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1.
Int J Oral Sci ; 13(1): 31, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593756

RESUMO

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.


Assuntos
Colite Ulcerativa , Porphyromonas gingivalis , Desiminases de Arginina em Proteínas , Animais , Colite Ulcerativa/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/patogenicidade , Fatores de Virulência
2.
Food Chem ; 372: 131266, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34628117

RESUMO

The food-derived peptides hydrolyzed from native food protein matrix exhibited various bioactivities and multimeric structures, which make them the promising well-defined nanoplatforms candidates to co-deliver themselves with other bioactive compounds. In this study, zein-egg white derived peptides-chitosan (Z-EWDP-CS) ternary nanoparticles (NPs) were successfully fabricated by the spontaneous assembly to enhance the stability and bioactivity of curcumin (Cur). The novel ternary NPs exhibited a typical nano-spherical structure (138.63 nm, 40.50 mV), and adorable encapsulation efficiency (EE, 93.87%) for Cur. FTIR, XRD and DSC results verified that Cur changed from a crystalline state to an amorphous state, and was successfully entrapped in the cavity of Z-EWDP-CS NPs. Furthermore, the thermal stability, photochemical stability, salt stability, and antioxidant activity were considerably improved in the NPs after the addition of EWDP. Our results demonstrate that the food-derived peptides could be an ideal affinity agent for the co-delivery of themselves with hydrophobic nutraceuticals.

3.
Biochem Biophys Res Commun ; 577: 95-102, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34509725

RESUMO

OBJECTIVE: Long non-coding RNAs (lncRNAs) are implicated in cancer-related cellular behaviors. Our research aimed to explore the biological functions of lncRNA AL592284.1 (AL592284.1) in cervical cancer (CC). METHODS: qRT-PCR was performed to examine AL592284.1 expressions in cell lines and tumor specimens. To study the roles of AL592284.1 on malignant behaviors in both in vitro and in vivo, Loss-of-function assays were carried out. Besides, bioinformatics prediction and dual-luciferase reporter assays were performed to reveal the interaction among AL592284.1 and its target genes. The functions of the AL592284.1/miR-30a-5p/Vimentin axis in CC cells was clarified by rescue assays. RESULTS: We observed that the levels of AL592284.1 in CC were distinctly increased. Functional assays revealed that knockdown of AL592284.1 suppressed the proliferation, migration, invasion and EMT progress of CC cells. Luciferase reporter assay confirmed that miR-30a-5p/Vimentin regulatory axis is the direct downstream of AL592284.1. Rescue experiments indicated that AL592284.1 induced overexpression of Vimentin via sponging miR-30a-5p, resulting in the promotion of CC progression. CONCLUSION: The present study proves that AL592284.1 plays an tumor-promotive role in CC via regulating the miR-30a-5p/Vimentin axis, and inhibition of AL592284.1 may pave the way for CC treatment.

4.
Mol Oncol ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482626

RESUMO

Sonic hedgehog (Shh)-driven medulloblastoma (Shh MB) cells are dependent on constitutive Shh signaling, but targeted treatment of Shh MB has been ineffective due to drug resistance. The purpose of this study was to address the critical role of signal transducer and activator of transcription 3 (STAT3) in Shh signaling and drug resistance in Shh MB cells. Herein, we show that STAT3 is required for Smoothened (Smo)-dependent Shh signaling and, in turn, is reciprocally regulated by Shh signaling, and demonstrate that STAT3 activity is critical for expression of HCK proto-oncogene, Src family tyrosine kinase (Hck) in Shh MB. We also demonstrate that maintained STAT3 activity suppresses p21 expression and promotes colony formation of Shh MB cells, whereas dual treatment with inhibitors of both Smo and STAT3 results in marked synergistic killing and overcomes drug resistance in vitro of Smo antagonist-resistant Shh MB cells. Finally, STAT3 inhibitor treatment significantly prevents in vivo tumor formation in genetically engineered Shh MB mice. Collectively, we show that STAT3 is necessary to maintain Shh signaling and thus is a potential therapeutic target to treat Shh MB and overcome anti-Smo drug resistance.

