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1.
J Dent ; 143: 104876, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367826

RESUMO

OBJECTIVE: This study evaluated the effect of administration of trans-resveratrol-containing orodispersible tablets on the protein composition of the AEP and on blood plasma trans-resveratrol concentrations. METHODS: Ten volunteers participated in two crossover double-blind phases. In each phase, after dental prophylaxis, they received a trans-resveratrol (15 mg) orodispersible tablet, or a placebo tablet (without actives). The AEP formed after 120 min was collected with electrode filter papers soaked in 3 % citric acid. Blood samples were collected 30, 45, 60 and 120 min after the use of the tablet. After protein extraction, AEP samples were analyzed by shotgun labelfree quantitative proteomics and plasma samples were analyzed by high-performance liquid chromatography (HPLC). RESULTS: Eight hundred and two proteins were identified in the AEP. Among them, 336 and 213 were unique to the trans-resveratrol and control groups, respectively, while 253 were common to both groups. Proteins with important functions in the AEP had increased expression in the trans-resveratroltreated group, such as neutrophil defensins, S100 protein isoforms, lysozyme C, cystatin-D, mucin-7, alphaamylase, albumin, haptoglobin and statherin. Trans-resveratrol was detected in the plasma at all the times evaluated, with the peak at 30 min. CONCLUSIONS: The administration of trans-resveratrol in sublingual orodispersible tablets was effective both to increase the bioavailability of the polyphenol and the expression of antibacterial and acid-resistant proteins in the AEP, which might benefit oral and general health.


Assuntos
Proteínas , Humanos , Película Dentária , Resveratrol/farmacologia , Resveratrol/análise , Resveratrol/metabolismo , Proteínas/análise , Proteínas/metabolismo , Proteínas/farmacologia
2.
Int J Biol Macromol ; 262(Pt 1): 129826, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296124

RESUMO

Fresh fruits are highly needed for the health benefits of human beings because of the presence of high content of natural nutrition in the form of vitamins, minerals, antioxidants, and other phenolic compounds. However, some nutritional fruits such as guava are climacteric in nature with very less post-harvest shelf-life because of the ripening in a very short period and possibility of microbial infections. Thus security of natural nutrients is a serious concern in order to properly utilize guava without generating a huge amount of waste. Among reported various methods for the enhancement of fruits shelf-life, the application of edible coatings with antimicrobial activities on the outer surface of fruits have attracted significant attention because of their eco-friendly nature, easy applicability, high efficacy, and good durability. In recent years, researchers are paying more and more attention in the development of antimicrobial edible coatings to enhance the post-harvest shelf-life of guava using polysaccharides, protein and lipids. In this review, basic approaches and recent advancements in development of antimicrobial and edible coatings on guava fruit by the application of polysaccharides and protein and lipids along with the combination of nanomaterials are summarized. In addition, improvements in basic properties of edible coatings to significantly control the permeation of gases (O2/CO2) by the optimization of coating components as well as delay in ripening process are reviewed and discussed.


Assuntos
Anti-Infecciosos , Filmes Comestíveis , Psidium , Humanos , Frutas , Conservação de Alimentos/métodos , Polissacarídeos/farmacologia , Anti-Infecciosos/farmacologia , Proteínas/farmacologia , Lipídeos/farmacologia
3.
Clin Genitourin Cancer ; 22(1): e106-e112.e4, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37673783

