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2.
Artigo em Inglês | MEDLINE | ID: mdl-38615671

RESUMO

Introduction This study evaluated the phenotypic and pathology characteristics of patients undergoing kidney biopsy at a single center, while also determining the frequency and factors associated with clinical outcomes. Methods The incidence and distribution of biopsy-proven kidney diseases in 2000-2019 were surveyed. Consecutive individuals diagnosed with membranous nephropathy (MN), immunoglobulin A nephropathy (IgAN), and minimal change disease (MCD) between August 2015 and December 2019 were enrolled in the prospective two-year follow-up study. Outcomes included remission of proteinuria and kidney disease progression events. Multivariable adjusted Cox proportional hazards model was applied. Results 4,550 kidney biopsies were performed in 2000-2019, showing a noticeable increase in the proportion of MN. 426 patients were enrolled in follow-up cohort. 346 (81.2%) achieved remission of proteinuria, 39 (9.2%) suffered kidney disease progression and 51.3% of them were diagnosed with IgAN. Kidney pathological diagnosis (MN vs. MCD: hazard ratio [HR], 0.42; 95% confidence interval [95% CI], 0.31-0.57; IgAN vs. MCD: 0.58; 0.39-0.85), levels of 24-h urine protein at biopsy (1.04; 1.00-1.08) and presence of nodular mesangial sclerosis (0.70; 0.49-0.99) were significantly correlated with remission of proteinuria after adjusting for baseline variables. 24-h urine protein levels at biopsy (1.14; 1.04-1.25) and the presence of crescents (2.30; 1.06-4.95) were the independent risk factors for kidney disease progression events after adjusting for baseline variables. Conclusion The increasing frequency of MN was affirmed over the past two decades. The therapeutic status, clinical outcomes, and factors influencing these outcomes were presented in this single-center study for the three primary glomerular diseases. Number of China Clinical Trial Registry: ChiCTR2100043001.

3.
Food Chem ; 449: 139216, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38604031

RESUMO

This study aimed to identify saltiness-enhancing peptides from yeast protein and elucidate their mechanisms by molecular docking. Yeast protein hydrolysates with optimal saltiness-enhancing effects were prepared under conditions determined using an orthogonal test. Ten saltiness-enhancing peptide candidates were screened using an integrated virtual screening strategy. Sensory evaluation demonstrated that these peptides exhibited diverse taste characteristics (detection thresholds: 0.13-0.50 mmol/L). Peptides NKF, LGLR, WDL, NMKF, FDSL and FDGK synergistically or additively enhanced the saltiness of a 0.30% NaCl solution. Molecular docking revealed that these peptides predominantly interacted with TMC4 by hydrogen bonding, with hydrophilic amino acids from both peptides and TMC4 playing a pivotal role in their binding. Furthermore, Leu217, Gln377, Glu378, Pro474 and Cys475 were postulated as the key binding sites of TMC4. These findings establish a robust theoretical foundation for salt reduction strategies in food and provide novel insights into the potential applications of yeast proteins.

4.
Dermatol Surg ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470987

RESUMO

BACKGROUND: Facial fold and groove formation is influenced by the ptosis of the superficial fat compartments in the mid-face region. OBJECTIVE: This study aimed to design a facial rejuvenation technique that targets sagging of the mid-face fat compartments and achieves a youthful facial configuration. MATERIALS AND METHODS: A total of 102 patients underwent suture net restoration. Each specific ptosis fat compartment was carefully lifted and held at the regional facial ligaments to effectively restore volume distribution. Patient outcomes were evaluated through preoperative and postoperative photography comparison, 3-D photographic analysis, and postoperative evaluations. RESULTS: Significant mid-cheek rejuvenation was observed. The procedure resulted in a remarkable, 10.89% increase in malar projection. The nasolabial fold improved by at least 1 grade in 61.43% of the patients and by at least 2 grades in 37.14%. A total of 87.65% of the patients expressed high satisfaction or satisfaction with the outcomes of the procedure. CONCLUSION: By specifically targeting the mid-face ptosis fat compartments, the technique demonstrated significant enhancements of both the nasolabial fold and the malar projection. The results indicate that this novel technique holds promise as an efficient approach for satisfactorily addressing facial aging concerns.