5.
Food Funct ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34568882

RESUMO

Egg white derived peptides (EWDP) and curcumin are well known for diverse biological activities, but the combinational usage of the two natural nutraceuticals is extremely limited by their low oral bioavailability and distinctly different polarities. Therefore, this study aimed to exploit a facile self-assembled amphiphilic system for oral co-delivery of hydrophilic egg white derived peptides (EWDP) and hydrophobic curcumin. The hydrophobic curcumin was first loaded into the hydrophobic cavity of ß-cyclodextrin (ß-CD) as a core. Then, the hydrophilic EWDP was absorbed into the region between the core and the N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan (HTCC) shell to form the amphiphilic nanoparticles (NPs) via layer-by-layer self-assembly. The resulting NPs showed ideal oral applicability with excellent colloidal properties and encapsulation capacity for EWDP and curcumin at pH 2.0-7.0. X-ray Photoelectron Spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results indicated that hydrogen bonding and hydrophobic interaction were the main driving force for the formation of amphiphilic NPs. Upon combination with HTCC, EWDP (both shell material and core nutraceuticals) could facilitate curcumin loading into the deeper ß-CD cavity site with admirable solubility improvement. Moreover, EWDP and curcumin after co-delivery exhibited superior bioavailability (especially for bioactivity and cellular absorption) than the simple mixture and conventional curcumin inclusion complex. Overall, these findings are enlightening for the rational peptide based oral co-delivery system formulations for a broader range of hydrophilic and hydrophobic nutraceuticals (initially synergistic or not) in the food and related health-promoting fields.

6.
Sci Total Environ ; 805: 150368, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34543792

RESUMO

Glyphosate (GLY), a ubiquitous environmental pollutant, can result in gut microbiota dysbiosis intimately involving various diseases. The latest research has shown an association between gut microbiota alteration and defective spermatogenesis. Here, we aimed to investigate whether GLY-induced gut microbiota dysbiosis contributed to male reproductive toxicity. Data showed that GLY-exposed rats exhibited male reproductive dysfunction, evidenced by impaired testis architectural structure, reduced sperm motility, together with increased sperm malformation ratio. 16S rDNA sequencing analysis indicated that GLY exposure altered the composition of gut commensal microbiota, of which the relative abundance of Bacteroidetes and Firmicutes phyla was significantly changed. Unexpectedly, the increased abundance of Prevotella_1 and Bacteroides genera was negatively correlated with sperm quality. Mechanistically, the pathological changes in GLY-exposed testis were accompanied by the increased interleukin (IL)-17A production, probably due to gut microbes-derived Th17 cell migration. Furthermore, activation of IL-17A signaling triggered testicular oxidative damage. Taken together, these findings uncover an underlying mechanistic scenario that gut microbiota dysbiosis-driven local IL-17A production is one reason responsible for male reproductive toxicity induced by GLY, which provides new insights into the male reproductive toxicity of GLY in mammals.

7.
Poult Sci ; 100(11): 101410, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587537

RESUMO

This study was conducted to determine the effect of 25-hydroxyvitamin D (HDV) and essential oils (EO) on the uterus antioxidant capacity, egg quality, and eggshell ultrastructure in laying hens. A total of 400 48-wk-old Lohmann laying hens were randomly allocated into 2 groups and fed a basal diet (control) or a basal diet supplemented with a combination of 69 µg/kg HDV and EO (including 200 mg/kg thymol and 50 mg/kg carvacrol) for 12 wk. There are 10 replicates of 20 hens each. Compared with the control, dietary HDV+EO supplementation improved (P < 0.05) egg production rate, feed efficiency, eggshell thickness and strength, and decreased (P < 0.05) the translucent egg score. Ultrastructural changes indicated that dietary HDV+EO supplementation decreased (P < 0.05) mammillary knob width, mammillary thickness and the proportion of mammillary thickness, and increased (P < 0.05) the proportion of effective thickness and total thickness of the eggshells compared with the control. Supplementation with HDV+EO complex led to higher serum HDV concentration and increased antioxidant capacity in the uterus, indicated by higher (P < 0.05) antioxidant enzyme activities (catalase [CAT], total antioxidant capacity [T-AOC], and glutathione S-transferases [GST]) and lower malondialdehyde (MDA) content. Therefore, dietary HDV and EO complex (including thymol and carvacrol) supplementation can improve the productive performance and the eggshell quality in laying hens, and the improving effect on eggshell quality may through enhancing eggshell ultrastructure and antioxidant capacity of uterus.