RESUMO

INTRODUCTION: Mild Leydig cell insufficiency affects a substantial proportion of testicular cancer survivors. Previous studies have not shown a beneficial effect of testosterone replacement therapy, however, with a pronounced interindividual effect. Thus, biomarkers identifying the subgroups that might benefit are wanted. We aimed to determine if insulin-like factor 3 (INSL3), basal and human chorionic gonadotropin (hCG)-stimulated testosterone can predict the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig cell insufficiency. PATIENTS AND METHODS: We randomized adult testicular cancer survivors with mild Leydig cell insufficiency 1:1 to 12 months of transdermal testosterone replacement therapy (Tostran gel 2%) or placebo. INSL3, basal, and hCG-stimulated testosterone were measured at baseline. Outcomes (glucose, insulin, HbA1C, lipids, blood pressure, and body composition) were measured at baseline, 6 and 12 months. We applied a linear mixed-effect model comparing patients receiving testosterone with placebo in subgroups by biomarker. RESULTS: We included and randomized 69 patients between October 2016 and February 2018. Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had a -1.7 kg (95% CI: -3.1, -0.4) and -2.0 kg (95% CI: -3.5, -0.6) change in fat mass after 12 months of testosterone replacement therapy compared with placebo. This was not the case in patients with INSL3 and hCG-stimulated testosterone above the median. We did not find any effect of these biomarkers on glucose, insulin, HbA1c, or lipids. CONCLUSION: Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had decreased fat mass after 12 months of testosterone replacement therapy compared with placebo. It should be evaluated in larger trials if these biomarkers can be used as predictive markers identifying testicular cancer patients with mild Leydig cell insufficiency who might benefit from testosterone substitution.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Testosterona , Masculino , Adulto , Humanos , Células Intersticiais do Testículo , Neoplasias Testiculares/tratamento farmacológico , Hemoglobinas Glicadas , Proteínas/farmacologia , Gonadotropina Coriônica , Insulina/uso terapêutico , Insulina/farmacologia , Biomarcadores , Sobreviventes , Glucose/farmacologia , Lipídeos/farmacologia
4.
Breast Cancer Res ; 25(1): 144, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968653

RESUMO

BACKGROUND: Breast cancer stem cells (BCSCs) are resistant to standard therapies, facilitate tumor dissemination, and contribute to relapse and progression. Super-enhancers are regulators of stemness, and BET proteins, which are critical for super-enhancer function, are a potential therapeutic target. Here, we investigated the effects of BET proteins on the regulation of breast cancer stemness using the pan-BET degrader ZBC260. METHODS: We evaluated the effect of ZBC260 on CSCs in TNBC cell lines. We assessed the effect of ZBC260 on cellular viability and tumor growth and measured its effects on cancer stemness. We used RNA sequencing and stemness index to determine the global transcriptomic changes in CSCs and bulk cells and further validated our findings by qPCR, western blot, and ELISA. RESULTS: ZBC260 potently inhibited TNBC growth both in vitro and in vivo. ZBC260 reduced stemness as measured by cell surface marker expression, ALDH activity, tumorsphere number, and stemness index while increasing differentiated cells. GSEA analysis indicated preferential downregulation of stemness-associated and inflammatory genes by ZBC260 in ALDH+ CSCs. CONCLUSIONS: The BET degrader ZBC260 is an efficient degrader of BET proteins that suppresses tumor progression and decreases CSCs through the downregulation of inflammatory genes and pathways. Our findings support the further development of BET degraders alone and in combination with other therapeutics as CSC targeting agents.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , Proteínas/metabolismo , Proteínas/farmacologia , Proteínas/uso terapêutico , Transformação Celular Neoplásica/metabolismo , Diferenciação Celular/genética , Células-Tronco Neoplásicas/patologia
5.
Food Res Int ; 174(Pt 1): 113499, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986414

RESUMO

Antarctic krill suffers from severe water loss after heating, and its quality deteriorates, so it is in urgent need of a green and healthy improver. In this paper, the effects of L-arginine (L-Arg) soaking on the modification of the quality of heat-treated Antarctic krill and the structure of myofibrillar proteins (MPs) in Antarctic krill were investigated. The results showed that L-Arg had an ameliorating effect on heat-treated krill in a concentration-dependent relationship. The water-holding capacity of L-Arg-soaked krill was 1.41 times higher than that of sodium tripolyphosphate (STPP) at an equivalent concentration (80 mM). At 120 mM L-Arg soaked, L* and hardness of krill decreased to 58.31 and 334.81 g, while resilience and moisture content increased to 0.47 and 85.29 % after heating, respectively. The scanning electron microscopy (SEM) results revealed that the tissue state of the pH-corrected groups was better than the control, but not as well as that of the pH-uncorrected groups. pH and the guanidinium group in L-Arg both played roles in promoting the transition of MPs from disordered to ordered secondary structures. This transition reduced the exposure of hydrophobic and sulfhydryl groups in MPs, inhibited the protein aggregation and increased the solubility of MPs to 71.61 %, which ultimately improved the quality of heat-treated krill. It is worth noting that the pH effect had a primary influence on the observed effects, while the guanidinium group made a secondary contribution. These results could broaden the potential application of L-Arg as an improver of the quality of heat-treated krill.


