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1.
Molecules ; 28(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37049676

RESUMO

Polysaccharides with molecular weights ranging from 1.75 × 103 to 1.14 × 104 g/mol were obtained from the fruit bodies of Ganoderma lucidum. The multiple fingerprints and macrophage immunostimulatory activity of these fractions were analyzed as well as the fingerprint-activity relationship. The correlation analysis of molecular weight and immune activity demonstrated that polysaccharides with molecular weights of 4.27 × 103~5.27 × 103 and 1 × 104~1.14 × 104 g/mol were the main active fractions. Moreover, the results showed that galactose, mannose, and glucuronic acid were positively related to immunostimulatory activity. Additionally, partial least-squares regression and grey correlation degree analyses indicated that three peaks (P2, P3, P8) in the oligosaccharide fragment fingerprint significantly affected the immune activity of the polysaccharides. Hence, these ingredients associated with activity could be considered as markers to assess Ganoderma lucidum polysaccharides and their related products, and the study also provides a reference for research on the spectrum-effect relationship of polysaccharides in the future.


Assuntos
Ganoderma , Reishi , Quimiometria , Polissacarídeos/farmacologia , Polissacarídeos/análise , Macrófagos , Imunomodulação
2.
J Sci Food Agric ; 101(13): 5618-5626, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33709431

RESUMO

BACKGROUND: Metabolite formation is a physiological stress response during the growth and development of shiitake mushrooms (Lentinula edodes). The characteristic flavor metabolites are important quality components in shiitake mushrooms. To investigate the formation mechanisms of characteristic flavor metabolites, transcriptome analyses were performed on shiitake mushrooms harvested at different growth stages. RESULTS: In total, 30 genes related to the synthesis of characteristic volatiles of mushrooms were identified via screening. Through KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis of the selected genes and correlation analyses of gene expressions, the main volatile synthesis pathways were determined as histidine metabolism, glutathione metabolism and biosynthesis of unsaturated fatty acids. Gene cluster and correlation analyses were performed to clarify the combined effects of different genes in the enzymatic reactions. Further, a correlation network of candidate genes was built based on the gene expression levels. CONCLUSION: The activities of flavor synthases and the content of characteristic flavor metabolites were analyzed; the enzyme activity changes and metabolic product distribution sites were clarified. A synthesis and regulation network was constructed for the candidate genes and characteristic volatiles, and information was obtained for 16 hub genes. Moreover, it was essential to identify and characterize the key genes and synthases involved in the synthesis of the characteristic volatiles of mushrooms. This information provides us with a better understanding of the biosynthesis and regulation of the volatiles, which will lay the foundation for improving the quality of shiitake mushrooms. © 2021 Society of Chemical Industry.


Assuntos
Aromatizantes/metabolismo , Proteínas Fúngicas/genética , Cogumelos Shiitake/genética , Vias Biossintéticas , Aromatizantes/química , Proteínas Fúngicas/metabolismo , Redes Reguladoras de Genes , Odorantes/análise , Cogumelos Shiitake/química , Cogumelos Shiitake/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo
3.
Molecules ; 25(16)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823661

RESUMO

Sanghuangporous sanghuang is a rare medicinal fungus which contains polysaccharide as the main active substance and was used to treat gynecological diseases in ancient China. The intracellular polysaccharide yield of S. sanghuang was enhanced by the strain A130 which was screened from mutant strains via atmospheric and room temperature plasma (ARTP) mutagenesis. The objective of this research was to investigate the effects of ARTP mutagenesis on structural characteristics and biological activities of intracellular polysaccharides from S. sanghuang. Six intracellular polysaccharide components were obtained from S. sanghuang mycelia cultivated by the mutagenic strain (A130) and original strain (SH1), respectively. The results revealed that the yields of polysaccharide fractions A130-20, A130-50 and A130-70 isolated from the mutagenic strain fermentation mycelia were significantly higher than those of the original ones by 1.5-, 1.3- and 1.2-fold, and the clear physicochemical differences were found in polysaccharide fractions precipitated by 20% ethanol. A130-20 showed a relatively expanded branching chain with higher molecular weight and better in vitro macrophage activation activities and the IL-6, IL-1, and TNF-α production activities of macrophages were improved by stimulation of A130-20 from the mutagenic strain. This study demonstrates that ARTP is a novel and powerful tool to breed a high polysaccharide yield strain of S. sanghuang and may, therefore, contribute to the large-scale utilization of rare medicinal fungi.