8.
Poult Sci ; 100(11): 101429, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34555757

RESUMO

The objective of this experiment was to investigate the influence of dietary tributyrin on reproduction performance and ovary function of broiler breeders with different egg laying rate. Two hundred fifty-six AA broiler breeders (48-wk-old) were allocated to 4 treatment in a 2 × 2 factorial arrangement with the main effects of tributyrin supplementation (0 and 1,000 mg/kg tributyrin [TRI]) and 2 egg laying rate levels (average [AR, 81.01 ± 0.79%] and low [LR, 70.98 ± 0.95%]). The results shown that the LR breeders presented higher egg weight, but lower egg laying rate, qualified egg rate and feed efficiency than the AR breeders (P(laying) < 0.05). Also, the superoxidase dismutase (SOD) activity in magnum was lower while malondialdehyde (MDA) was higher in ovary and magnum of LR breeders than that in the AR breeders (P(laying) < 0.05). Dietary supplementation with tributyrin significantly enhanced egg weight (P(TRI) < 0.05), increased albumen height as well as Haugh unit (HU) in AR breeders (P(interaction) < 0.05), and also had higher total antioxidant capacity (T-AOC) and lower MDA in ovary (P(TRI) < 0.05). The cell apoptosis rate and proapoptosis related gene expression (caspase 8, 9 and Bax) in the ovary of LR breeders was higher, while anti-apoptosis related gene (Bcl-2) expression were lower in LR breeders when compared with the AR breeders (P(laying) < 0.05). Dietary supplementation with tributyrin decreased the cell apoptosis rate and downregulated caspase 9 expression in LR breeders (P(Interaction) < 0.05), up-regulated the Bcl-2 expression in both 2 breeders (P(TRI) < 0.05). These findings suggest that the breeders with lower egg laying rate also characterized by deteriorate ovary function indicated by lower antioxidant capacity and higher cell apoptosis rate. Dietary supplementation with tributyrin increased egg albumen quality, decreased ovarian proapoptosis related gene expression to improve reproductive tract function; and the positive effect on egg albumen quality is more pronounced in average reproductive breeders.

9.
J Periodontal Res ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34514591

RESUMO

OBJECTIVE: To evaluate the influence of diverse anti-rheumatic agents on the periodontal condition and to provide clinical medication guidance for patients with rheumatoid arthritis (RA) and periodontitis. BACKGROUND: In recent years, the correlation between RA and periodontitis has become a hot research topic, but no medication recommendations for patients with RA and periodontitis are available at present. METHODS: The protocol of this review was registered in advance with PROSPERO (CRD42021248827). Electronic search and manual searches up to March 20, 2021 were conducted. The inclusion criteria for the studies were as follows: included patients diagnosed with periodontitis and RA submitted to anti-rheumatic agent therapy; with a control group receiving no anti-rheumatic agent therapy; with outcomes including at least one periodontal parameter. Probing depth (PD) and clinical attachment loss (CAL) were pooled using weighted mean difference (WMD) and 95% confidence intervals (CI) while gingival index (GI)/modified gingival index (MGI) was analyzed by standardized mean difference (SMD) and 95% CI. RESULTS: One thousand four hundred and seventy-eight studies potentially related to the aim of this review were screened, but only 463 patients from 14 studies were included in the qualitative analysis, and 146 patients from 4 studies were included in the meta-analysis. Statistically significant reductions were observed among the subjects who received anti-rheumatic agents for PD [WMD = -0.20; 95% CI (-0.33, -0.07); effect p = .003; I2  = 50%; p = .11], CAL [WMD = -0.4; 95% CI (-0.66, -0.15); effect p = .002; I2  = 57%; p = .07] and GI/MGI [SMD = -0.61;95% CI (-0.94, -0.27; effect p = .0004; I2  = 26%; p = .25]. Consistent with the above results, this systematic review produced promising results that PD, CAL, GI/MGI, and bleeding on probing (BOP) decreased when patients with RA and periodontitis were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), anti-B lymphocyte agents, anti-IL-6R agents, or JAK inhibitors. PD and CAL declined after the administration of anti-TNF-α agents; most studies reported decreased GI/MGI and BOP, while 2 studies reported increased GI/MGI and BOP. CONCLUSIONS: These results revealed that csDMARDs, anti-B lymphocyte agents, anti-IL-6R agents, anti-TNF-α agents, and JAK inhibitors had potential positive effects in improving the periodontal condition of patients with RA and periodontitis. However, future research is needed to elucidate whether anti-TNF-α agents have a side effect of increased gingival inflammation.