5.
Food Res Int ; 181: 114078, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448095

RESUMO

The effects of α-amylase on of flavor perception were investigated via spectrum analysis, electronic tongue, on-line mass spectrometry, and molecular docking. Aroma release results showed that α-amylase exhibited variable release patterns of different aroma compounds. Electronic tongue analysis showed that the perception of bitterness, sweetness, sour, and saltiness was subtly increased and that of umami was significantly increased (p < 0.01) along with the increasing enzyme activity of α-amylase. Ultraviolet absorption and fluorescence spectroscopy analyses showed that static quenching occurred between α-amylase and eight flavor compounds and their interaction effects were spontaneous. One binding pocket was confirmed between the α-amylase and flavor compounds, and molecular docking simulation results showed that the hydrogen, electrostatic, and hydrophobic bonds were the main force interactions. The TYP82, TRP83, LEU173, HIS80, HIS122, ASP297, ASP206, and ARG344 were the key α-amylase amino acid residues that interacted with the eight flavor compounds.


Assuntos
Prótons , alfa-Amilases , Simulação de Acoplamento Molecular , Nariz Eletrônico , Espectrometria de Massas , Aminoácidos , Percepção
6.
Bioorg Chem ; 146: 107278, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484586

RESUMO

VEGFR, a receptor tyrosine kinase inhibitor (TKI), is an important regulatory factor that promotes angiogenesis and vascular permeability. It plays a significant role in processes such as tumor angiogenesis, tumor cell invasion, and metastasis. VEGFR is mainly composed of three subtypes: VEGFR-1, VEGFR-2, and VEGFR-3. Among them, VEGFR-2 is the crucial signaling receptor for VEGF, which is involved in various pathological and physiological functions. At present, VEGFR-2 is closely related to a variety of cancers, such as non-small cell lung cancer (NSCLC), Hepatocellular carcinoma, Renal cell carcinoma, breast cancer, gastric cancer, glioma, etc. Consequently, VEGFR-2 serves as a crucial target for various cancer treatments. An increasing number of VEGFR inhibitors have been discovered to treat cancer, and they have achieved tremendous success in the clinic. Nevertheless, VEGFR inhibitors often exhibit severe cytotoxicity, resistance, and limitations in indications, which weaken the clinical therapeutic effect. In recent years, many small molecule inhibitors targeting VEGFR have been identified with anti-drug resistance, lower cytotoxicity, and better affinity. Here, we provide an overview of the structure and physiological functions of VEGFR, as well as some VEGFR inhibitors currently in clinical use. Also, we summarize the in vivo and in vitro activities, selectivity, structure-activity relationship, and therapeutic or preventive use of VEGFR small molecule inhibitors reported in patents in the past three years (2021-2023), thereby presenting the prospects and insights for the future development of targeted VEGFR inhibitors.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Renais , Neoplasias Pulmonares , Humanos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química
7.
Food Res Int ; 182: 114139, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519171

RESUMO

The previously obtained chicken-derived umami peptides in the laboratory were evaluated for their saltiness-enhancing effect by sensory evaluation and S-curve, and the results revealed that peptides TPPKID, PKESEKPN, TEDWGR, LPLQDAH, NEFGYSNR, and LPLQD had significant saltiness-enhancing effects. In the binary solution system with salt, the ratio of the experimental detection threshold (129.17 mg/L) to the theoretical detection threshold (274.43 mg/L) of NEFGYSNR was 0.47, which had a synergistic saltiness-enhancing effect with salt. The model of transmembrane channel-like protein 4 (TMC4) channel protein was constructed by homology modeling, which had a 10-fold transmembrane structure and was well evaluated. Molecular docking and frontier molecular orbitals showed that the main active sites of TMC4 were Lys 471, Met 379, Cys 475, Gln 377, and Pro 380, and the main active sites of NEFGYSNR were Tyr, Ser and Asn. This study may provide a theoretical reference for low-sodium diets.


