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1.
Langmuir ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739034

RESUMO

Band 3, or anion exchanger 1 (AE1), is one of the indispensable transmembrane proteins involved in the effective respiratory process of the human body and is primarily responsible for the exchange of bicarbonate and chloride anions across the plasma membrane of erythrocyte. However, the molecular mechanism of ion transport of Band 3 is not completely understood, yet. In this work, we systematically investigate the key binding sites of bicarbonate ions in Band 3 and the impact of cholesterol (CHOL) in lipid bilayers on bicarbonate ion binding using all-atom molecular dynamics (MD) simulations. We examine the dynamics of interactions of bicarbonate ions with Band 3 in the microsecond time scale and calculate the binding free energy of the anion in Band 3. The results indicate that the residue R730 of Band 3 is the most probable binding site for bicarbonate ions. CHOL enhances the bicarbonate ion binding by influencing the conformational stability of Band 3 and compressing the volume of the Band 3 cavity. These findings provide some insights into the bicarbonate ion binding in Band 3 and are helpful for understanding the anion exchange of Band 3.

2.
Drug Des Devel Ther ; 18: 1627-1650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774483

RESUMO

With ever-increasing intensive studies of idiopathic pulmonary fibrosis (IPF), significant progresses have been made. Endoplasmic reticulum stress (ERS)/unfolded protein reaction (UPR) is associated with the development and progression of IPF, and targeting ERS/UPR may be beneficial in the treatment of IPF. Natural product is a tremendous source of new drug discovery, and accumulating studies have reported that many natural products show potential therapeutic effects for IPF via modulating one or more branches of the ERS signaling pathway. Therefore, this review focuses on critical roles of ERS in IPF development, and summarizes herbal preparations and bioactive compounds which protect against IPF through regulating ERS.


Assuntos
Produtos Biológicos , Estresse do Retículo Endoplasmático , Fibrose Pulmonar Idiopática , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Animais , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
3.
Immunol Cell Biol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710590

RESUMO

The γδ T cells are a subpopulation of T cells that are abundantly found in the skin and mucous membranes. Their reactivity to self-antigens and ability to secrete various cytokines make them a key component in psoriasis development. Although the correlation between the immune repertoire (IR) of γδ T-cell receptors and the occurrence and severity of psoriasis remains incompletely explored, high-throughput sequencing of γδ T cells has led to a deeper understanding of IR in psoriasis. This study investigated the differences between γδ T cells in patients with psoriasis and healthy controls. The γδ T cells were identified via immunofluorescence staining and a correlation analysis was performed according to the psoriasis area and severity index (PASI) scores. The IR sequencing method was used to detect IR in the γδ T-cell receptors. The findings demonstrated more skin γδ T cells in patients with psoriasis, which were positively correlated with the PASI score. There were subtle differences in most variable (V), diversity (D) and joining (J) gene segments and VJ/VDJ combination segments between patients with psoriasis and healthy controls. However, a higher diversity of complementarity-determining region 3 (CDR3) was observed in patients with psoriasis. In summary, the IR of skin γδ T cells was significantly altered in patients with psoriasis, and the diversity in the cell's CDR3 population is a promising biomarker for assessment of psoriasis severity.

4.
Angew Chem Int Ed Engl ; : e202405592, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647330

RESUMO

In aqueous aluminum-ion batteries(AAIBs), the insertion/extraction chemistry of Al3+ often leads to poor kinetics, whereas the rapid diffusion kinetics of hydrated hydrogen ions (H3O+) may offer the solution. However, the presence of considerable Al3+ in the electrolyte hinders the insertion reaction of H3O+. Herein, we report how oxygen-deficient α-MoO3 nanosheets unlock selective H3O+ insertion in a mild aluminum-ion electrolyte. The abundant oxygen defects impede the insertion of Al3+ due to excessively strong adsorption, while allowing H3O+ to be inserted/diffused through the Grotthuss proton conduction mechanism. This research advances our understanding of the mechanism behind selective H3O+ insertion in mild electrolytes.