10.
Food Chem ; 368: 130839, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34419799

RESUMO

Human bitter taste receptor TAS2R14 (T2R14) can widely perceive bitterness, which has always been an issue for people to overcome. This study was aimed at identifying bioactive peptides obtained from Oncorhynchus mykiss nebulin hydrolysates as bitter taste receptor blockers by physicochemical property prediction, molecular docking, and in vitro determination of bitterness intensity using electronic tongue. Exploration of the interaction mechanism of these peptides with T2R14 by molecular docking models indicated that peptides ADM and ADW had high affinities for T2R14 to block the binding of bitter substances into the receptor. Addition of ADM and ADW to quinine caused reduction in bitterness intensity, with IC50 values of 420.32 ± 6.26 µM and 403.29 ± 4.10 µM, respectively. Hydrogen bond interaction and hydrophobic interaction were responsible for manifesting the high affinities of these peptides for the receptor. Residues Thr86, Asp168, and Phe247 may be the key amino acids within the binding site.

11.
J Agric Food Chem ; 69(35): 10350-10357, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34448567

RESUMO

As a membrane protein, the activity of angiotensin I-converting enzyme (ACE) can be modulated via regulation of its localization in the cell membrane with food-derived peptides. This study aimed to explore the effect of egg white peptides on the cell membrane localization and activity of ACE in human umbilical vein endothelial cells. ACE activity was found to be related to lipid rafts by using methyl-ß-cyclodextrin (MßCD). QVPLW and LCAY can inhibit ACE activity by preventing ACE recruitment into lipid rafts, with in situ IC50 values of 238.46 ± 11.35 µM and 31.55 ± 2.64 µM in the control groups, as well as 45.43 ± 6.15 µM and 34.63 ± 1.59 µM in the MßCD groups, respectively. QVPLW and LCAY may alter the cell membrane properties, including the fluidity, potential, and permeability, and eventually promote the transposition of ACE.


Assuntos
Clara de Ovo , Peptidil Dipeptidase A , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Microdomínios da Membrana , Peptídeos/farmacologia
12.
Exp Hematol ; 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34464661

RESUMO

Hematopoietic stem cells (HSCs) are immature blood cells that exhibit multilineage differentiation capacity. Homeostasis is critical for HSC potential and lifelong hematopoiesis, and HSC homeostasis is tightly governed by both intrinsic molecular networks and microenvironmental signals. The evolutionarily conserved serine/threonine protein kinase B (PKB, also referred to as Akt)-mammalian target of rapamycin (mTOR) pathway is universal to nearly all multicellular organisms and plays an integral role in most cellular processes. Emerging evidence has revealed a central role of the Akt-mTOR network in HSC homeostasis, because it responds to multiple intracellular and extracellular signals and regulates various downstream targets, eventually affecting several cellular processes, including the cell cycle, mitochondrial metabolism, and protein synthesis. Dysregulated Akt-mTOR signaling greatly affects HSC self-renewal, maintenance, differentiation, survival, autophagy, and aging, as well as transformation of HSCs to leukemia stem cells. Here, we review recent works and provide an advanced understanding of how the Akt-mTOR network regulates HSC homeostasis, thus offering insights into future clinical applications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34309423

RESUMO

Dental stem cells (DSCs) are mesenchymal stem-cell-like populations with self-renewal and multidifferentiation potential. These cells have been studied in regenerative medicine and tissue engineering. Despite rapid progress in the past two decades, there has been no bibliometric analysis of DSC research. Here, we performed a comparative study using bibliometric methods for DSCs. A total of 5498 articles were included. Our results showed that the United States was the leader in international cooperation and numbers of citations, and was the largest contributor. The Journal of Endodontics published the largest number of papers. The author with the greatest contribution was Shi Songtao. The keywords were mainly related to the fields of tissue engineering and regenerative medicine. Relative research interest and the number of publications increased yearly worldwide. The hotspots of DSC research were transiting from basic research to clinical regenerative medicine.