Assuntos
Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Espaço Intracelular/metabolismo , Mutagênese , Polyporales/citologia , Animais , Polissacarídeos Fúngicos/biossíntese , Fatores Imunológicos/biossíntese , Camundongos , Polyporales/genética , Células RAW 264.7
4.
Anal Biochem ; 579: 38-43, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31125532

RESUMO

The quantitative determination of small molecules by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI TOF MS) was always challenging, due to low sensitivity and interferences of matrix and other contaminants on sample plates. Here we report a disposable paper-array (PA) plate in MALDI TOF MS analysis for quantitative analysis of serum free fatty acids (FFAs) with less interference and higher sensitivity, compared with conventional stainless steel (SS) plate. The disposable PA plate was low cost and environmentally friendly. In particular, it was more sensitive in FFAs detection with ~8-34-fold sensitivity increase for eight FFAs as compared to SS plate. Eight serum FFAs in gout patients were investigated using this disposable PA plate. The quantitative results showed good linearity of all eight FFAs between 0.1 and 2.5 mM with correlation coefficients between 0.994 and 0.999 and limits of detection (LODs) between 8.6 and 104.2 µM. Mann-Whitney U test, principal component analysis (PCA) and random forest categorizer allowed the clear separation of gout patients from healthy controls, according to eight FFAs levels in serum detected by disposable PA plate based MALDI TOF MS.


Assuntos
Biomarcadores/sangue , Ácidos Graxos não Esterificados/sangue , Gota/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Equipamentos Descartáveis , Humanos
5.
Carbohydr Polym ; 332: 121916, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431417

RESUMO

Resveratrol (RES) is a natural polyphenol with excellent biological activity. But the poor stability and bioavailability of RES severely limit its application. Thus, the resveratrol-loaded sulfated Hericium erinaceus ß-glucan-chitosan nanoparticles (DS-CS-RES NPs) were prepared using electrostatic self-assembly to solve these problems in this study. The structure of DS-CS-RES NPs was spherical or sub spherical shape with small average particle size (191.07 nm), which was characterized by FT-IR, FS, XRD and TEM. DS-CS-RES NPs exhibited good stability and RES had a sustainable release from the nanoparticles in gastrointestinal digestion. Meanwhile, DS-CS-RES NPs could improve the inflammatory injury of LPS stimulated RAW264.7 macrophages by inhibiting the production of NO, IL-1ß, IL-6 and TNF-α. Furthermore, DS-CS-RES NPs had strong anti-inflammatory activity by regulating protein levels of NF-κB p65, STAT1 and TLR4 through NF-κB and JAK-STAT1 signaling pathway in vitro, and sulfated H. erinaceus ß-glucan-chitosan nanoparticle (DS-CS NPs) and RES had synergistic anti-inflammatory effect. Overall, DS-CS NPs can serve as a potential green and safe functional carrier for encapsulating resveratrol, which can improve its anti-inflammatory activity. This work may be conducive to the development of functional carrier for encapsulating RES and applications of hydrophobic active molecules in functional foods or medicines.