5.
J Chem Theory Comput ; 20(9): 4045-4053, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38648670

RESUMO

pH-responsive nanoparticles are ideal vehicles for drug delivery and are widely used in cell imaging in targeted therapy of cancer, which usually has a weakly acidic microenvironment. In this work, we constructed a titratable molecular model for nanoparticles grafted with ligands of pH-sensitive carboxylic acids and investigated the interactions between the nanoparticles and the lipid bilayer in varying pH environments. We mainly examined the effect of the grafting density of the pH-sensitive ligands of the nanoparticles on the interactions of the nanoparticles with the lipid bilayer. The results show that the nanoparticles can penetrate the lipid bilayer only when the pH value is lower than a critical value, which can be readily modulated to the specific pH value of the tumor microenvironment by changing the ligand grafting density. This work provides some insights into modulating the interactions between the pH-sensitive nanoparticles and cellular membranes to realize targeted drug delivery to tumors based on their specific pH environment.


Assuntos
Bicamadas Lipídicas , Nanopartículas , Bicamadas Lipídicas/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Humanos , Simulação de Dinâmica Molecular , Ácidos Carboxílicos/química , Ligantes , Microambiente Tumoral
6.
Clin Toxicol (Phila) ; : 1-8, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668745

RESUMO

INTRODUCTION: Many studies have focused on snakebites in adults, but very few have described snakebites in children. METHODS: We reviewed the clinical characteristics and outcomes of children with venomous snakebites aged less than 15 years who presented to a regional medical centre in South China from January 2013 to December 2022. RESULTS: A total of 69 envenomed patients were analyzed in our study; 42 (60.9 per cent) patients were male, and 59 (85.5 per cent) reported lower limb bites. Most bites (89.8 per cent) occurred between April and October. Twenty-seven patients received first aid management, and 47 required admission to the general ward. Antivenom was administered to 58 patients, glucocorticoids to 43 patients, antibiotics to 48 patients, and tetanus antitoxin to 40 patients. No fatalities were reported. The most common snake identified was Trimeresurus albolabris. Four were classified as dry bites, 15 as mild, 43 as moderate, and seven as severe. The most common local signs were pain and swelling, while the most common systemic effects were haematological complications. Patients with high severity scores had significantly higher lactate dehydrogenase activities, creatine kinase isoenzyme activities, aspartate aminotransferase activities, D-dimer concentrations, prothrombin times and lower fibrinogen concentrations. In a receiver operating characteristic curve analysis of the values with the highest Youden index, the following cut-offs proved significant: lactate dehydrogenase activity > 248.1 U/L, creatine kinase isoenzyme activities > 17.5 U/L, fibrinogen concentration < 1,455 mg/L, D-dimer concentration > 437.0 µg/L, aspartate aminotransferase activity > 26.1 U/L, and prothrombin time > 15.2 seconds. DISCUSSION: This study provides insight into the epidemiology, clinical profile, and management of snakebites in children. Data from the present study were compared with those from our previous adult study. Limitations include that 50.7 per cent of our snakebites were attributed to Trimeresurus albolabris. Therefore, the results of our study may not be generalizable to all snakebites. CONCLUSION: The clinical symptoms were more severe in children than in adults in our previous study. Even though there were no fatalities, close monitoring should be performed to detect haematological and other potentially fatal complications promptly.

7.
Metabolites ; 14(4)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38668352

RESUMO

Temperature is vital in plant growth and agricultural fruit production. Litchi chinensis Sonn, commonly known as litchi, is appreciated for its delicious fruit and fragrant blossoms and is susceptible to stress when exposed to low temperatures. This study investigates the effect of two cryoprotectants that counteract cold stress during litchi flowering, identifies the genes that generate the cold resistance induced by the treatments, and hypothesizes the roles of these genes in cold resistance. Whole plants were treated with Bihu and Liangli cryoprotectant solutions to protect inflorescences below 10 °C. The soluble protein, sugar, fructose, sucrose, glucose, and proline contents were measured during inflorescence. Sucrose synthetase, sucrose phosphate synthetase, antioxidant enzymes (SOD, POD, CAT), and MDA were also monitored throughout the flowering stage. Differentially expressed genes (DEGs), gene ontology, and associated KEGG pathways in the transcriptomics study were investigated. There were 1243 DEGs expressed after Bihu treatment and 1340 in the control samples. Signal transduction pathways were associated with 39 genes in the control group and 43 genes in the Bihu treatment group. The discovery of these genes may contribute to further research on cold resistance mechanisms in litchi. The Bihu treatment was related to 422 low-temperature-sensitive differentially accumulated metabolites (DAMs), as opposed to 408 DAMs in the control, mostly associated with lipid metabolism, organic oxidants, and alcohols. Among them, the most significant differentially accumulated metabolites were involved in pathways such as ß-alanine metabolism, polycyclic aromatic hydrocarbon biosynthesis, linoleic acid metabolism, and histidine metabolism. These results showed that Bihu treatment could potentially promote these favorable traits and increase fruit productivity compared to the Liangli and control treatments. More genomic research into cold stress is needed to support the findings of this study.

