic factors in patients with gastric adenocarcinoma were analyzed using univariate and multifactorial COX analysis methods. The prognosis nomogram was established in the training cohort and verified externally in the Surveillance, Epidemiology and End Results (SEER) database. RESULTS: According to the univariate and multifactorial COX analyses, metastatic lymph node ratio (MLNR) and five other independent prognostic factors (age at surgery, type of gastrectomy, tumor size, T stage, and pathological grade) were included in the prognostic nomogram. The nomogram had better prognostic predictive ability than the American Joint Committee on Cancer (AJCC) TNM staging in both the training (C-index: 0.736 VS. 0.668) and external validation cohort (C-index: 0.712 VS. 0.627). The calibration plots showed that the predicted survival rate was in good agreement with the actual survival rate. And the decision curve analysis (DCA) curves revealed that nomogram showed stronger ability in predicting 1-year, 3-year, and 5-year OS. CONCLUSION: This study estimated the excellent prognostic predictive power and clinical application potential of the MLNR-based nomogram, which may be used to facilitate postoperative clinical treatment decisions and potentially improve patient survival outcomes.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Nomogramas , Adenocarcinoma/cirurgia , Bases de Dados Factuais , Gastrectomia , Período Pós-Operatório , Neoplasias Gástricas/cirurgia , Prognóstico
4.
BMC Microbiol ; 23(1): 78, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949381

RESUMO

BACKGROUND: Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration of L. crispatus could prevent endometrial fibrosis and ameliorate IUA. RESULTS: First, we created a mechanically injured mouse model of IUA and restored the mice's vaginal microbiota by the addition of L. crispatus convolvulus. The observations suggested that intrauterine injections of L. crispatus significantly decreased the degree of uterine fibrosis, the levels of IL-1ß and TNF-α in blood, and downregulated the TGF-ß1/SMADs signaling pathway in IUA mice. A therapy with L. crispatus considerably raised the abundance of the helpful bacteria Lactobacillus and Oscillospira and restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect of L. crispatus with estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen. CONCLUSIONS: This study confirmed that L. crispatus could restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/ , identifier (ChiCTR1900022522), registration time: 15/04/2019.


Assuntos
Lactobacillus crispatus , Probióticos , Doenças Uterinas , Feminino , Humanos , Camundongos , Animais , Doenças Uterinas/prevenção & controle , Estrogênios , Aderências Teciduais/prevenção & controle , Modelos Animais de Doenças
5.
Molecules ; 28(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37446781

RESUMO

In this study, cathepsin D was oxidized in vitro with different concentrations of H2O2, and the activity, structure, and extent of myofibrillar protein degradation by oxidized cathepsin D were evaluated. The sulfhydryl content of cathepsin D decreased to 9.20% after oxidation, while the carbonyl content increased to 100.06%. The ß-sheet in the secondary structure altered due to oxidation as well. The changes in the intrinsic fluorescence and UV absorption spectra indicated that oxidation could cause swelling and aggregation of cathepsin D molecules. The structure of cathepsin D could change its activity, and the activity was highest under 1 mM H2O2. Cathepsin D could degrade myofibrillar proteins in different treatment groups, and the degree of degradation is various. Therefore, this study could provide a scientific basis for the mechanism of interaction among hydroxyl radical oxidation, cathepsin D, and MP degradation.


Assuntos
Catepsina D , Manipulação de Alimentos , Radical Hidroxila , Proteólise , Salmonidae , Catepsina D/química , Radical Hidroxila/química , Oxirredução , Animais , Conformação Proteica em Folha beta , Fluorescência
6.
Molecules ; 27(10)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35630714

RESUMO

Jujube cores are fiber-rich industrial waste. Dewaxing, alkali treatment, bleaching, and sulfuric acid hydrolysis were used to generate cellulose nanocrystals (CNCs) from the jujube cores in this study. The morphological, structural, crystallinity, and thermal properties of the fibers were investigated using FE-SEM, TEM, AFM, FT-IR, XRD, and TGA under various processes. CNCs' zeta (ζ) potential and water contact angle (WAC) were also investigated. The findings demonstrate that non-fibrous components were effectively removed, and the fiber particles shrunk over time because of many activities. CNCs had a rod-like shape, with a length of 205.7 ± 52.4 nm and a 20.5 aspect ratio. The crystal structure of cellulose Iß was preserved by the CNCs, and the crystallinity was 72.36%. The temperature of the fibers' thermal degradation lowered during the operations, although CNCs still had outstanding thermal stability (>200 °C). Aside from the CNCs, the aqueous suspension of CNCs was slightly agglomerated; thus, the zeta (ζ) potential of the CNCs' suspension was −23.72 ± 1.7 mV, and the powder had high hydrophilicity. This research will be valuable to individuals who want to explore the possibility for CNCs made of jujube cores.