Assuntos
Euphausiacea , Temperatura Alta , Animais , Euphausiacea/química , Guanidina/farmacologia , Proteínas/farmacologia , Concentração de Íons de Hidrogênio , Água
6.
J Transl Med ; 21(1): 723, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37840135

RESUMO

BACKGROUND: Extracellular vesicles (EV) are considered a cell-free alternative to mesenchymal stromal cell (MSC) therapy. Numerous reports describe the efficacy of EV in conferring immunomodulation and promoting angiogenesis, yet others report these activities to be conveyed in EV-free bioproducts. We hypothesized that this discrepancy may depend either on the method of isolation or rather the relative impact of the individual bioactive components within the MSC secretome. METHODS: To answer this question, we performed an inter-laboratory study evaluating EV generated from adipose stromal cells (ASC) by either sequential ultracentrifugation (UC) or size-exclusion chromatography (SEC). The effect of both EV preparations on immunomodulation and angiogenesis in vitro was compared to that of the whole secretome and of the EV-free protein fraction after SEC isolation. RESULTS: In the current study, neither the EV preparations, the secretome or the protein fraction were efficacious in inhibiting mitogen-driven T cell proliferation. However, EV generated by SEC stimulated macrophage phagocytic activity to a similar extent as the secretome. In turn, tube formation and wound healing were strongly promoted by the ASC secretome and protein fraction, but not by EV. Within the secretome/protein fraction, VEGF was identified as a potential driver of angiogenesis, and was absent in both EV preparations. CONCLUSIONS: Our data indicate that the effects of ASC on immunomodulation and angiogenesis are EV-independent. Specific ASC-EV effects need to be dissected for their use as cell-free therapeutics.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Adipócitos , Células-Tronco Mesenquimais/metabolismo , Cicatrização , Vesículas Extracelulares/metabolismo , Proteínas/farmacologia
7.
Sci Rep ; 13(1): 17465, 2023 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-37838763

RESUMO

To further explore the pharmacological effect of pachymaran, this article studied the inhibition of pachymaran on oxidative stress and genetic damage induced by formaldehyde. 40 adult Kunming male mice were randomly divided into four groups with different interventions. One week later, the contents of serum SOD, GR, MDA, DNA-protein crosslink (DPC), 8-hydroxydeoxyguanosine (8-OHDG) and DNA adduct were determined by ELISA. The results showed that there were statistically significant differences in the contents of SOD, GR and MDA among the four groups (P < 0.01). The activity of SOD and GR increased along with the increase of pachymaran dosage (SOD: rs = 0.912, P < 0.01; GR: rs = 0.857, P < 0.01), while the content of MDA showing a significant negative correlation (rs = - 0.893, P < 0.01). There were statistically significant differences in the levels of DPC, 8-OHDG and DNA adduct among the four groups (DPC and DNA adduct: P < 0.01, 8-OHDG: P < 0.05), the concentration decreased along with the increase of pachymaran dosage (DPC: rs = - 0.855, P < 0.01; 8-OHDG:rs = - 0.412, P < 0.05, DNA adduct: γs = - 0.869, P < 0.01). It can be inferred that pachymaran can inhibit oxidative stress and DNA damage induced by formaldehyde with the dose-effect relationship.