Assuntos
Quitosana , Hericium , Nanopartículas , Resveratrol/farmacologia , Quitosana/química , Portadores de Fármacos/química , NF-kappa B , Sulfatos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Tamanho da Partícula
6.
Food Chem ; 439: 138138, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38134569

RESUMO

Umami peptides enhance flavor and offer potential health benefits. We analyzed the taste-value profiles of five novel umami peptides from Stropharia rugosoannulata using E-tongue, exhibiting significant saltiness characteristics. While the peptides PHEMQ and SEPSHF exhibited higher saltiness, their mixture with salt did not enhance saltiness compared to individual peptides. Surprisingly, SGCVNEL, which was initially weak in saltiness, showed remarkably enhanced saltiness when mixed with salt, possibly due to have strong binding with receptors. Molecular docking elucidated the salt-forming mechanism of TMC4, highlighting the P2-domain and hydrogen bonds' role in the composite structure stability. Evaluation of the antioxidant activity evaluation demonstrated dose-dependent effects primarily through free radical scavenging via the single-electron transfer potential mechanism for SGCVNEL, EPLCNQ, and ESCAPQL. Docking experiments with antioxidant targets revealed varied binding stabilities, indicating diverse antioxidant effects of the peptides. These findings provide valuable insights into the exploration and application of versatile bioactive flavor peptides.


Assuntos
Antioxidantes , Paladar , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Peptídeos/química , Cloreto de Sódio na Dieta , Cloreto de Sódio/farmacologia
7.
Curr Cancer Drug Targets ; 24(6): 642-653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38310462

RESUMO

BACKGROUND: Immune-checkpoint inhibitors (ICIs) against programmed death (PD)-1/PD-L1 pathway immunotherapy have been demonstrated to be effective in only a subset of patients with cancer, while the rest may exhibit low response or may develop drug resistance after initially responding. Previous studies have indicated that extensive collagen-rich stroma secreted by cancer-associated fibroblasts (CAFs) within the tumor microenvironment is one of the key obstructions of the immunotherapy for some tumors by decreasing the infiltrating cytotoxic T cells. However, there is still a lack of effective therapeutic strategies to control the extracellular matrix by targeting CAFs. METHODS: The enhanced uptake of IR-780 by CAFs was assessed by using in vivo or ex vivo nearinfrared fluorescence imaging, confocal NIR fluorescent imaging, and CAFs isolation testing. The fibrotic phenotype down-regulation effects and in vitro CAFs killing effect of IR-780 were tested by qPCR, western blot, and flow cytometry. The in vivo therapeutic enhancement of anti-PD-L1 by IR-780 was evaluated on EMT6 and MC38 subcutaneous xenograft mice models. RESULTS: IR-780 has been demonstrated to be preferentially taken up by CAFs and accumulate in the mitochondria. Further results identified low-dose IR-780 to downregulate the fibrotic phenotype, while high-dose IR-780 could directly kill both CAFs and EMT6 cells in vitro. Moreover, IR-780 significantly inhibited extracellular matrix (ECM) protein deposition in the peri-tumoral stroma on subcutaneous EMT6 and MC38 xenografts, which increased the proportion of tumor-infiltrating lymphocytes (TILs) in the deep tumor and further promoted anti-PD-L1 therapeutic efficacy. CONCLUSION: This work provides a unique strategy for the inhibition of ECM protein deposition in the tumor microenvironment by targeted regulating of CAFs, which destroys the T cell barrier and further promotes tumor response to PD-L1 monoclonal antibody. IR-780 has been proposed as a potential therapeutic small-molecule adjuvant to promote the effect of immunotherapy.


Assuntos
Fibroblastos Associados a Câncer , Imunoterapia , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Animais , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia , Camundongos , Humanos , Imunoterapia/métodos , Microambiente Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Indóis/farmacologia , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Food Funct ; 15(10): 5527-5538, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38700280

