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1.
Chem Biodivers ; 19(1): e202100608, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34786852

RESUMO

A new globoscinic acid derivative, aspertubin A (1) along with four known compounds, were obtained from the co-culture of Aspergillus tubingensis S1120 with red ginseng. The chemical structures of compounds were characterized by using spectroscopic methods, the calculated and experimental electronic circular dichroism. Panaxytriol (2) from red ginseng, and asperic acid (4) showed significant antifeedant effect with the antifeedant rates of 75 % and 80 % at the concentrations of 50 µg/cm2 . Monomeric carviolin (3) and asperazine (5) displayed weak attractant activity on silkworm. All compounds were assayed for antifungal activities against phytopathogens A. tubingensis, Nigrospora oryzae and Phoma herbarum and the results indicated that autotoxic aspertubin A (1) and panaxytriol (2) possessed selective inhibition against A. tubingensis with MIC values at 8 µg/mL. The co-culture extract showed higher antifeedant and antifungal activities against P. herbarum than those of monoculture of A. tubingensis in ordinary medium. So the medicinal plant and endophyte showed synergistic effect on the plant disease resistance by active compounds from the coculture of A. tubingensis S1120 and red ginseng.


Assuntos
Antifúngicos/química , Aspergillus/química , Repelentes de Insetos/química , Panax/química , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Aspergillus/metabolismo , Bombyx/efeitos dos fármacos , Bombyx/crescimento & desenvolvimento , Enedi-Inos/química , Enedi-Inos/isolamento & purificação , Enedi-Inos/farmacologia , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/farmacologia , Repelentes de Insetos/isolamento & purificação , Repelentes de Insetos/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , Panax/crescimento & desenvolvimento , Panax/metabolismo , Phoma/efeitos dos fármacos , Plantas Medicinais/química , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo
2.
Bioorg Chem ; 114: 105148, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246973

RESUMO

Eight new compounds (1-8) were discovered from Trichoderma harzianum associated with edible mushroom by the one strain many compounds (OSMAC) strategy. Triharzianin A (1) is the first naturally scaffold characterized by a C13-prostaglandin skeleton. The configurations of 1-3, and 5 were determined by the Mosher's method, experimental and calculated ECD spectra, and plausible biosynthesis of stereospecific epoxidation. Most compounds indicated obvious feeding attractant activities to silkworm with attraction rates at 30-90%. Compound 7 showed anti-acetylcholinesterase (anti-AChE) activity with a ratio of 29% at a concentration of 50 µM for insecticidal potential. So 2,​3-​dialkylchromone (7) had potential of chemical entrapment and killing of insects. Compounds 2, 3 and 7-11 showed antifungal activities against Aspergillus fumigates, and Trichoderma sp. from mushroom with MICs ≤ 300 µM. The four fermentation extracts also indicated obvious feeding attractant activities to silkworm for the activities brought by active metabolites from T. harzianum. The material base of biocontrol induced by the interaction of host-fungal symbiont can be investigated by the antifungal metabolites against pathogen fungi.


Assuntos
Acetilcolinesterase/metabolismo , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Trichoderma/química , Trichoderma/efeitos dos fármacos , Animais , Antifúngicos/química , Antifúngicos/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
3.
Neuroimage ; 215: 116789, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32276063