Assuntos
Galinhas , Peptídeos , Animais , Simulação de Acoplamento Molecular , Peptídeos/química , Proteínas , Cloreto de Sódio na Dieta
8.
Trials ; 25(1): 134, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383418

RESUMO

BACKGROUND: Emotional blunting is a symptom that has always been present in depressed patients. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective supplementary therapy for treating depression. However, the effectiveness and brain imaging processes of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) in the treatment of depression with emotional blunting have not been observed in randomized controlled trials. METHODS: This study is a randomized, controlled, double-blind, and single-center clinical trial in which 80 eligible depressed patients with emotional blunting will be randomly assigned to two groups: a functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) group and a control group. Individuals in the fMRI-rTMS group (n = 40) will receive high-frequency rTMS (10 Hz, 120% MT). The main target of stimulation will be the area most relevant to the functional connectivity of the right medial prefrontal cortex (mPFC) and amygdala. The control group (n = 40) will receive sham stimulation, with a coil flipped to 90 degrees relative to the vertical scalp. All patients will receive 15 consecutive days of treatment, with each session lasting half an hour per day, followed by 8 weeks of follow-up. The primary outcome is the comparison of Oxford Depression Questionnaire (ODQ) scores between these two groups at different time points. The secondary outcomes include evaluating other clinical scales and assessing the differences in brain imaging changes between the two groups before and after treatment. DISCUSSION: This trial aims to examine the effects of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) intervention on depressed patients experiencing emotional blunting and to elucidate the potential mechanism behind it. The results will provide new evidence for using fMRI-rTMS in treating depression with emotional blunting in the future. TRIAL REGISTRATION: ClinicalTrials.gov INCT05555940. Registered on 13 September 2022 at http://clinicaltrials.gov .


Assuntos
Depressão , Estimulação Magnética Transcraniana , Humanos , Encéfalo/diagnóstico por imagem , Método Duplo-Cego , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento , Depressão/terapia
9.
Cell Death Differ ; 31(4): 511-523, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38365969

RESUMO

The aberrant expression of methyltransferase Set7/9 plays a role in various diseases. However, the contribution of Set7/9 in ischemic stroke remains unclear. Here, we show ischemic injury results in a rapid elevation of Set7/9, which is accompanied by the downregulation of Sirt5, a deacetylase reported to protect against injury. Proteomic analysis identifies the decrease of chromobox homolog 1 (Cbx1) in knockdown Set7/9 neurons. Mechanistically, Set7/9 promotes the binding of Cbx1 to H3K9me2/3 and forms a transcription repressor complex at the Sirt5 promoter, ultimately repressing Sirt5 transcription. Thus, the deacetylation of Sirt5 substrate, glutaminase, which catalyzes the hydrolysis of glutamine to glutamate and ammonia, is decreased, promoting glutaminase expression and triggering excitotoxicity. Blocking Set7/9 eliminates H3K9me2/3 from the Sirt5 promoter and normalizes Sirt5 expression and Set7/9 knockout efficiently ameliorates brain ischemic injury by reducing the accumulation of ammonia and glutamate in a Sirt5-dependent manner. Collectively, the Set7/9-Sirt5 axis may be a promising epigenetic therapeutic target.


Assuntos
Isquemia Encefálica , Glutamina , Histona-Lisina N-Metiltransferase , Sirtuínas , Sirtuínas/metabolismo , Sirtuínas/genética , Animais , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Glutamina/metabolismo , Camundongos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Camundongos Endogâmicos C57BL , Masculino , Camundongos Knockout , Humanos , Regiões Promotoras Genéticas/genética , Neurônios/metabolismo
10.
Food Res Int ; 178: 113908, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309861

RESUMO

Yeast extract (YE) is derived from the soluble component in yeast cells, which is rich in peptides and has been used as a sweet-enhancing agent. It has the potential to be utilized to produce natural sweet-flavored peptides or sweet-enhancing peptides. To study the synergistic effect and mechanism of sweetness-enhancing peptides derived from YE, ultrafiltration fraction with molecular weight less than 1 kDa was screened according to sensory analysis, which showed a synergistic sweetening effect in stevioside and mogroside solution. Twenty potential taste peptides were identified from the screened fractions, among which EV, AM, AVDNIPVGPN and VDNIPVGPN showed sweetness-enhancing effects on both stevioside and mogroside. The sweetener-receptor-peptide complex was constructed to investigate the interaction of stevioside and mogroside to taste receptor type 1 member 2 accompanied by these peptides. The results of the molecular docking indicated that new hydrophobic interactions (Leu 279, Pro 308, Val 309, etc.) and hydrogen bonds (Ser 40, Ala 43, Asp 278, etc.) were formed between sweeteners and active sites in the venus flytrap domain. In conclusion, the presence of sweetness-enhancing peptides from YE improved the binding stability of sweeteners and receptors by increasing the binding interaction, especially the hydrophobic interactions, which contribute to the synergistic effect of sweetness-enhancing peptides.