Assuntos
Nanopartículas , Ziziphus , Celulose/química , Humanos , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química
7.
Molecules ; 24(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484430

RESUMO

The effects of chlorogenic acid (CA) (6, 30, and 150 µM/g protein) on the physicochemical and functional properties of Coregonus peled myofibrillar protein (MP) through oxidation using a hydroxyl radical oxidation system (0.01 mM FeCl3, 0.01 mM Asc, and 1 mM H2O2) were investigated. The result showed that CA inhibited the increase in protein carbonyl content but did not prevent losses in sulfhydryl and free amine contents caused by oxidation. The presence of CA also increased conformational changes in the secondary and tertiary structures of oxidized MP. Oxidized MP containing 6 µM/g CA had superior functional properties (solubility, emulsifying, foaming, and gel properties), while oxidized MP containing 150 µM/g CA aggregated, resulting in insolubility and a poor gel network.


Assuntos
Ácido Clorogênico/química , Radical Hidroxila/química , Oxirredução
8.
Food Chem X ; 21: 101063, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38162040

RESUMO

The effects of four polyphenols-chlorogenic acid (CA), gallic acid (GA), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) on the structure, gel properties, and interaction mechanisms of myofibrillar protein (MP) were studied. The changes in MP structure with polyphenols were analyzed using circular dichroism. The ultraviolet and fluorescence spectra and thermodynamic analysis indicated that the type of binding between the four polyphenols with the MP was static quenching of complex formation. GA had a more pronounced effect on improving MP gel properties. Finally, molecular docking determined that the affinity of the protein with the four polyphenols was in the order EGCG > ECG > CA > GA, with the main interaction force being hydrophobic interactions and hydrogen bonding, but hydrogen bonding dominates the interaction between GA and the protein. The findings illuminate the mechanism of MP binding to different polyphenols and facilitate the study of polyphenol-protein properties.

9.
J Infect ; 88(2): 112-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38135161

RESUMO

OBJECTIVES: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth. METHODS: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts. RESULTS: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084). CONCLUSIONS: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China.


Assuntos
Infecção Hospitalar , Estresse Financeiro , Estados Unidos , Humanos , Idoso , Estudos de Coortes , Estudos Prospectivos , Medicare , Infecção Hospitalar/epidemiologia , Hospitais , China/epidemiologia , Atenção à Saúde
10.
J Huazhong Univ Sci Technolog Med Sci ; 33(6): 862-865, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24337849

RESUMO

Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine artemesia annua L. (the blue-green herb) in the early 1970s, which has been confirmed for effectively treating malaria. Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill cancer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransferrin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling (TUNEL) and colony formation assay, respectively. The results showed that artemisinin at various concentrations significantly inhibited growth, colony formation and cell viability of SMMC-7721 cells (P<0.05), likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells (P<0.01). Our data suggest that treatment with artemisinin leads to inhibition of viability and proliferation, and apoptosis of SMMC-7721 cells. Furthermore, we observed that holotransferrin significantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Artemisininas/farmacologia , Transferrina/farmacologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Neoplasias Hepáticas/metabolismo
11.
Food Chem ; 429: 136924, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37490819

RESUMO

Ferritin has a unique hollow spherical structure, which makes it a promising nanocarrier for food functional substances. In this study, a new ferritin was successfully extracted from the liver of Northern pike, purified, and identified. We used the reversible self-assembly characteristics of ferritin to fabricate chlorogenic acid (CA)-loaded apoferritin (Apo) complex (Apo-CA) and sodium alginate (SA)-apoferritin (Apo) co-encapsulate system. Apo-CA was encapsulated into the SA system to form SA-Apo-CA. The fabricated composites were analyzed using particle size, UV-Vis absorption spectroscopy, fluorescence spectroscopy, flourier transform infrared spectroscopy and transmission electron microscope. Physicochemical property of analysis confirmed th successful preparation of Apo-CA/SA-Apo-CA and improved thermal and UV radiation stability. The effect of sustained-release of CA were tested in vitro of simulated gastrointestinal tract digestion. SA-Apo-CA exhibited greater release ability than unencapsulated CA and Apo-CA. This study provides a new strategy for designing a multilayer delivery system with improved stability and sustained-release property.