Assuntos
Adutos de DNA , Dano ao DNA , Camundongos , Animais , Masculino , Adutos de DNA/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Estresse Oxidativo , Formaldeído/toxicidade , Proteínas/farmacologia , Superóxido Dismutase/metabolismo , Desoxiguanosina
9.
J Transl Med ; 21(1): 480, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464413

RESUMO

Bone regeneration therapy is clinically important, and targeted regulation of endoplasmic reticulum (ER) stress is important in regenerative medicine. The processing of proteins in the ER controls cell fate. The accumulation of misfolded and unfolded proteins occurs in pathological states, triggering ER stress. ER stress restores homeostasis through three main mechanisms, including protein kinase-R-like ER kinase (PERK), inositol-requiring enzyme 1ɑ (IRE1ɑ) and activating transcription factor 6 (ATF6), collectively known as the unfolded protein response (UPR). However, the UPR has both adaptive and apoptotic effects. Modulation of ER stress has therapeutic potential for numerous diseases. Repair of bone defects involves both angiogenesis and bone regeneration. Here, we review the effects of ER stress on osteogenesis and angiogenesis, with emphasis on ER stress under high glucose (HG) and inflammatory conditions, and the use of ER stress inducers or inhibitors to regulate osteogenesis and angiogenesis. In addition, we highlight the ability for exosomes to regulate ER stress. Recent advances in the regulation of ER stress mediated osteogenesis and angiogenesis suggest novel therapeutic options for bone defects.


Assuntos
Endorribonucleases , Proteínas Serina-Treonina Quinases , Proteínas Serina-Treonina Quinases/metabolismo , Endorribonucleases/metabolismo , Osteogênese , Transdução de Sinais , Apoptose , Estresse do Retículo Endoplasmático , Resposta a Proteínas não Dobradas , Proteínas/farmacologia , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo , eIF-2 Quinase/farmacologia
10.
FEBS J ; 290(18): 4465-4479, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37171222

RESUMO

Death-associated protein kinase 1 (DAPK1), a Ca2+/calmodulin-regulated serine/threonine kinase, regulates cell apoptosis and autophagy and has been implicated in the pathogenesis of Alzheimer's disease (AD). Targeting DAPK1 may be a promising approach for treating AD. In our previous study, we found that a natural polyphenol, resveratrol (1), is a moderate DAPK1 inhibitor. In the present study, we investigated the interactions between natural and synthetic derivatives of 1 and DAPK1. Binding assays including intrinsic fluorescence quenching, protein thermal shift and isothermal titration calorimetry indicated that oxyresveratrol (3), a hydroxylated derivative, and pinostilbene (5), a methoxylated derivative, bind to DAPK1 with comparable affinity to 1. The enzymatic assay showed that 3 more effectively inhibits the intrinsic ATPase activity of DAPK1 compared with 1. Crystallographic analysis revealed that the binding modes of the methoxylated derivatives were different from those of 1 and 3, resulting in a unique interaction. Our results suggest that 3 may be helpful in treating AD and provide a clue for the development of promising DAPK1 inhibitors.


Assuntos
Doença de Alzheimer , Humanos , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/química , Resveratrol/farmacologia , Doença de Alzheimer/patologia , Apoptose , Proteínas/farmacologia
11.
Sci Total Environ ; 891: 164415, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37236442

RESUMO

Polybrominated diphenyl ethers (PBDEs) are one of the most used halogenated flame retardants worldwide, and exert neurotoxicity, reproductive toxicity, endocrine interference, and carcinogenic effects on organisms. However, there are insufficient studies on the physical and immune defense at the individual level of mussels under different food conditions. To explore the defense strategy and individual health status, the thick-shelled mussels Mytilus coruscus were exposed to different BDE-47 concentrations (0, 0.1 and 10 µg/L) and nutritional conditions (feeding and starvation) for 21 days. The results showed that BDE-47 exposure and starvation significantly decreased the number of byssus threads (NBT), adhesion, and condition index (CI) of mussels, whereas increased the reactive oxygen species (ROS) production and the combined stress further declined the CI. BDE-47 exposure and starvation induced decreased adhesive capability and healthy state along with oxidative lesions in mussels. The downregulation gene expression of foot adhesion proteins (mfp-2/3/4/5/6) under starvation or combined exposure also proved the reduced adhesion of mussels. However, up-regulated mfp-1 and pre-collagens proteins (preCOL-D/P/NG) indicated mussels would adjust energy allocation to enhance the strength and extensibility of byssal threads for compensating reduced adhesion and CI. As global climate change and organic pollution have dramatically impacted the ocean, hazardous substances and the fluctuated primary productivity have frequently co-occurred, which will affect the structure of coastal biomes and fishery production.