RESUMO

BACKGROUND: This study is part of the Stroke Investigative Research and Educational Network (SIREN), the largest study of stroke patients in Africa to date, with computed tomography (CT) or magnetic resonance (MR) imaging data for each patient to confirm stroke. Prior imaging studies performed using high-field MR (≥1.5T) have shown that white matter hyperintensities (WMH), signs of microangiopathy in the subcortical brain, are correlated with many stroke risk factors as well as poor stroke outcomes. The aim of this study was the evaluation of MR images (0.3T-1.5T) from the SIREN study to determine associations between WMH volumes in West African patients and both stroke outcomes and stroke risk factors identified in the SIREN study. MATERIALS AND METHODS: Brain MR images of 130 Western African stroke patients (age â€‹= â€‹57.87 â€‹± â€‹14.22) were processed through Lesion Segmentation Toolbox of the Statistical Parametric Mapping software to extract all areas of hyperintensity in the brain. WMH was separated from stroke lesion hyperintensity and WMH volume was computed and summed. A stepwise linear regression and multivariate analysis was performed between patients' WMH volume and sociodemographic and clinical indices. RESULTS: Multivariate analysis showed that high WMH volume was statistically significantly positively correlated with age (ߠ​= â€‹0.44, p â€‹= â€‹0.001), waist/hip ratio (ߠ​= â€‹0.22, p â€‹= â€‹0.03), and platelet count (ߠ​= â€‹0.19, p â€‹= â€‹0.04) after controlling for head size in a Western African stroke population. CONCLUSION: Associations between WMH and age and waist/hip ratio previously identified in Western countries were demonstrated for the first time in a resource-limited, homogeneous black African community using low-field MR scanners.


Assuntos
Encéfalo/patologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/patologia , Substância Branca/patologia , África Ocidental/epidemiologia , Idoso , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Substância Branca/diagnóstico por imagem
4.
Alcohol Clin Exp Res ; 44(12): 2579-2587, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33201577

RESUMO

INTRODUCTION: Alcohol is among the most commonly used psychoactive drugs, yet it can produce markedly different subjective effects in different people. Certain effects, including both heightened stimulatory effects and lesser sedative effects, are thought to predict repeated or excessive use. However, we do not fully understand the nature of these individual differences or their relationships to alcohol consumption. This controlled laboratory study examined subjective and physiologic responses to a moderate dose of alcohol in social drinkers in relation to the subjects' decision to consume alcohol. METHODS: Healthy adult volunteers (N = 95) participated in a 5-session double-blind alcohol choice study. On the first 4 sessions, they received alcohol (0.8 g/kg) and placebo in alternating order, and on the fifth session, they chose and consumed whichever of the 2 they preferred. During each session, participants completed the Profile of Mood States (POMS) and Biphasic Alcohol Effects Scale (BAES) questionnaires and had their vitals recorded every 30 minutes. We compared subjective and physiologic response to alcohol during the sampling sessions in participants who chose alcohol or placebo on session 5. RESULTS: Of the 95 participants, 55 chose alcohol (choosers) and 40 chose placebo (nonchoosers). In the full sample, alcohol produced its expected effects (e.g., increased friendliness, elation, and vigor (POMS), and stimulation and sedation (BAES)). The chooser and nonchooser groups did not differ in demographic characteristics, blood alcohol levels, or cardiovascular measures. However, the choosers experienced greater alcohol-induced increases in positive mood (POMS) and liked the drug more, whereas the nonchoosers experienced greater anger, anxiety (POMS), and sedation (BAES) after alcohol. CONCLUSION: Both greater positive mood effects and lesser sedative effects after alcohol predicted preference under controlled conditions, suggesting that both factors can predict future consumption of alcohol.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Bebidas Alcoólicas , Comportamento de Escolha , Adulto , Afeto/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/epidemiologia , Bebidas Alcoólicas/estatística & dados numéricos , Pressão Sanguínea/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Testes Psicológicos , Comportamento Social , Inquéritos e Questionários , Adulto Jovem
6.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(7): 2006-10, 2016 Jul.
Artigo em Zh | MEDLINE | ID: mdl-30035513

RESUMO

In scientific research and engineering application, improving the power of fiber device is an important topic, which leads to observably rise of temperature in fiber core at the same time. In this paper, Thermal effect and its influence on absorption spectrum and lifetime of Erbium-doped fiber are studied with numerical modeling. Lorentz broadening of sub-levels is used to build the mathematical relationship between temperature and absorption spectrum. The McCumber Theory is applied to deduce the lifetime of Erbium-doped fiber in different temperature. Temperature experiments of absorption and emission spectrum from 25 to 900 ℃ are carried out, which show that the wavelength of absorption peak near 980nm increase at rate of 0.625 nm/100 ℃, the ratio of absorption peak near 1 530 nm declines at a rate of 0.001 9 dB·(m℃)-1 and the broadband of absorption spectrum near 1 530 nm increase with rising temperature. The linear variation of lifetime and peak absorption in experiment proves that the theoretical model is reasonable when the temperature is below 600 ℃.