8.
J Hematol Oncol ; 17(1): 15, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539271

RESUMO

The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo. The top-performing TCR was further tested for its affinity and cytotoxic effect against SARS-CoV-2-associated epitopes. Furthermore, single-cell RNA sequencing (scRNA-seq), immune repertoire sequencing (IR-seq) and flow cytometry were used to access vaccine-induced cellular immunity, which demonstrated that robust T cell responses (T cell activation, tissue-resident memory T cell (Trm) generation, and TCR clonal expansion) could be induced by intranasal vaccination. In summary, we identified the SARS-CoV-2-associated TCR repertoires profile, specific TCRs and T cell responses. This study provides a theoretical basis for developing effective immunization strategies.


Assuntos
COVID-19 , Vacinas , Humanos , Linfócitos T , SARS-CoV-2 , Receptores de Antígenos de Linfócitos T
9.
Environ Pollut ; 348: 123828, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38522604

RESUMO

Glyphosate (GLY) is a widely used herbicide that has been revealed to inhibit testosterone synthesis in humans and animals. Melatonin (MET) is an endogenous hormone that has been demonstrated to promote mammalian testosterone synthesis via protecting mitochondrial function. However, it remains unclear whether MET targets mitochondria to alleviate GLY-inhibited testosterone synthesis in avian. In this study, an avian model using 7-day-old rooster upon chronic exposure to GLY with the treatment of MET was designed to clarify this issue. Data first showed that GLY-induced testicular Leydig cell damage, structural damage of the seminiferous tubule, and sperm quality decrease were mitigated by MET. Transcriptomic analyses of the testicular tissues revealed the potentially critical role of mitophagy and steroid hormone biosynthesis in the process of MET counteracting GLY-induced testicular damage. Also, validation data demonstrated that the inhibition of testosterone synthesis due to GLY-induced mitochondrial dynamic imbalance and concomitant Parkin-dependent mitophagy activation is alleviated by MET. Moreover, GLY-induced oxidative stress in serum and testicular tissue were significantly reversed by MET. In summary, these findings demonstrate that MET effectively ameliorates GLY-inhibited testosterone synthesis by inhibiting mitophagy activation, which provides a promising remedy for the application of MET as a potential therapeutic agent to antagonize reproductive toxicity induced by GLY and similar contaminants.


Assuntos
Glifosato , Melatonina , Humanos , Masculino , Animais , Testosterona , Melatonina/farmacologia , Galinhas , Sêmen , Mitocôndrias , Mamíferos
10.
Liver Int ; 44(6): 1435-1447, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38483145

RESUMO

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).


Assuntos
Fígado , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Fígado/patologia , Fígado/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Resultado do Tratamento , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Recidiva , Idoso , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Esquema de Medicação
11.
Proc Natl Acad Sci U S A ; 121(12): e2318716121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38483991

RESUMO

Deep convection in the Asian summer monsoon is a significant transport process for lifting pollutants from the planetary boundary layer to the tropopause level. This process enables efficient injection into the stratosphere of reactive species such as chlorinated very-short-lived substances (Cl-VSLSs) that deplete ozone. Past studies of convective transport associated with the Asian summer monsoon have focused mostly on the south Asian summer monsoon. Airborne observations reported in this work identify the East Asian summer monsoon convection as an effective transport pathway that carried record-breaking levels of ozone-depleting Cl-VSLSs (mean organic chlorine from these VSLSs ~500 ppt) to the base of the stratosphere. These unique observations show total organic chlorine from VSLSs in the lower stratosphere over the Asian monsoon tropopause to be more than twice that previously reported over the tropical tropopause. Considering the recently observed increase in Cl-VSLS emissions and the ongoing strengthening of the East Asian summer monsoon under global warming, our results highlight that a reevaluation of the contribution of Cl-VSLS injection via the Asian monsoon to the total stratospheric chlorine budget is warranted.