RESUMO

The salty oligopeptides from Stropharia rugosoannulata have been proven to be potential ACE inhibitors. To investigate the ACE receptor binding properties and interaction mechanisms of salty oligopeptides, the molecular interaction, dynamics simulation, and antihypertensive evaluation cross-validation strategy were employed to reveal the oligopeptides' binding reactions and modes with the ACE receptor. Single oligopeptide (ESPERPFL, KSWDDFFTR) had exothermic and specific binding reactions with the ACE receptor, driven by hydrogen bonds and van der Waals forces. The coexistence of the multiple oligopeptide molecules did not produce the apparent ACE receptor competition binding reactions. The molecular dynamics simulation verified that the two oligopeptides disturbed the ACE receptor's different residue regions. Both oligopeptides could form stable complexes with the ACE receptor. Based on the classification of 50 oligopeptides' binding modes, ESPERPFL and KSWDDFFTR belonged to different classes, and their receptor binding modes and sites complemented, resulting in a potential synergistic effect on ACE inhibition. The antihypertensive effect of KSWDDFFTR and its distribution in the body were evaluated using SHR rats orally and ICR mice by tail vein injection, and KSWDDFFTR had antihypertensive effects within 8 h. The study provides a theoretical basis for understanding salty oligopeptides' ACE receptor binding mechanism and their antihypertensive effects.


Assuntos
Anti-Hipertensivos , Simulação de Dinâmica Molecular , Oligopeptídeos , Animais , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/química , Ratos , Masculino , Peptidil Dipeptidase A/metabolismo , Peptidil Dipeptidase A/química , Agaricales/química , Agaricales/metabolismo , Camundongos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Ligação Proteica , Pressão Sanguínea/efeitos dos fármacos , Ratos Endogâmicos SHR
9.
Burns Trauma ; 12: tkad045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444637

RESUMO

Background: Ionizing radiation (IR)-induced intestinal injury is a major side effect and dose-limiting toxicity in patients receiving radiotherapy. There is an urgent need to identify an effective and safe radioprotectant to reduce radiation-induced intestinal injury. Immunoregulation is considered an effective strategy against IR-induced injury. The purpose of this article was to investigate the protective effect of Nocardia rubra cell wall skeleton (Nr-CWS), an immunomodulator, on radiation-induced intestinal damage and to explore its potential mechanism. Methods: C57BL/6 J male mice exposed to 12 Gy whole abdominal irradiation (WAI) were examined for survival rate, morphology and function of the intestine and spleen, as well as the gut microbiota, to comprehensively evaluate the therapeutic effects of Nr-CWS on radiation-induced intestinal and splenetic injury. To further elucidate the underlying mechanisms of Nr-CWS-mediated intestinal protection, macrophages were depleted by clodronate liposomes to determine whether Nr-CWS-induced radioprotection is macrophage dependent, and the function of peritoneal macrophages stimulated by Nr-CWS was detected in vitro. Results: Our data showed that Nr-CWS promoted the recovery of intestinal barrier function, enhanced leucine-rich repeat-containing G protein-coupled receptor 5+ intestinal stem cell survival and the regeneration of intestinal epithelial cells, maintained intestinal flora homeostasis, protected spleen morphology and function, and improved the outcome of mice exposed to 12 Gy WAI. Mechanistic studies indicated that Nr-CWS recruited macrophages to reduce WAI-induced intestinal damage. Moreover, macrophage depletion by clodronate liposomes blocked Nr-CWS-induced radioprotection. In vitro, we found that Nr-CWS activated the nuclear factor kappa-B signaling pathway and promoted the phagocytosis and migration ability of peritoneal macrophages. Conclusions: Our study suggests the therapeutic effect of Nr-CWS on radiation-induced intestinal injury, and provides possible therapeutic strategy and potential preventive and therapeutic drugs to alleviate it.

10.
Food Chem ; 420: 136090, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37080114

RESUMO

The purpose of this study was to explore the effect of continuous enzymolysis on the umami characteristics of Lentinula edodes and illuminate the umami mechanism of peptides. The results indicated that the continuous enzymolysis extracts (LFTE) of L.edodes had higher umami intensity and palatability than the water extracts (LWE). 1H NMR and LC-MS/MS were used to evaluate taste metabolites and peptide profiles. Among the identified peptides, LPGVAE, LDELEK, DVELSK, LPDEAR, and TTLPDK with high umami scores which threshold in the range of 0.091-0.371 mmol/L were screened by iUmami-SCM and BIOPEP-UWM, and further verified by sensory evaluation. The results of molecular docking suggested that Ser148, Asn150, Ser276, Ser278 of T1R1 and Asn68, Val277, Ala302, Ser306 of T1R3 played a key role in the umami peptides docking. The study revealed continuous enzymolysis of L.edodes could obtain more umami substances and umami peptides, which laid a foundation for researching flavor substances and developing flavor products from L.edodes.