Assuntos
Retardadores de Chama , Mytilus , Animais , Éteres Difenil Halogenados/toxicidade , Mytilus/fisiologia , Proteínas/farmacologia , Ecossistema , Retardadores de Chama/toxicidade
12.
Int J Mol Sci ; 24(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36902365

RESUMO

Porcine epidemic diarrhea virus (PEDV), a member of the α-coronavirus genus, can cause vomiting, diarrhea, and dehydration in piglets. Neonatal piglets infected with PEDV have a mortality rate as high as 100%. PEDV has caused substantial economic losses to the pork industry. Endoplasmic reticulum (ER) stress, which can alleviate the accumulation of unfolded or misfolded proteins in ER, involves in coronavirus infection. Previous studies have indicated that ER stress could inhibit the replication of human coronaviruses, and some human coronaviruses in turn could suppress ER stress-related factors. In this study, we demonstrated that PEDV could interact with ER stress. We determined that ER stress could potently inhibit the replication of GⅠ, GⅡ-a, and GⅡ-b PEDV strains. Moreover, we found that these PEDV strains can dampen the expression of the 78 kDa glucose-regulated protein (GRP78), an ER stress marker, while GRP78 overexpression showed antiviral activity against PEDV. Among different PEDV proteins, PEDV non-structural protein 14 (nsp14) was revealed to play an essential role in the inhibition of GRP78 by PEDV, and its guanine-N7-methyltransferase domain is necessary for this role. Further studies show that both PEDV and its nsp14 negatively regulated host translation, which could account for their inhibitory effects against GRP78. In addition, we found that PEDV nsp14 could inhibit the activity of GRP78 promotor, helping suppress GRP78 transcription. Our results reveal that PEDV possesses the potential to antagonize ER stress, and suggest that ER stress and PEDV nsp14 could be the targets for developing anti-PEDV drugs.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Antivirais/farmacologia , Infecções por Coronavirus/veterinária , Chaperona BiP do Retículo Endoplasmático , Vírus da Diarreia Epidêmica Suína/fisiologia , Proteínas/farmacologia , Suínos , Doenças dos Suínos/virologia
13.
Mar Drugs ; 21(2)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36827135

RESUMO

Metallocarboxypeptidases are zinc-dependent peptide-hydrolysing enzymes involved in several important physiological and pathological processes. They have been a target of growing interest in the search for natural or synthetic compound binders with biomedical and drug discovery purposes, i.e., with potential as antimicrobials or antiparasitics. Given that marine resources are an extraordinary source of bioactive molecules, we screened marine invertebrates for new inhibitory compounds with such capabilities. In this work, we report the isolation and molecular and functional characterization of NpCI, a novel strong metallocarboxypeptidase inhibitor from the marine snail Nerita peloronta. NpCI was purified until homogeneity using a combination of affinity chromatography and RP-HPLC. It appeared as a 5921.557 Da protein with 53 residues and six disulphide-linked cysteines, displaying a high sequence similarity with NvCI, a carboxypeptidase inhibitor isolated from Nerita versicolor, a mollusc of the same genus. The purified inhibitor was determined to be a slow- and tight-binding inhibitor of bovine CPA (Ki = 1.1·× 10-8 mol/L) and porcine CPB (Ki = 8.15·× 10-8 mol/L) and was not able to inhibit proteases from other mechanistic classes. Importantly, this inhibitor showed antiplasmodial activity against Plasmodium falciparum in an in vitro culture (IC50 = 5.5 µmol/L), reducing parasitaemia mainly by inhibiting the later stages of the parasite's intraerythrocytic cycle whilst having no cytotoxic effects on human fibroblasts. Interestingly, initial attempts with other related proteinaceous carboxypeptidase inhibitors also displayed similar antiplasmodial effects. Coincidentally, in recent years, a metallocarboxypeptidase named PfNna1, which is expressed in the schizont phase during the late intraerythrocytic stage of the parasite's life cycle, has been described. Given that NpCI showed a specific parasiticidal effect on P. falciparum, eliciting pyknotic/dead parasites, our results suggest that this and related inhibitors could be promising starting agents or lead compounds for antimalarial drug discovery strategies.