Assuntos
Diterpenos do Tipo Caurano , Glucosídeos , Edulcorantes , Simulação de Acoplamento Molecular , Edulcorantes/análise , Diterpenos do Tipo Caurano/análise , Peptídeos/farmacologia
11.
Nutrients ; 16(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38337742

RESUMO

Different protein sources can impact gut microbiota composition and abundance, and also participate in health regulation. In this study, mice were gavaged with yeast protein (YP), soybean protein isolate (SPI), and whey protein isolate (WPI) for 28 days. Body weights showed similar patterns across different protein administration groups. The ileum in YP-supplemented mice exhibited good morphology, and tight-junction (TJ) proteins were slightly upregulated. Immunoglobulin (Ig)A, IgM, and IgG levels in the ileum of different protein groups were significantly increased (p < 0.05). Interleukin (IL)-10 levels were significantly increased, whereas IL-6 levels were significantly reduced in the YP group when compared with the control (C) (p < 0.05). Glutathione peroxidase (GSH-Px) levels in the ileum were significantly increased in the YP group (p < 0.05). These results indicate that YP potentially improved intestinal immunity and inflammatory profiles. The relative abundances of Parabacteroides, Prevotella, and Pseudobutyrivibrio in the YP group were more enriched when compared with the C and SPI groups, and Parabacteroides was significantly upregulated when compared with the WPI group (p < 0.05). Overall, the results indicate that YP upregulates the beneficial bacteria and improves ileal immunity and anti-inflammatory capabilities.


Assuntos
Microbioma Gastrointestinal , Animais , Camundongos , Proteínas do Soro do Leite/farmacologia , Proteínas de Soja/farmacologia , Intestinos , Proteínas Fúngicas/farmacologia
12.
Ultrason Sonochem ; 104: 106823, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38417387

RESUMO

Betanin, a water-soluble colorant, is sensitive to light and temperature and is easily faded and inactivated. This study investigated the formation of yeast protein-chitooligosaccharide-betanin complex (YCB) induced by ultrasound treatment, and evaluated its protective effect on the colorant betanin. Ultrasound (200-600 W) increased the surface hydrophobicity and solubility of yeast protein, and influenced the protein's secondary structure by decreasing the α-helix content and increasing the contents of ß-sheet and random coil. The ultrasound treatment (200 W, 15 min) facilitated binding of chitooligosaccharide and betanin to the protein, with the binding numbers of 4.26 ± 0.51 and 0.61 ± 0.06, and the binding constant of (2.73 ± 0.25) × 105 M-1 and (3.92 ± 0.10) × 104 M-1, respectively. YCB could remain the typical color of betanin, and led to a smaller and disordered granule morphology. Moreover, YCB exhibited enhanced thermal-, light-, and metal irons (ferric and copper ions) -stabilities of betanin, protected the betanin against color fading, and realized a controlled release in simulated gastrointestinal tract. This study extends the potential application of the fungal proteins for stabilizing bioactive molecules.


Assuntos
Betacianinas , Quitosana , Proteínas Fúngicas , Oligossacarídeos , Betacianinas/química , Betacianinas/farmacologia , Temperatura
13.
EMBO Rep ; 25(2): 770-795, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182816

RESUMO

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.


Assuntos
Adenina , Infecções Bacterianas , Receptor 2 Toll-Like , Animais , Camundongos , Adenina/análogos & derivados , Inflamação/genética , Metiltransferases/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
14.
Trials ; 25(1): 44, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218932