Assuntos
Cogumelos Shiitake , Cogumelos Shiitake/metabolismo , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/metabolismo , Cromatografia Líquida , Paladar , Espectrometria de Massas em Tandem , Peptídeos/química
11.
Int J Biol Macromol ; 251: 126388, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37595717

RESUMO

This study demonstrated the effects of semi-solid enzymolysis on physicochemical properties of fruiting body powders and polysaccharides from Hericium erinaceus and protective effects on gastric mucosal injury. Semi-solid enzymolysis could reduce the particle size, change the microstructure of fruiting body powders, increase the contents of soluble polysaccharide (26.26-67.04 %) and uronic acid (16.97-31.12 %) and reduce the molecular weight of polysaccharides. The digestibility of fruiting body powder of H. erinaceus after semi-solid enzymolysis was increased by 31.4 %, compared with that of the fruiting body powder of H. erinaceus without enzymolysis. Semi-solid enzymolysis could enhance the protective effects of the fruiting body powders and polysaccharides on ethanol-induced human gastric mucosal epithelial cells (GES-1) cells, increase the production of superoxide dismutase (SOD, 0-37.33 %) and catalase (CAT, 2.47-18.46 %), and inhibit the production of malonaldehyde (MDA, 2.45-19.62 %), myeloperoxidase (MPO, 0-13.54 %), interleukin (IL-6, 4.39-24.62 %) and tumor necrosis factor-α (TNF-α, 5.97-12.25 %). Semi-solid enzymolysis could improve the inhibition rate of the fruiting body powder on gastric ulcer (32.70-46.26 %), inhibit oxidative stress and inflammation, and protect rats with acute gastric mucosal injury against the stimulation of ethanol on gastric mucosa. In conclusion, semi-solid enzymolysis may enhance the protective effects of the fruiting body powders and polysaccharides on gastric mucosal injury.

12.
Int J Biol Macromol ; 224: 1509-1523, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36550792

RESUMO

A proteoglycan LEPS1 was firstly isolated and purified from the spent substrate of Lentinula edodes, an agricultural waste that may cause environmental pollution. The average molecular weight of LEPS1 was 1.18 × 104 g/mol, and carbohydrate moiety (88.9 %) was composed of glucose, arabinose, galactose, xylose and mannose at a molar ratio of 1.2:1.2:1.0:2.3:1.1. The protein moiety (8.5 %) of LEPS1 was bonded to the polysaccharide chain via O-glycosidic linkage. LEPS1 could significantly improve the inflammatory injury of LPS stimulated RAW264.7 macrophages by inhibiting the secretion of NO and decreasing the levels of pro-inflammatory factors (TNF-α, IL-1ß and IL-6). LEPS1 inhibited JAK-STAT1 and p38 MAPK signaling pathway via modulating JAK expression, phosphorylation of STAT1 and phosphorylation of p38, respectively. Moreover, LEPS1 could promote the expression of CD 206 and IL-10 which were the markers for repairing macrophages. Overall, LEPS1 had anti-inflammatory activity and can potentially treat as a novel anti-inflammation agent. This work could provide scientific basis and valuable information for the highly efficient utilization of spent L. edodes substrates as the by-product in mushroom industries.