Assuntos
Antimaláricos , Carboxipeptidases , Plasmodium falciparum , Animais , Bovinos , Humanos , Antimaláricos/farmacologia , Carboxipeptidases/antagonistas & inibidores , Plasmodium falciparum/efeitos dos fármacos , Proteínas/farmacologia , Caramujos/química , Suínos
14.
J Dent ; 131: 104454, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36781100

RESUMO

OBJECTIVES: To perform a differential analysis of the dentin soluble proteomic and assess the effects of tissue health state and protocol for protein extraction. We hypothesized the dentin soluble proteomic varies according to the tissue physiopathological state (intact vs. caries-affected) and protocol used to extract its proteins. METHODS: Dentin from freshly extracted non-carious and carious teeth were randomly assigned for protein extraction using either guanidine-HCl/ethylenediaminetetraacetic acid (EDTA) or acetic acid. Protein extracts from intact and caries-affected dentin were processed and digested with trypsin for shotgun label-free proteomic analysis (nLC-ESI-MS/MS). Peptides identification was performed on a nanoACQUITY UPLC-Xevo Q-Tof MS system. Peptides identified with scores of confidence greater than 95% were included in the quantitative statistical analysis embedded in the PLGS software. Differences between experimental conditions were calculated using Student test-t with significance pre-set at α=0.05. RESULTS: A total of 158 human proteins were identified. Approximately one-sixth of proteins (24/158) were present in at least two different extracts. Conversely, the greatest number of proteins (134/158) was identified uniquely in only one of the extracts. Overall, a larger number of soluble proteins was retrieved from caries-affected than intact dentin (86/158). Likewise, a greater number of proteins was extracted by the guanidine-HCl/EDTA (106/158) in comparison to acetic acid protocol. Several proteins detected in dentin extracts, mainly those from caries-affected teeth, are biological and/or metabolically involved with tissue turnover/remodeling. CONCLUSION: The identity/abundance of soluble proteins retrieved from and remained in dentin noticeably depend on this tissue physiopathological state and protocol used to remove its minerals. CLINICAL SIGNIFICANCE: The present findings brought new insight into the proteomic phenotype of human dentin and may provide targets for the development of novel caries disease-prevention therapies.


Assuntos
Cárie Dentária , Dentina , Humanos , Cárie Dentária/metabolismo , Ácido Edético/farmacologia , Guanidinas/metabolismo , Guanidinas/farmacologia , Proteínas/metabolismo , Proteínas/farmacologia , Proteômica , Espectrometria de Massas em Tandem
15.
Molecules ; 28(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36677965

RESUMO

Peptides, functional nutrients with a size between those of large proteins and small amino acids, are easily absorbed by the human body. Therefore, they are seeing increasing use in clinical medicine and have revealed immunomodulatory and anti-inflammatory properties which could make them effective in healing skin wounds. This review sorted and summarized the relevant literature about peptides during the past decade. Recent works on the extraction, modification and synthesis of peptides were reviewed. Importantly, the unique beneficial effects of peptides on the skin were extensively explored, providing ideas for the development and innovation of peptides and laying a knowledge foundation for the clinical application of peptides.


Assuntos
Peptídeos , Pele , Humanos , Peptídeos/farmacologia , Peptídeos/química , Proteínas/farmacologia , Cicatrização , Aminoácidos/farmacologia
16.
Chin J Nat Med ; 21(1): 36-46, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36641231

RESUMO

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Flavonoides/farmacologia , Proteínas/metabolismo , Proteínas/farmacologia , Sistema de Sinalização das MAP Quinases , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/farmacologia
18.
J Ethnopharmacol ; 304: 116052, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36529246