RESUMO

BACKGROUND: Anhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes in adolescents, including heightened disease severity, resistance to antidepressants, recurrence of MDD, and even suicide. Specifically, patients who suffer from anhedonia may exhibit a limited response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous researches have revealed a link between anhedonia and abnormalities within the reward circuitry, making the nucleus accumbens (NAc) a potential target for treatment. However, since the NAc is deep within the brain, repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate this specific region. Recent advances have enabled treatment technology to precisely target the left dorsolateral prefrontal cortex (DLPFC) and modify the functional connectivity (FC) between DLPFC and NAc in adolescent patients with anhedonia. Therefore, we plan to conduct a study to explore the safety and effectiveness of using resting-state functional connectivity magnetic resonance imaging (fcMRI)-guided rTMS to alleviate anhedonia in adolescents diagnosed with MDD. METHODS: The aim of this article is to provide a study protocol for a parallel-group randomized, double-blind, placebo-controlled experiment. The study will involve 88 participants who will be randomly assigned to receive either active rTMS or sham rTMS. The primary object is to measure the percentage change in the severity of anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). The assessment will be conducted from the baseline to 8-week post-treatment period. The secondary outcome includes encompassing fMRI measurements, scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Chinese Version of Temporal Experience of Pleasure Scale (CV-TEPS), and the Chinese Version of Beck Scale for Suicide Ideation (BSI-CV). The Clinical Global Impression (CGI) scores will also be taken into account, and adverse events will be monitored. These evaluations will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks. DISCUSSION: If the hypothesis of the current study is confirmed, (fcMRI)-guided rTMS could be a powerful tool to alleviate the core symptoms of MDD and provide essential data to explore the mechanism of anhedonia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05544071. Registered on 16 September 2022.


Assuntos
Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Humanos , Adolescente , Estimulação Magnética Transcraniana/efeitos adversos , Estimulação Magnética Transcraniana/métodos , Córtex Pré-Frontal Dorsolateral , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Anedonia , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Cardiovasc Pharmacol ; 83(1): 86-92, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180456

RESUMO

ABSTRACT: This study aimed to compare the cost-effectiveness of the new quadruple therapy regimen of adding sodium-glucose-linked transporter 2 (SGLT2) inhibitors, with standard treatment for patients with heart failure (HF) in China. From the payer's perspective, the dates of cardiovascular event recurrences were extracted from a meta-analysis including 6 trials, combined with the treatment cost for patients with HF in China to construct a Markov model. The outcomes included per capita medical costs and incremental cost-effectiveness ratio, using quality-adjusted life years (QALYs) data. Single-factor, probability sensitivity analysis, and scenario analysis were used to explore the potential uncertainties of the model. The per capita costs of the new quadruple therapy regimen and standard treatment were $87441.26 and $87087.54, respectively. The new regimen was associated with a mean of 21.44 QALYs gained, compared with 18.60 QALYs gained with the standard treatment. The incremental cost-effectiveness ratio was $124.03 per QALY gained. The sensitivity analysis revealed that changes in the parameters within the set range did not affect the model results. In China, compared with standard treatment, the new quadruple therapy regimen with SGLT2 inhibitors reduce the frequency of cardiovascular events among patients with HF, and it has economic advantages.


Assuntos
Análise Custo-Benefício , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , China , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/economia
16.
Transl Res ; 264: 85-96, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37879562

RESUMO

Diabetic nephropathy (DN) is one of the complications of diabetes. Long-term hyperglycemia in the kidney results in renal insufficiency, and eventually leads to end-stage renal disease. Epigenetic factor ASH2L has long been identified as a transcriptional activator, and we previously indicated that ASH2L aggravated fibrosis and inflammation in high glucose-induced glomerular mesangial cells, but the pathophysiological relevance and the mechanism of ASH2L-mediated H3K4me3 in DN is not well understood. Here we demonstrated that ASH2L is upregulated in glomeruli isolated from db/db mice. Loss of ASH2L protected glomerular injury caused by hyperglycemia, as evidenced by reduced albuminuria, preserved structure, decreased glomerular extracellular matrix deposition, and lowered renal glomerular expression of proinflammatory and profibrotic markers in db/db mice. Furthermore, we demonstrated that enrichment of ASH2L-mediated H3K4me3 on the promoter regions of ADAM17 and HIPK2 triggered their transcription, leading to aberrant activation of Notch1 signaling pathway, thereby contributing to fibrosis and inflammation in DN. The findings of this study provide compelling evidence for targeting ASH2L as a potential therapeutic strategy to prevent or slow down the progression of DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Histonas , Hiperglicemia , Animais , Camundongos , Diabetes Mellitus/patologia , Nefropatias Diabéticas/tratamento farmacológico , Fibrose , Hiperglicemia/metabolismo , Inflamação/patologia , Rim/patologia
18.
Food Chem ; 430: 136988, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37544154