Assuntos
Cogumelos Shiitake , Cogumelos Shiitake/química , Proteoglicanas/metabolismo , Polissacarídeos/química , Anti-Inflamatórios/química , Macrófagos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo
13.
Brain Res ; 1805: 148285, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36801209

RESUMO

Radiation-induced brain injury (RIBI) is a common complication of radiation therapy for brain tumors. Vascular damage is one of the key factors closely related to the severity of the RIBI. However, effective vascular target treatment strategies are lacking. Previously, we have identified a fluorescent small molecule dye, IR-780, which shows the properties of injury tissue targeting and provided protection against various injuries by modulating oxidative stress. This study aims to validate the therapeutic effect of IR-780 on RIBI. The effectiveness of IR-780 against RIBI has been comprehensively evaluated through techniques such as behavior, immunofluorescence staining, quantitative real-time polymerase chain reaction, Evans Blue leakage experiments, electron microscopy, and flow cytometry. Results show that IR-780 improves cognitive dysfunction, reduces neuroinflammation, restores the expression of tight junction proteins in the blood-brain barrier (BBB), and promotes the recovery of BBB function after whole brain irradiation. IR-780 also accumulates in injured cerebral microvascular endothelial cells, and its subcellular location is in the mitochondria. More importantly, IR-780 can reduce the levels of cellular reactive oxygen species and apoptosis. Moreover, IR-780 has no significant toxic side effects. IR-780 alleviates RIBI by protecting vascular endothelial cells from oxidative stress, reducing neuroinflammation, and restoring BBB function, suggesting IR-780 as a promising treatment candidate for RIBI therapy.


Assuntos
Lesões Encefálicas , Células Endoteliais , Humanos , Células Endoteliais/metabolismo , Doenças Neuroinflamatórias , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Barreira Hematoencefálica/metabolismo , Mitocôndrias/metabolismo
14.
Food Funct ; 14(5): 2374-2384, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36779533

RESUMO

Sanghuangporus baumii, an edible fungus rich in heteropolysaccharides, has been found to have some anti-cervical cancer effects. In the current study, the effects of an aqueous extract of S. baumii on cervical cancer were investigated in a U14 cervical carcinoma cell implanted female Kunming mouse model. An aqueous extract of S. baumii (SHWE) was administered to tumor-bearing mice by gavage for 21 days. SHWE treatment significantly inhibited tumor growth by 67.4% at a dose of 400 mg per kg bodyweight. Transcriptomic results showed that the expression of key genes GABARAP, VMP1, VAMP8 and STX17 which are involved in the autophagy pathway was regulated after SHWE treatment, suggesting that SHWE may induce autophagy in tumors. The results were further confirmed by measuring the LC3II/LC3I ratio using western blotting. Moreover, some differentially expressed genes were involved in the insulin signaling pathway, implying that SHWE induced autophagy by disturbing glucose uptake and utilization in tumors. The analysis of the gut microbiota indicated that SHWE treatment stimulated the proliferation of Akkermansia, a well-known probiotic that presented benefits in metabolic regulation and cancer therapy. In conclusion, SHWE administration modified the gut microbiota, disturbed the glucose metabolism and induced autophagy in tumors, and then inhibited the development of cervical carcinoma in vivo.


Assuntos
Basidiomycota , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Transdução de Sinais , Proliferação de Células , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Autofagia , Apoptose , Linhagem Celular Tumoral , Proteínas de Membrana/farmacologia
15.
Burns Trauma ; 11: tkad001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37188110

RESUMO

Background: Radiation ulcers are a common and severe injury after uncontrolled exposure to ionizing radiation. The most important feature of radiation ulcers is progressive ulceration, which results in the expansion of radiation injury to the nonirradiated area and refractory wounds. Current theories cannot explain the progression of radiation ulcers. Cellular senescence refers to as irreversible growth arrest that occurs after exposure to stress, which contributes to tissue dysfunction by inducing paracrine senescence, stem cell dysfunction and chronic inflammation. However, it is not yet clear how cellular senescence facilitates the continuous progression of radiation ulcers. Here, we aim to investigate the role of cellular senescence in promoting progressive radiation ulcers and indicate a potential therapeutic strategy for radiation ulcers. Methods: Radiation ulcer animal models were established by local exposure to 40 Gy X-ray radiation and continuously evaluated for >260 days. The roles of cellular senescence in the progression of radiation ulcers were assessed using pathological analysis, molecular detection and RNA sequencing. Then, the therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells (uMSC-CM) were investigated in radiation ulcer models. Results: Radiation ulcer animal models with features of clinical patients were established to investigate the primary mechanisms responsible for the progression of radiation ulcers. We have characterized cellular senescence as being closely associated with the progression of radiation ulcers and found that exogenous transplantation of senescent cells significantly aggravated them. Mechanistic studies and RNA sequencing suggested that radiation-induced senescent cell secretions were responsible for facilitating paracrine senescence and promoting the progression of radiation ulcers. Finally, we found that uMSC-CM was effective in mitigating the progression of radiation ulcers by inhibiting cellular senescence. Conclusions: Our findings not only characterize the roles of cellular senescence in the progression of radiation ulcers but also indicate the therapeutic potential of senescent cells in their treatment.