Assuntos
Ácido Clorogênico , Ferritinas , Animais , Ferritinas/química , Ácido Clorogênico/química , Preparações de Ação Retardada/química , Esocidae , Apoferritinas , Alginatos/química , Fígado
12.
Exp Ther Med ; 26(5): 506, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37822589

RESUMO

Traditional chemotherapy drugs have definite antitumor mechanisms and good therapeutic efficacy; however, their poor water solubility, serious side effects and drug resistance limit their clinical application. To the best of our knowledge, the present study reported for the first time the in vivo and in vitro anticancer effects of procyanidin B1 (PCB1), a compound that is isolated from natural sources such as grape seeds, apples, peanut skin and cranberries. Cell Counting Kit-8 assay showed that PCB1 effectively decreased the number of viable HCT-116 cells compared with cells treated with the small molecule cytotoxic drug doxorubicin. Quantitative PCR and apoptosis analysis, Cell cycle analysis, and WB analysis) of the molecular mechanism showed that PCB1 induced cell apoptosis and cell cycle arrest in S phase by increasing expression of pro-apoptosis protein caspase-3 and BAX and decreasing expression of anti-apoptosis protein Bcl-2. The efficient antitumor activity of PCB1 was demonstrated through in vivo experiments on a xenograft mouse model, demonstrating that PCB1 significantly suppressed tumor growth. The present study suggested that PCB1 represents a novel class of plant-based compounds isolated from natural sources that can be applied as an anticancer drug.

13.
Foods ; 12(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37444217

RESUMO

In this study, the quality (sensory evaluation, microbial enumerate, color, tvb-n (total volatile basic nitrogen), tca-soluble peptide (trichloroacetic acid-soluble peptide), muscle glucose, lactate, total sugar, Bas (Biogenic amines), VOCs (volatile organic compounds) and the microbial dynamic structure in samples stored at 4 °C were evaluated, and the relationship between VOCs and the diversity structure of microorganisms was also discussed. It was determined by sensory evaluation that the shelf life of samples was around 8 days. Protein and sugar were detected in large quantities by microorganisms in the later stage. At the same time, this also caused a large amount of Bas (biogenic amines) (tyramine, cadaverine, and putrescine). According to high-throughput amplicon sequencing, the initial microbiota of samples was mainly composed of Pseudomonas, Acinetobacter, Planifilum, Vagococcus, Hafnia, Mycobacterium, Thauera, and Yersinia. Among them, Pseudomonas was the most advantageous taxon of samples at the end of the shelf life. The minor fraction of the microbial consortium consisting of Vagococcus, Acinetobacter and Myroides was detected. The substances 3-methyl-1-butanol, ethyl acetate, and acetone were the main volatile components. The glucose, lactic acid, and total sugar were negatively correlated with Yersinia, Hafnia-Obesumbacterium, Thauera, Mycobacterium, and Planifilum; the proportion of these microorganisms was relatively high in the early stage. TVB-N and TCA-soluble peptides were positively correlated with Pseudomonas, Shewanella, Brochothrix, Vagococcus, Myroides, and Acinetobacter, and these microorganisms increased greatly in the later stage. The substance 3-methyl-1-butanol was positively correlated with Pseudomonas and negatively correlated with Mycobacterium. Ethyl acetate was associated with Hafnia-Obesumbacterium, Thauera, and Yersinia. Acetone was positively correlated with Acinetobacter.

14.
Foods ; 12(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37835366

RESUMO

Allicin is a kind of natural antimicrobial active substance, but its water solubility is poor, and it is easy to degrade. In order to improve the stability and bioavailability of allicin, allicin-zein composite nanoparticles (Al-Ze) were prepared by the combination method of antisolvent precipitation and electrostatic deposition, and their characteristic parameters, such as average particle size, polydispersity index (PDI), and ζ-potential, were analyzed. Then, Al-Ze was used as the delivery carrier for the active substance (allicin), and gelatin with good film-forming properties was selected as the film-forming matrix to prepare Al-Ze gelatin films. The optical properties, mechanical properties, and characterization parameters were used to analyze the prepared composite materials; the results confirmed that Al-Ze gelatin film has good mechanical properties and barrier properties. The prepared film was applied to the storage of cold, fresh beef, and the quality change of beef was monitored at 4 °C. The results showed that Al-Ze gelatin film could effectively delay the quality deterioration of beef. This paper provides a new idea and data support for the application of Al-Ze gelatin film in meat storage and fresh-keeping, and offers new insight for the promotion and application of allicin in the food industry.