7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(6): 1882-7, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-30052412

RESUMO

In order to promote the research on erbium-doped fiber's anti-radiation properties and fully grasp variation laws of erbium-doped fiber's properties under radiation, theoretical analysis on how irradiation effect erbium-doped Fiber based on model of color centers was conducted. The performance changes of erbium-doped fiber that may occur during irradiation were predicted. According to working principle and application characteristics, online real-time monitoring of 980 nm wave band loss spectra, 1 550 nm wave band loss spectra, luminescence spectra of two different types(EDF-L-980 and MP980) of erbium-doped fiber as well as recovery measuring after radiation were carried out,. Studies showed that spectral characteristics of both types have similar variation trends during radiation. Losses at 980 and 1 530 nm wave band increase monotonically with dose, and the relationship is approximately linear at absorption peak of 980 and 1 530 nm; luminescence spectra intensity decreases monotonically with dose, and energy of luminescence spectra is shifting to long wavelengths, while its mean wavelength and bandwidth increasing substantially. The relationship between luminescence intensity and dose is also approximately linear at luminescence peak of 1 530 nm. Erbium-doped fiber's spectral characteristics recovered modestly after radiation, but to a limited extent of less than 40% for all parameters. The experiment result is in good agreement with theoretical analysis and prediction, so rationality of theoretical explanation of erbium-doped fiber's performance changes during radiation has been proven.

8.
Int J Surg ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913430

RESUMO

OBJECTIVE: Patients with hepatocellular carcinoma (HCC) who undergo curative hepatectomy may experience varying remnant liver volumes. Our study aimed to evaluate whether the extent of liver resection has an effect on postoperative recurrence in HCC patients at China Liver Cancer Staging (CNLC) Ib stage. METHODS: A retrospective analysis was conducted on 197 patients who underwent hepatectomy for a solitary HCC lesion measuring ≥5 cm (CNLC Ιb stage) between January 2019 and June 2022. Patients were divided into major hepatectomy (MAH) group (n=70) and minor hepatectomy (MIH) group (n=127) based on the extent of liver resection. Recurrence-free survival (RFS) was compared between the two groups. Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis. RESULTS: Patients who underwent MAH had a greater total complication rate than did those who underwent MIH (35.7% vs. 11.8%, P<0.001). The median RFS was 14.6 months (95% CI: 11.1-18.1) for MAH group and 24.1 months (95% CI 21.2-27.1) for MIH group (P<0.001). After PSM, patients who underwent MAH still had a greater total complication rate than those who underwent MIH (36.7% vs. 16.3%, P=0.037). The median RFS was 13.2 months (95% CI: 15.1-21.7) for MAH group and 22.3 months (95% CI 18.1-26.5) for MIH group (P=0.0013). The Cox regression model identified MAH as an independent poor predictor for HCC recurrence (hazard ratios of 1.826 and 2.062 before and after PSM, respectively; both P<0.05). CONCLUSION: MIH can be performed with fewer postoperative complications and contributes to improved RFS in patients with HCC at CNLC Ιb stage compared to MAH. Parenchyma-sparing resection should be considered the first choice for these HCCs.

9.
Biosensors (Basel) ; 13(2)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36831976

RESUMO

The rapid diagnosis and detection of respiratory bacteria at the early stage can effectively control the epidemic spread and bacterial infection. Here, we designed a rapid, ultrasensitive, and quantitative lateral flow immunoassay (LFA) strip for simultaneous detection of respiratory bacteria S. aureus and S. pneumoniae. In this assay, the surface enhanced Raman scattering (SERS) tags were designed through combining magnetite Raman enhancement nanoparticle Fe3O4@Au/DTNB and recognition element 4-mercaptophenylboronic acid (4-MPBA). Further, 4-MPBA could capture multiple bacteria in a complex environmental solution. Based on the strategies, Fe3O4@Au/DTNB-mediated magnetic enrichment and 4-MPBA-mediated universal capture capabilities improved the detection sensitivity, the limits of detection for S. aureus and S. pneumoniae were as low as 8 and 13 CFU mL-1, respectively, which were more sensitive than those of colloidal gold method. The Fe3O4@Au/DTNB/Au/4-MPBA-LFA also exhibited good reproducibility, excellent specificity, and high recovery rates in sputum samples, indicating its potential application in the detection of respiratory bacteria samples.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus , Reprodutibilidade dos Testes , Ácido Ditionitrobenzoico , Bactérias , Fenômenos Magnéticos , Análise Espectral Raman/métodos
10.
Int J Pharm ; 637: 122877, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-36958615