16.
Foods ; 12(18)2023 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-37761171

RESUMO

Undecapeptide is the central peptide molecule in the peptide base material of Stropharia rugosoannulata, and angiotensin-converting enzyme (ACE) plays a crucial role in hypertension. To fully explore the interaction mechanism and ACE-inhibitory activity of long-chain peptides from Stropharia rugosoannulata, the binding conformations of twenty-seven undecapeptides with the ACE receptor were revealed by molecule docking. The undecapeptide GQEDYDRLRPL with better receptor binding capacity and higher secondary mass spectral abundance was screened. All amino acid residues except proline in GQEDYDRLRPL interacted with the ACE receptor. GQEDYDRLRPL interfered with the receptor's overall structure, with significant fluctuations in amino acid residues 340-355, including two residues in the receptor's active pockets. The binding constants of GQEDYDRLRPL to the ACE receptors were at the µM level, with a kinetic binding constant of 9.26 × 10-7 M, which is a strong binding, and a thermodynamic binding constant of 3.06 × 10-6 M. Intermolecular interaction were exothermic, enthalpy-driven, and specific binding reactions. GQEDYDRLRPL had an IC50 value of 164.41 µmol/L in vitro and superior antihypertensive effects at low-gavage administration in vivo. Obtaining information on the interaction mechanism of ACE-inhibitory undecapeptides from S. rugosoannulata with the ACE receptor will help to develop and utilize ACE inhibitors of natural origin.

17.
Front Nutr ; 9: 960218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967776

RESUMO

This study identified the peptides in the fermentation mycelia of Stropharia rugosoannulata. The molecular weight of the peptides was below 3,000 Da. Heptapeptides to decapeptides were the main peptides in the fermentation mycelia of S. rugosoannulata. More than 50% of the peptides had salty and umami taste characteristics, and the long-chain peptides (decapeptides to 24 peptides) also played an essential role in the pleasant taste characteristics of mycelium. In the salty and umami peptide of S. rugosoannulata, the distribution of non-polar hydrophobic amino acids and polar-uncharged amino acids accounted for a relatively high proportion, and the proportion of polar-uncharged amino acids further increased, with the extension of the peptide chain. P, F, I, l, V, G, S, T, and D were the amino acids with a high proportion in the peptides. The taste peptides can bind to more than 60% of the active amino acid residues in the cavity-binding domain of the T1R1/T1R3 receptors. Hydrogen bond interaction was the primary mode of interaction between the peptides and the receptor. The first and second amino acid residues (such as S, V, E, K, G, and A) at the C-terminal and N-terminal of the peptides were easy to bind to T1R1/T1R3 receptors. Asp108, Asn150, Asp147, Glu301, Asp219, Asp243, Glu70, Asp218 in T1R1, and Glu45, Glu148, Glu301, Glu48, and Ala46 in TIR3 were the key active amino acid sites of taste peptides binding to T1R1/T1R3 receptors.