15.
Foods ; 12(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36832792

RESUMO

The effects of changes in the malondialdehyde (MDA) content on the quality of fish during the low-temperature storage period are unclear. Therefore, the effects of the MDA content on Coregonus peled quality and protein changes were investigated following storage under refrigeration (4 °C) and super chilling (-3 °C) for 15 days (d). The results showed that the MDA content continued to increase during storage and that the highest content was produced at 1.42 mg/kg during refrigeration. The fillet pH, drip loss, texture (hardness and elasticity), and myofibril fragmentation index deteriorated significantly during the storage period. Increased oxidation of the myofibrillar protein (MP) was observed in the 15 d storage period, and the MP carbonyl content was 1.19 times higher under refrigeration than in super chilling, while the protein α-helix structure decreased by 12.48% and 12.20% under refrigeration and super chilling, respectively. Electropherograms also showed that myosin degradation was particularly severe in the refrigeration storage period of 15 d. Overall, the MDA formed at the refrigeration and super chilling storage temperatures could promote structural changes in, and the oxidative degradation of, proteins to different degrees, leading to the deterioration of the fillet quality. This study provides a scientific basis for investigating the relationship between fish quality and changes in the MDA content during low-temperature storage.

16.
Nutrients ; 15(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36678227

RESUMO

The current study aims to evaluate the potential roles of taking probiotics postoperatively in attenuating the gastrointestinal complications and disturbed gut microbiota in colorectal cancer (CRC) patients undergoing chemotherapy. One hundred eligible CRC patients who were treated with radical surgery and needed to receive chemotherapy were recruited. Half of them were randomly assigned to the Probio group to take a probiotic combination from post-operation to the end of the first chemotherapeutic course. The other half of patients taking placebo instead were classified as the Placebo group. Gastrointestinal complications such as nausea, acid reflux, abdominal pain, abdominal distention, constipation, and diarrhea were recorded during chemotherapy. Fecal samples were collected preoperatively and after the first cycle of postoperative chemotherapy for 16S rRNA high-throughput sequencing and short-chain fatty acids (SCFAs) analysis. Results showed that probiotics administration could effectively reduce chemotherapy-induced gastrointestinal complications, particularly in diarrhea (p < 0.01). Additionally, chemotherapy also reduced the bacterial diversity indexes of the gut microbiota in CRC patients, which could be significantly increased by taking probiotics. Moreover, this chemotherapy caused significant changes in the composition of the gut microbiota, as indicated by decreased phylum levels of Firmicutes and increased Bacteroidetes, Proteobacteria, and Verrucomicrobia. In particular, several bacterial genera such as Akkermansia and Clostridium were significantly increased, while Prevotella, Lactobacillus, and Roseburia were decreased (p < 0.05). However, probiotic administration could effectively restore these taxa changes both at the phylum and genus levels, and mildly increase the genus levels of Bifidobacterium, Streptococcus, and Blautia. Furthermore, probiotics could also promote the production of SCFAs, particularly increasing acetate, butyrate, and propionate (p < 0.0001). These results support the beneficial effects of the probiotic interventions as novel alternative or complementary strategies in chemoprevention.


Assuntos
Neoplasias Colorretais , Gastroenteropatias , Microbioma Gastrointestinal , Probióticos , Humanos , Bactérias/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Diarreia/prevenção & controle , Disbiose/microbiologia , Ácidos Graxos Voláteis/análise , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Probióticos/farmacologia , RNA Ribossômico 16S/genética
17.
Cell Rep ; 42(2): 112138, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36807141

RESUMO

The molecular mechanisms mediating the aggregation and transmission of tau in AD remain unclear. Here, we show that the actin-binding protein cofilin is cleaved by a cysteine protease asparagine endopeptidase (AEP) at N138 in the brains of patients with AD. The AEP-generated cofilin 1-138 fragment interacts with tau and promotes its aggregation. The mixed fibrils consisting of cofilin 1-138 and tau are more pathogenic to cells than pure tau fibrils. Furthermore, overexpression of cofilin 1-138 in the brain facilitates the propagation of pathological tau aggregates and promotes AD-like cognitive impairments in tau P301S mice. However, mice infected with adeno-associated viruses (AAVs) encoding an AEP-uncleavable cofilin mutant show attenuated tau pathology and cognitive impairments compared with mice injected with AAVs encoding wild-type cofilin. Together, these observations support the role of the cofilin 1-138 fragment in the aggregation and transmission of tau pathology during the onset and progression of AD.