RESUMO

3D printing is used in manufacturing of personalized and customized medications. Moreover, information technology has been integrated with 3D printing, which builds the basis of informative medications. Here, clonidine hydrochloride (CH) was formulated in informative wafers (info-wafers) by combination of 3D printing, code design and photopolymerization. Braille code (recognized by blind persons), bar code, and quick response (QR) code were used for the design of info-wafers. A code positive mold was 3D-printed with rigid resins by stereolithography, which was transformed to the silicone negative mold by thermal polymerization. A homogeneous CH suspension in N-vinyl pyrrolidone was casted into the negative mold followed by photopolymerization to form CH info-wafers. The bulgy parts of info-wafers were painted with edible ink except for Braille code info-wafers. The CH in info-wafers maintained the amorphous state, which was demonstrated by X-ray diffraction. The amorphous CH had rapid dissolution. Bar code info-wafers were scanned by smartphone though only simple information was obtained. QR code info-wafers were smartphone-scanned to link a website that contained sufficient information such as the instruction of CH application and the collection of patient information. Info-wafers provide online drug information and use instructions for patients to make the treatment standardization and normalization.


Assuntos
Impressão Tridimensional , Smartphone , Humanos , Estereolitografia
11.
Acta Pharm Sin B ; 13(1): 315-326, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36815028

RESUMO

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 µm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

12.
Front Cell Infect Microbiol ; 13: 1134511, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936774

RESUMO

Introduction: Inflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown. Methods: The animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction. Results and conclusions: We show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1ß levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1ß production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas Nucleares , Choque Séptico , Animais , Camundongos , Lesão Pulmonar Aguda/metabolismo , Proteínas Culina , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , SARS-CoV-2/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo
13.
J Mol Endocrinol ; 70(2)2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394986

RESUMO

Golgi protein 73 (GP73), also called Golgi membrane protein 1 (GOLM1), is a resident Golgi type II transmembrane protein and is considered as a serum marker for the detection of a variety of cancers. A recent work revealed the role of the secreted GP73 in stimulating liver glucose production and systemic glucose homeostasis. Since exaggerated hepatic glucose production plays a key role in the pathogenesis of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), GP73 may thus represent a potential therapeutic target for treating diabetic patients with pathologically elevated levels. Here, in this study, we found that the circulating GP73 levels were significantly elevated in T2DM and positively correlated with hemoglobin A1c. Notably, the aberrantly upregulated GP73 levels were indispensable for the enhanced protein kinase A signaling pathway associated with diabetes. In diet-induced obese mouse model, GP73 siRNA primarily targeting liver tissue was potently effective in alleviating abnormal glucose metabolism. Ablation of GP73 from whole animals also exerted a profound glucose-lowering effect. Importantly, neutralizing circulating GP73 improved glucose metabolism in streptozotocin (STZ) and high-fat diet/STZ-induced diabetic mice. We thus concluded that GP73 was a feasible therapeutic target for the treatment of diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/patologia , Fígado/metabolismo , Glucose/metabolismo , Homeostase
14.
Front Pharmacol ; 13: 1006299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249740

RESUMO

Extracellular vesicles are tiny lipid bilayer-enclosed membrane particles, including apoptotic bodies, micro vesicles, and exosomes. Organisms of all life forms can secrete extracellular vesicles into their surrounding environment, which serve as important communication tools between cells and between cells and the environment, and participate in a variety of physiological processes. According to new evidence, plant extracellular vesicles play an important role in the regulation of transboundary molecules with interacting organisms. In addition to carrying signaling molecules (nucleic acids, proteins, metabolic wastes, etc.) to mediate cellular communication, plant cells External vesicles themselves can also function as functional molecules in the cellular microenvironment across cell boundaries. This review introduces the source and extraction of plant extracellular vesicles, and attempts to clarify its anti-tumor mechanism by summarizing the current research on plant extracellular vesicles for disease treatment. We speculate that the continued development of plant extracellular vesicle-based therapeutic and drug delivery platforms will benefit their clinical applications.