14.
Food Funct ; 12(17): 7688-7698, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34282438

RESUMO

Recent studies have indicated that active peptides can induce an improvement in wound repair. Herein, we evaluated egg white peptides (EWPs) as a nutritional supplement to improve mechanical skin damage in BALB/c mice. Two symmetrical circular full-thickness wounds were created with 5 mm biopsy punches in the skin of the mouse dorsal region, and EWPs (200, and 400 mg kg-1) were administrated by gavage for 14 days. We analyzed the EWPs for their in vivo and in vitro antioxidant capability, toxicity, and microscopy of skin wounds, and there was no cytotoxicity or in vivo toxicity. During the period of wound healing, EWPs could promote healthy cell migration, increase serum superoxide dismutase and catalase activities and accelerate the wound healing process in a time- and dose-dependent manner, whereas the levels of malondialdehyde and reactive oxygen species showed the opposite trend. After administration with 400 mg kg-1 EWPs for 10 days, the wound had almost healed. Meanwhile, EWPs significantly enhanced serum amino acids, particularly enhancing the content of Arg, Glu, Pro, Met, and Lys, which could provide sufficient nutrition in the wound healing process. The present study demonstrates that EWPs possess a positive potential to accelerate the wound healing process of mechanical skin damage at the cellular and animal level.

15.
Chemosphere ; 280: 130823, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34162096

RESUMO

Glyphosate (GLY) frequently detected in various water bodies has imposed a serious risk on fish. Head kidney of fish is an important defense organ, playing a vital part in antagonizing exogenous hazardous matter. The objective of this study was to characterize toxic mechanisms of GLY in head kidney of common carp based on transcriptome profiling. After 45-days exposure of GLY at environmentally relevant concentrations, juvenile common carp were used as experimental subjects to analyze how the head kidney responded to GLY. The transcriptome profiling identified 1381 different expressed genes (DEGs) between the control and exposure groups (5 and 50 mg/L). Functional analysis of DEGs substantiated over-representative pathways mainly involving cellular stress responses, cell proliferation and turnover, apoptosis, lipid metabolism, and innate immune processes in both treated groups compared with the control group. Predicted network of gene regulation indicated that GLY-induced tp53 played a vital role in linking a battery of signals. Furthermore, the expression of 10 candidate genes by qRT-PCR aligned with transcriptional profiling. In addition, western blotting analysis confirmed that GLY-induced apoptosis and cellular proliferation were closely involved in activating MAKP signaling pathway and lipid metabolism pathway in both treated groups. Collectively, these data demonstrate that head kidney of juvenile common carp mainly leverages upregulation of genes related to cell proliferation and turnover, apoptosis, and lipid metabolism to combat sub-chronic exposure of GLY. This study casts new understanding into the risk of GLY in aquatic animals.


Assuntos
Carpas , Animais , Carpas/genética , Perfilação da Expressão Gênica , Glicina/análogos & derivados , Glicina/toxicidade , Rim Cefálico , Transcriptoma
16.
Food Chem Toxicol ; 154: 112353, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34146619

RESUMO

This study aimed was to explore the hepatoprotective potential of soybean meal peptides (SPs) against alcohol-induced liver injury and investigate the underlying mechanisms through transcriptome analysis. The chemical antioxidant analysis of SPs exhibited potent ABTS radical scavenging capacity (11.94 ± 0.41 mg TE/100 mg peptide), ferric reducing antioxidant power (6.42 ± 0.32 mmol Fe2+/100 mg peptide), and oxygen radical absorption capacity (14.78 ± 0.01 mg TE/100 mg peptide). Moreover, SPs increased cell viability and reduced intracellular reactive oxygen species levels in Caco-2 cells by H2O2-induced, and without cytotoxicity. In the mice model, preintervention with SPs reduced the levels of aspartate transaminase/alanine transaminase, total cholesterol, triglyceride and malondialdehyde by alcohol-induced, meanwhile, increased the levels of total superoxide dismutase, glutathione and catalase by alcohol-induced. Histological analysis showed that SPs alleviated the liver injury by alcohol-induced and no toxic effects on the kidneys. According to transcriptome analysis, 1737 genes were significantly differentially expressed (1076 up-regulated and 661 down-regulated) after SPs pretreatment. The main functions of these genes were related to inflammation, lipid metabolism and oxidation. The findings from the present study suggested that SPs produced positive hepatoprotection and showed potential to be used as a dietary supplement or an ingredient of functional food.

17.
Food Funct ; 12(13): 5989-6000, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34037039

RESUMO

Food-derived peptides can ameliorate colitis but their pharmaceutical targets and action mechanism of ameliorating colitis remain unclear. Here, we aim to investigate the action mechanism of food-derived peptides ameliorating colitis based on the network pharmacology and bioinformatics analysis. 400 dipeptides were used to screen the core targets based on the PharmMapper and GeneCards database. A total of 49 core targets were screened to construct the predicted target set. The target set was then evaluated using the STRING software to construct the protein-protein and protein-dipeptide network. Furthermore, the DAVID software was used to analyze the GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of the core targets. The results of bioinformatics assays showed that the 49 targets mainly participated in the inflammatory and immunomodulatory signaling pathways, particularly in the inflammatory bowel disease-related signaling pathways IL-6/JAK2/STAT3 and TLR4-NF-κB/MAPK. In addition, molecular docking results confirmed that 25 dipeptides mainly interacted with the core targets (ALB, JAK2, and STAT3) by hydrogen-bonding interactions. This study can provide evidence for the potential efficacy and action pathways of food-derived peptides on colitis.