Assuntos
Doença de Alzheimer , Animais , Humanos , Camundongos , Fatores de Despolimerização de Actina/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Cofilina 1/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Proteínas tau/metabolismo
18.
Mol Cell Biol ; 42(3): e0008921, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35191745

RESUMO

Circular RNAs (circRNAs) are implicated in diverse human cancers. However, the effects of circRNAs on cutaneous squamous cell carcinoma (CSCC) are barely known. We focused on the function of circ_0001821 in CSCC. Quantitative reverse transcription PCR was performed for the expression of circ_0001821, miR-148a-3p, and epidermal growth factor receptor (EGFR). Cell counting kit-8 assay and colony formation assay were conducted to evaluate cell viability and colony formation ability. Flow cytometry analysis was adopted to analyze cell cycle and apoptosis. A transwell assay was employed to detect cell motility. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pulldown assay were utilized to verify the interaction between miR-148a-3p and circ_0001821 or EGFR. A Western blot assay was conducted for protein levels. Murine xenograft model assay was used to explore the function of circ_0001821 in vivo. circ_0001821 level was increased in CSCC tissues and cells. circ_0001821 knockdown restrained cell viability, colony formation, cell cycle processes, and metastasis, and facilitated cell apoptosis in vitro, and restrained tumor growth in vivo. For mechanism analysis, circ_0001821 directly targeted miR-148a-3p to elevate EGFR expression. Downregulation of miR-148a-3p weakened the impacts of circ_0001821 deficiency on CSCC malignant phenotypes. Moreover, miR-148a-3p overexpression inhibited the malignant phenotypes of CSCC cells, with EGFR elevation abrogating the effects. In addition, circ_0001821 knockdown blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. circ_0001821 functioned as a tumor promoter in CSCC via regulating the miR-148a-3p/EGFR axis and PI3K/Akt pathway.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , RNA Circular , Neoplasias Cutâneas , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Receptores ErbB/genética , Humanos , Camundongos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , RNA Circular/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
19.
J Cancer ; 13(6): 1905-1913, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399728

RESUMO

Gastric cancer is one of the most severe cancers, while the relationship between Helicobacter pylori (H. pylori) and gastric cancer are still in dispute, and little work has been done to explore the microbial diversity between H. pylori positive patients and negative patients. In the present work, a total of 43 gastric cancer patients and 10 healthy 53 participants were enrolled to compare the microbial differences in community structure in gastrointestinal tract between H. pylori positive patients and negative patients with gastric cancer. Our results indicated that the abundance and diversity of gastrointestinal microbiota was slight lower in gastric cancer patients than that in healthy participants especially in intestine, while the abundance of some potential pathogens, e.g. Streptococcus, Lactobacillus, Akkermansia and Halomones were higher in H. pylori positive patients than H. pylori negative patients. Therefore, our work suggests the various microbial diversity between H. pylori positive patients and H. pylori negative patients with gastric cancer, which contribute to deepen the understanding of the role of H. pylori in gastric carcinogenesis and progression.

20.
J Food Sci ; 87(7): 2932-2942, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35638344

RESUMO

Tenderness affects mutton quality and price, and the degradation of myofibrillar protein (MP) is critical to improve tenderness. We investigated the oxidative modification of mutton MP by hydroxyl radicals (OH) and the effects of this modification on the proteolysis of MP by µ-calpain. As the H2 O2 concentrations increased, the carbonyl and dityrosine contents and the surface hydrophobicity of MP all display an increasing trend, whereas the total sulfhydryl and intrinsic fluorescence intensity of MP declines significantly. SDS-PAGE electrophoresis indicates that disulfide bonds and other covalent bonds led to protein cross-linking and aggregation. After adding µ-calpain, with increasing oxidation, the degradation percentage of myosin heavy chain (MHC) increases considerably and actin degradation is promoted, while the proteolysis of troponin-T and desmin is inhibited. These data suggest that·OH can change MP physicochemical properties and its susceptibility to µ-calpain. Future investigations will focus on the effect of oxidation on the degradation of MP by other proteases, such as cathepsins and caspase and the effect of oxidation on these enzymes. PRACTICAL APPLICATION: The calpain system, particularly µ-calpain, plays a pivotal role in postmortem tenderization of meat. Protein oxidative modifications influence meat tenderness mainly by regulating proteolysis. An investigation of the effect of oxidation on the proteolytic susceptibility of MP to degradation by µ-calpain allows for the monitoring of the association between protein oxidation and meat tenderness.


Assuntos
Calpaína , Carne Vermelha , Calpaína/química , Carne/análise , Músculo Esquelético/química , Miofibrilas/química , Oxirredução , Proteólise , Carne Vermelha/análise
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