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pilose antler is a traditional Chinese medicine used to improve kidney function, strengthen tendons and bones, and prolong life, among other uses. It is widely employed in the treatment of osteoporosis. However, the molecular mechanisms underlying the treatment of high turnover osteoporosis are not fully understood. AIM OF THE STUDY: The present study aimed to investigate the molecular mechanism underlying pilose antler polysaccharide and polypeptide extracts in inhibiting bone resorption in high turnover osteoporosis, and compare the effects of the two components alone and in combination to explore whether they could produce synergistic enhancement effects. MATERIALS AND METHODS: The quantitative and qualitative characteristics of pilose antler polysaccharide and polypeptide extracts were detected by UV-visible spectrophotometry and high-performance liquid chromatography. A rat model of retinoic acid-induced osteoporosis was used to evaluate the inhibitory effect of the extracts on bone resorption. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of factors related to high turnover type osteoporosis in rat serum. Western blotting was used to detect the expression of proteins related to the MAKP and MMP-9 signaling pathways in rat femurs. Fluorescence quantitative PCR was used to detect the transcription levels of genes related to the MAKP and MMP-9 signaling pathways in rat femur tissues. Hematoxylin and eosin staining were used to observe the osteoprotective effects of pilose antler polysaccharides and polypeptides. RESULTS: The yield of pilose antler polysaccharides was 8.3%, and was mainly composed of mannose, glucosamine hydrochloride, glucuronic acid, Galacturonic acid, Galactose hydrochloride, glucose, and galactose. The yield of the polypeptides was 26.2%, and eighty percent of the molecular weight of the antler polypeptides was 1.6 kDa-7kD, among which, the molecular weight of 7kD peptide accounted for 52% of the total. Both polysaccharides and peptides could reduce the activities of TRACP, OCN, ERK1, JNK, and MMP-9 in rat serum and reduce both the protein expression and gene transcription levels of ERK1, JNK, and MMP-9 in rat femur tissue with significant differences compared with the model group. Both extracts exerted significant protective effects on rat femur tissue. The effect of pilose antler polypeptides alone was better than that of polysaccharides either alone or in combination. CONCLUSIONS: Pilose antler polysaccharides, polypeptides, and their mixtures could inhibit the occurrence of bone resorption of high turnover osteoporosis by stimulating the MAKP and MMP-9 signaling pathways to reduce the expression of the ERK1, JNK, and MMP-9 genes and proteins, and could help alleviate bone loss caused by retinoic acid. Pilose antler polypeptides had a stronger effect on inhibiting bone resorption. The combination of the two components did not show synergistic enhancement effect, and the polysaccharide tended to moderate the inhibitory enhancement effect of the polypeptide.


Assuntos
Reabsorção Óssea , Cervos , Osteoporose , Ratos , Animais , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Galactose , Osteoporose/metabolismo , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Proteínas/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Transdução de Sinais , Tretinoína/farmacologia , Tretinoína/uso terapêutico
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971662

RESUMO

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.


Assuntos
Humanos , Transdução de Sinais , Flavonoides/farmacologia , Proteínas/farmacologia , Sistema de Sinalização das MAP Quinases , Neoplasias Colorretais/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ciclo Celular/farmacologia
20.
Viruses ; 14(11)2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36366511

RESUMO

Porcine epidemic diarrhea virus (PEDV) infection causes huge economic losses to the pig industry worldwide. DNAJA3, a member of the Hsp40 family proteins, is known to play an important role in the replication of several viruses. However, it remains unknown if it interacts with PEDV. We found that DNAJA3 interacted with PEDV S1, initially with yeast two-hybrid screening and later with Co-IP, GST pull-down, and confocal imaging. Further experiments showed the functional relationship between DNAJA3 and PEDV in the infected IPEC-J2 cells. DNAJA3 overexpression significantly inhibited PEDV replication while its knockdown had the opposite effect, suggesting that it is a negative regulator of PEDV replication. In addition, DNAJA3 expression could be downregulated by PEDV infection possibly as the viral strategy to evade the suppressive role of DNAJA3. By gene silencing and overexpression, we were able to show that DNAJA3 inhibited PEDV adsorption to IPEC-J2 cells but did not affect virus invasion. In conclusion, our study provides clear evidence that DNAJA3 mediates PEDV adsorption to host cells and plays an antiviral role in IPEC-J2 cells.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Suínos , Animais , Chlorocebus aethiops , Vírus da Diarreia Epidêmica Suína/genética , Adsorção , Replicação Viral , Células Vero , Proteínas/farmacologia
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