12.
Sci Bull (Beijing) ; 69(8): 1091-1099, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38395650

RESUMO

Controlling the atomic arrangement of elemental atoms in intermetallic catalysts to govern their surface and subsurface properties is a crucial but challenging endeavor in electrocatalytic reactions. In hydrogen evolution reaction (HER), adjusting the d-band center of the conventional noble-metallic Pt by introducing Fe enables the optimization of catalytic performance. However, a notable gap exists in research on the effective transition from disordered Fe/Pt alloys to highly ordered intermetallic compounds (IMCs) such as FePt3 in the alkaline HER, hampering their broader application. In this study, a series of catalysts FePt3-xH (x = 5, 6, 7, 8 and 9) supported on carbon nanotubes (CNTs) were synthesized via a simple impregnation method, along with a range of heat treatment processes, including annealing in a reductive atmosphere, to regulate the order degree of the arrangement of Fe/Pt atoms within the FePt3 catalyst. By using advanced microscopy and spectroscopy techniques, we systematically explored the impact of the order degree of FePt3 in the HER. The as-prepared FePt3-8H exhibited notable HER catalytic activity with low overpotentials (η = 37 mV in 1.0 mol L-1 KOH) at j = 10 mA cm-2. The surface of the L12 FePt3-8H catalyst was demonstrated to be Pt-rich. The Pt on the surface was not easily oxidized due to the unique Fe/Pt coordination, resulting in significant enhancement of HER performance.

13.
Gene ; 908: 148278, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38360121

RESUMO

Eucommia ulmoides (E. ulmoides) is widely cultivated and exhibits remarkable adaptability in China. It is the most promising rubber source plant in the temperate zone. E. ulmoides gum (EUG) is a trans-polyisoprene with a unique "rubber-plastic duality", and is widely used in advanced materials and biomedical fields. The transcription of Farnesyl pyrophosphate synthase (FPS), the rate-limiting enzyme of EUG biosynthesis, is controlled by regulatory mechanisms that remain poorly elucidated. In this research, 12 TGA transcription factors (TFs) in E. ulmoides were identified. Promoter prediction results revealed that the EuFPS1 promoter had binding sites for EuTGAs. Subsequently, the EuTGA1 was obtained by screening the E. ulmoides cDNA library using the EuFPS1 promoter as a bait. The individual yeast one­hybrid and dual-luciferase assays confirmed that in the tobacco plant, EuTGA1 interacted with the EuFPS1 promoter, resulting in a more than threefold increase in the activity of the EuFPS1. Subcellular localization study further revealed that EuTGA1 is localized in the nucleus and acts as a TF to regulate EuFPS1 expression. In addition, qRT-PCR analysis demonstrated that the expression trend of EuFPS1 and EuTGA1 was the same at different time of the year. Notably, low temperature and MeJA treatments down-regulated EuTGA1 expression. Additionally, the transient transformation of EuTGA1 enhanced NtFPS1 expression in tobacco plants. Overall, this study identified a TF that interacted with EuFPS1 promoter to positively regulate EuFPS1 expression. The findings of this study provide a theoretical basis for further research on the expression regulation of EuFPS1.


Assuntos
Eucommiaceae , Borracha , Borracha/metabolismo , Eucommiaceae/genética , Eucommiaceae/química , Eucommiaceae/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Biblioteca Gênica , Geraniltranstransferase/genética
14.
Chin J Integr Med ; 30(3): 195-202, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374490

RESUMO

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Plantas Medicinais , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Banhos , Método Duplo-Cego , Extratos Vegetais/uso terapêutico
15.
PLoS One ; 19(2): e0289300, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306334

RESUMO

Nitrous oxide (N2O) and ammonia (NH3) volatilization (AV) are the major pathways of nitrogen (N) loss in soil, and recently, N2O and NH3 mitigation has become urgently needed in agricultural systems worldwide. However, the influence of straw incorporation (SI) and biochar addition (BC) on N2O and NH3 emissions are still unclear. To fill this knowledge gap, a soil column experiment was conducted with two management strategies using straw - straw incorporation (S1) and straw removal (S0) - and four biochar application rates (0 (C0), 15 (C1), 30 (C2), and 45 t ha-1 (C3)) to evaluate the impacts of their interactions on N2O and NH3 emissions. The results showed that NO3--N concentration and pH was the major contributors to affect the N2O and NH3 losses. Without biochar addition, N2O emissions was decreased by 59.6% (P<0.05) but AV was increased by 97.3% (P<0.05) under SI when compared to SR. Biochar was beneficial for N2O mitigation when straw was removed, but increased N2O emission by 39.4%-83.8% when straw was incorporated. Additionally, biochar stimulated AV by 27.9%-60.4% under S0 and 78.6%-170.3% under S1. Consequently, SI was found to significantly interact with BC in terms of affecting N2O (P<0.001) and NH3 (P<0.001) emissions; co-application of SI and BC promoted N2O emissions and offset the mitigation potential by SI or BC alone. The indirect N2O emissions caused by AV, however, might offset the reduction of direct N2O caused by SI or BC, thus leading to an increase in overall N2O emission. This paper recommended that SI combined BC at the amount of 8.2 t ha-1 for maintaining a lower overall N2O emission for future agriculture practices, but the long-term impacts of straw incorporation and biochar addition on the trade-off between N2O and NH3 emissions and reactive N losses should be further examined and assessed.