18.
Food Chem ; 393: 133378, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35667179

RESUMO

In this paper, the changes of non-volatile taste substances and the formation mechanism of taste quality of Lentinula edodes during hot air drying at 50 °C were studied. The results showed that with the increase of drying time, the moisture content gradually decreased, volume shrinkage, color deepening, chewiness and viscosity first increased and then decreased. After drying for 8 h, when the moisture content reached 28.68%, the appearance, taste and the overall quality of L.edodes were better. After 12 h drying, the content of free amino acids and organic acids increased significantly, while the content of 5'-nucleotide and soluble sugar decreased significantly, and the EUC value was higher. Succinic acid has the highest TAV value, which contributes the most to the taste of dried L.edodes products. Comprehensive quality analysis of drying process and the guidance for rehydration of dried L.edodes were also predicted.


Assuntos
Cogumelos Shiitake , Dessecação/métodos , Cogumelos Shiitake/química , Paladar
19.
Ultrason Sonochem ; 88: 106074, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35753137

RESUMO

To reveal the structural characteristics and angiotensin-converting enzyme (ACE) inhibition mechanism of Stropharia rugosoannulata mushroom peptides prepared by multifrequency ultrasound, the peptide distribution, amino acid sequence composition characteristics, formation pathway, and ACE inhibition mechanism of S. rugosoannulata mushroom peptides were studied. It was found that the peptides in S. rugosoannulata mushroom samples treated by multifrequency ultrasound (probe ultrasound and bath ultrasound mode) were mainly octapeptides, nonapeptides, and decapeptides. Hydrophobic amino acids were the primary amino acids in the peptides prepared by ultrasound, and the amino acid dissociation of the peptide bonds at the C-terminal under the action of ultrasound was performed mainly to produce hydrophobic amino acids. Pro and Val (PV), Arg and Pro (RP), Pro and Leu (PL), and Asp (D) combined with hydrophobic amino acids were the characteristic amino acid sequence basis of the active peptides of the S. rugosoannulata mushroom. The docking results of active peptides and ACE showed that hydrogen bond interaction remained the primary mode of interaction between ACE and peptides prepared by ultrasound. The peptides can bind to the amino acid residues in the ACE active pocket, zinc ions, or key amino acids in the domain, and this results in inhibition of ACE activity. Cation-pi interactions also played an important role in the binding of mushroom peptides to ACE. This study explains the structural characteristics and ACE inhibition mechanism used by S. rugosoannulata mushroom peptides prepared by ultrasound, and it will provide a reference for the development and application of S. rugosoannulata mushroom peptides.


Assuntos
Agaricales , Inibidores da Enzima Conversora de Angiotensina , Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Angiotensinas , Simulação de Acoplamento Molecular , Peptídeos/química
20.
Food Res Int ; 162(Pt B): 112051, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461385

RESUMO

The transcriptome and metabolome analyses revealed the differentially expressed metabolites (DEMs) and genes (DEGs) in the dried Lentinula edodes' response to heat treatment. Most DEMs between the L.edodes sample groups were lipids and lipid-like molecules, nucleosides, nucleotides, analogs, and organic acids and derivatives. DEMs enrich the pathway of the TCA cycle, alanine, aspartate, glutamate metabolism, and arginine biosynthesis. The proportion of DEGs annotation in the metabolism pathway and the number of DEGs increased within the drying process of 2 h. The DEGs were annotated in the signal transduction and amino acid metabolism pathways during the drying process of 2 h âˆ¼ 3 h. Five DEGs including LE01Gene04306, LE01Gene06275, LE01Gene11513, LE01Gene13848 and LE01Gene13853 existed in all comparative groups. Twenty-nine DEMs marker can be used for monitoring the quality of L.edodes during drying. The metabolic pathways, secondary metabolites biosynthesis, and unsaturated fatty acid biosynthesis were the landmark pathways that monitor DEMs and DEGs, and gamma-linolenic acid was a signal DEM marker. It provides new insights for understanding the flavor formation of L.edodes during the hot-air drying process.


Assuntos
Cogumelos Shiitake , Cogumelos Shiitake/genética , Transcriptoma , Temperatura Alta , Metabolômica , Metaboloma
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