RESUMO

Pea (Pisum sativum L.) protein hydrolysate (PPH) has a bitter taste, which has limited its use in food industry. γ-Glutamylation is used to debitter PPH. Results showed that the bitterness of PPH was decreased significantly due to the formation of γ-glutamyl peptides, including 16 γ-[Glu](n=1/2)-amino acids (AAs) and 8 newly discovered γ-glutamyl tripeptides (γ-Glu-Asn-Phe, γ-Glu-Leu-Val, γ-Glu-Leu-Tyr, γ-Glu-Gly-Leu, γ-Glu-Gly-Phe, γ-Glu-Gly-Tyr, γ-Glu-Val-Val, and γ-Glu-Gln-Tyr). Their total production concentrations were 27.25 µmol/L and 77.76 µmol/L, respectively. The γ-Glu-AA-AAs presented an umami-enhancing, salty-enhancing, and kokumi taste when their concentration reached 1.67 ± 0.20 âˆ¼ 2.07 ± 0.20, 1.65 ± 0.25 âˆ¼ 2.29 ± 0.45 and 0.68 ± 0.19 âˆ¼ 1.03 ± 0.22 mmol/L, respectively. The γ-Glu-AA-AAs exhibited a kokumi taste by entering the Venus flytrap (VFT) of the calcium-sensing receptor and interacting with Ser147, Ala168, and Ser170. γ-Glu-AA-AAs can enhance the umaminess of Monosodium Glutamate (MSG) as they can enter the binding pocket of the taste receptor type 1 subunit 3 (T1R3)-MSG complex.


Assuntos
Ervilhas , Paladar , Simulação por Computador , Ervilhas/química , Proteínas de Ervilha/química , Hidrolisados de Proteína/química , Modelos Moleculares , Estrutura Terciária de Proteína
19.
Foods ; 12(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38137192

RESUMO

From the preparation of bread, cheese, beer, and condiments to vegetarian meat products, fungi play a leading role in the food fermentation industry. With the shortage of global protein resources and the decrease in cultivated land, fungal protein has received much attention for its sustainability. Fungi are high in protein, rich in amino acids, low in fat, and almost cholesterol-free. These properties mean they could be used as a promising supplement for animal and plant proteins. The selection of strains and the fermentation process dominate the flavor and quality of fungal-protein-based products. In terms of function, fungal proteins exhibit better digestive properties, can regulate blood lipid and cholesterol levels, improve immunity, and promote gut health. However, consumer acceptance of fungal proteins is low due to their flavor and safety. Thus, this review puts forward prospects in terms of these issues.

20.
Clin Cosmet Investig Dermatol ; 16: 3077-3090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908409

RESUMO

Background: Facial fat compartments and their role in facial aging have gained increased recognition and are playing a significant role in facial rejuvenation. The superficial fat compartments glide inferiorly during the aging process, leading to the flattening and elongation of the face and the appearance of facial bulges, folds, and grooves. Patients and Methods: Ultrasound imaging of the facial soft tissues was performed on nine female volunteers to demonstrate the change in superficial facial fat compartments from an upright to supine position. The net suture jowl and medial cheek fat compartment repositioning technique was operated on 165 Asian patients between September 2020 and July 2021. Volume and projection change of malar and jowl regions, as well as change in elevation of malar protrusion were measured 1, 3, and 6 months postoperatively using a three-dimensional imaging system. Results: Ultrasound measurements confirmed the medial and middle cheek, nasolabial, and jowl fat compartments changed in thickness during positional changes with age-related differences. Postoperative three-dimensional imaging showed volume and projection increase in the malar region (2.23mL and 1.11mm) and decrease in the jowl region (-0.18mL and -0.52mm) by the 6-month follow-up date, and malar projection saw a superior displacement of 3.08mm. Conclusion: The superficial fat glide inferiorly within their compartments under the force of gravity and naturally reposition themselves when the effect of gravity is reversed. The net suture technique offers a minimally invasive method for lifting the jowl fat, volumizing the mid-cheek and achieving facial rejuvenation by repositioning the superficial fat compartments.

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