18.
Sci Adv ; 7(18)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33931452

RESUMO

RNA-based therapies offer unique advantages for treating brain tumors. However, tumor penetrance and uptake are hampered by RNA therapeutic size, charge, and need to be "packaged" in large carriers to improve bioavailability. Here, we have examined delivery of siRNA, packaged in 50-nm cationic lipid-polymer hybrid nanoparticles (LPHs:siRNA), combined with microbubble-enhanced focused ultrasound (MB-FUS) in pediatric and adult preclinical brain tumor models. Using single-cell image analysis, we show that MB-FUS in combination with LPHs:siRNA leads to more than 10-fold improvement in siRNA delivery into brain tumor microenvironments of the two models. MB-FUS delivery of Smoothened (SMO) targeting siRNAs reduces SMO protein production and markedly increases tumor cell death in the SMO-activated medulloblastoma model. Moreover, our analysis reveals that MB-FUS and nanoparticle properties can be optimized to maximize delivery in the brain tumor microenvironment, thereby serving as a platform for developing next-generation tunable delivery systems for RNA-based therapy in brain tumors.

19.
Food Chem ; 360: 129981, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34020366

RESUMO

Egg white peptides (EWPs) can be effectively used to alleviate and treat inflammatory diseases due to their anti-oxidation, anti-inflammation, and microbiota regulation capabilities. A dextran sodium sulfate (DSS)-induced colitis model was used to clarify the regulatory effects of EWPs on colitis. Forty-three peptide sequences were identified from EWPs using LC-MS/MS. The results demonstrated that EWPs decreased the levels of pro-inflammatory cytokines and the extent of crypt damage in a dose-dependent manner. 16S rRNA gene sequencing results indicated that 200 mg/kg EWPs significantly increased the relative abundance of beneficial bacteria Lactobacillus and Candidatus_Saccharimonas, and reduced the relative abundance of pathogenic bacteria Ruminiclostridium and Akkermansia. In addition, the degree of correlation between pro-inflammatory cytokines and microbiota was as follows: interleukin (IL)-1ß > IL-8 > IL-6 > tumor necrosis factor-α To summarize, EWPs contributed to the alleviation of colitis symptoms and the intestinal injury through anti-inflammatory effects, repair of intestinal mucosa, and modulation of gut microbiota.


Assuntos
Colo/metabolismo , Citocinas/metabolismo , Clara de Ovo/química , Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Sulfato de Dextrana/toxicidade , Proteínas do Ovo/química , Proteínas do Ovo/metabolismo , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/análise , Peptídeos/uso terapêutico , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/metabolismo , Espectrometria de Massas em Tandem
20.
Cancers (Basel) ; 13(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799550

RESUMO

Sonic hedgehog subtype of medulloblastoma (SHH MB) with metastasis or specific clinical or molecular alteration shas a poor prognosis and current therapy results in long-term cognitive impairment in the majority of survivors. Thus, a great need exists for new targeted therapeutic approaches to more effectively treat SHH MB in children. Imipramine blue (IB), a novel molecule with anti-tumor properties, inhibits the NADPH oxidase (NOX) family of enzymes, which are critical for SHH MB survival and treatment resistance. In this study, IB was encapsulated within a liposome to form a liposomal nanoparticle, Liposome-IB (Lipo-IB). This complex has the ability to cross the blood-brain barrier and be preferentially taken up by tumor cells within the brain. We demonstrated in vitro that Lipo-IB treatment caused a dose-dependent decrease in SHH MB cell viability and migration. Short-term administration of single agent Lipo-IB treatment of SHH MB in vivo significantly inhibited tumor growth, reduced the tumor volume, including a complete tumor response, and improved survival compared to control treated mice, without any observable toxicity. We conclude that Lipo-IB is a potential novel nanoparticle-based therapeutic for the treatment of SHH MB that warrants further preclinical safety and efficacy testing for development towards clinical investigation.

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