Assuntos
Óxido Nitroso , Solo , Óxido Nitroso/análise , Fertilizantes/análise , Agricultura/métodos , Carvão Vegetal
16.
Antioxidants (Basel) ; 13(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38397780

RESUMO

Ferroptosis, as a novel regulable cell death, is characterized by iron overload, glutathione depletion, and an accumulation of lipid peroxides. Recently, it has been discovered that ferroptosis is involved in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and plays a crucial role in renal tubular cell death. In this study, we tried to investigate the effect and mechanism of liproxstatin-1 (Lip-1) in I/R-induced AKI and seek the key regulator of ferroptosis in I/R-induced AKI. Mice were administrated with clamping bilateral renal pedicles for 30 min. We found that early growth response 1 (EGR1) might be a key regulator of ferroptosis, and Lip-1 could suppress ferroptosis via EGR1. Meanwhile, Lip-1 could reduce macrophage recruitment and the release of inflammatory cytokines. These findings indicated that Lip-1 alleviated I/R-induced AKI via regulating EGR1, and it might pave the theoretical basis of a new therapeutic strategy for I/R-induced AKI.

17.
J Ethnopharmacol ; 323: 117647, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38163558

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. AIM OF THE STUDY: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. MATERIALS AND METHODS: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg-1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg-1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. RESULTS: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. CONCLUSIONS: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.


Assuntos
Diabetes Mellitus Experimental , Medicamentos de Ervas Chinesas , Animais , Camundongos , Fator 2 Relacionado a NF-E2 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Cromatografia Líquida , Diabetes Mellitus Experimental/tratamento farmacológico , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Fígado , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
18.
Front Biosci (Landmark Ed) ; 29(1): 37, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38287823

RESUMO

Human health is seriously endangered by spontaneous intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). Because the majority of ICH and aSAH survivors experience disability, increased risk of stroke recurrence, cognitive decline, and systemic vascular disease, ICH and aSAH assume special importance in neurological disease. Early detection and prediction of neurological function and understanding of etiology and correction are the basis of successful treatment. ICH and aSAH cause complex inflammatory cascades in the brain. In order to establish precise staging and prognosis, as well as provide a basis for treatment selection and monitoring, it is imperative to determine appropriate biological markers according to pathological and physiological mechanisms. In this review, we focus on the research progress of S100B, an endogenous danger signaling molecule, as a potential biomarker for ICH and aSAH, assisting in the development of further basic research and clinical translational studies.


Assuntos
Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Hemorragia Cerebral , Fatores de Risco , Biomarcadores , Subunidade beta da Proteína Ligante de Cálcio S100
20.
Small ; 20(8): e2305607, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37817357

RESUMO

The molecule-electrode coupling plays an essential role in photoresponsive devices with photochromic molecules, and the strong coupling between the molecule and the conventional electrodes leads to/ the quenching effect and limits the reversibility of molecular photoswitches. In this work, we developed a strategy of using transition metal dichalcogenides (TMDCs) electrodes to fabricate the thiol azobenzene (TAB) self-assembled monolayers (SAMs) junctions with the eutectic gallium-indium (EGaIn) technique. The current-voltage characteristics of the EGaIn/GaOx //TAB/TMDCs photoswitches showed an almost 100% reversible photoswitching behavior, which increased by ∼28% compared to EGaIn/GaOx //TAB/AuTS photoswitches. Density functional theory (DFT) calculations showed the coupling strength of the TAB-TMDCs electrode decreased by 42% compared to that of the TAB-AuTS electrode, giving rise to improved reversibility. our work demonstrated the feasibility of 2D TMDCs for fabricating SAMs-based photoswitches with unprecedentedly high reversibility.

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