15.
Biomater Adv ; 136: 212784, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35929299

RESUMO

An optimal wound dressing can seal variously shaped wounds and provide a complete barrier to resist bacterial invasion; more importantly, the dressing can be stretched or compressed when the wounds are subjected to external forces and quickly return to its original state after the forces are withdrawn. Here, we designed dressings with light-triggered on-site rapid formation of antibacterial hydrogel for the accelerated healing of infected wounds. The pro-hydrogel, composed of acrylamide (AM) and dopamine-hyaluronic acid-ε-poly-l-lysine (DA-HA-EPL), was filled into the Vibrio vulnificus-infected wound. A 405-nm blue light was exerted on the wound to rapidly photopolymerize AM to its polymer, i.e., polyacrylamide (PAM). A hydrogel network of PAM/DA-HA-EPL immediately formed on site within several seconds to insulate the wound. PAM/DA-HA-EPL possessed adhesion performance to adapt to changes in wound morphologies due to external forces. Moreover, it presented high antibacterial ability due to the presence of EPL, in vitro biocompatibility and the ability to promote cell migration. Vibrio vulnificus-infected wounds were established on full-thickness mouse skin, and the hydrogel dressing exhibited high healing efficiency in terms of skin tissue regeneration, collagen deposition, and angiogenesis. PAM/DA-HA-EPL is a promising hydrogel dressing for the accelerated healing of infected wounds.


Assuntos
Hidrogéis , Infecção dos Ferimentos , Animais , Antibacterianos/farmacologia , Bandagens , Camundongos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
16.
Front Oncol ; 12: 835603, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35965501

RESUMO

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy.

17.
Nat Metab ; 4(1): 29-43, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34992299

RESUMO

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.


Assuntos
COVID-19/complicações , COVID-19/virologia , Glucose/metabolismo , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Proteínas de Membrana/metabolismo , SARS-CoV-2 , Animais , Biomarcadores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Jejum , Expressão Gênica , Gluconeogênese/efeitos dos fármacos , Gluconeogênese/genética , Interações Hospedeiro-Patógeno , Humanos , Hiperglicemia/sangue , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Especificidade de Órgãos/genética
18.
Pharmacol Biochem Behav ; 204: 173158, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675838

RESUMO

BACKGROUND: It is commonly believed that drugs, including stimulants, are used recreationally because of their ability to induce pleasurable subjective effects. However, recreational drug use sometimes occurs in the absence of positive subjective effects, suggesting that other factors contribute. Here, we examine the extent to which the direct subjective effects of amphetamine, a commonly misused stimulant, predict subsequent choice of the drug vs placebo. METHODS: Healthy adults (N = 112) participated in a five-session amphetamine choice study. On the first four sessions, participants sampled either 20 mg d-amphetamine or placebo in color-coded capsules two times each. On the fifth session, they chose which color (d-amphetamine or placebo) they preferred. We examined the choice of drug vs placebo in relation to demographic characteristics, baseline mood states, personality and subjective and cardiovascular responses to acute administration of the drug. RESULTS: Eighty-one participants chose amphetamine (Choosers) while 31 chose placebo (Non-choosers). Overall, amphetamine produced typical stimulant-like effects on subjective questionnaires, and it elevated heart rate and blood pressure vs placebo. Choosers reported greater positive mood, elation and stimulant-like effects following amphetamine compared to Non-choosers. The Choosers also exhibited a greater increase in systolic blood pressure, but not heart rate. The groups did not differ on demographic characteristics, mood states before drug administration or personality. CONCLUSIONS: These findings support the idea that pleasurable subjective responses to amphetamine, including positive mood, elation, and stimulant-like effects influence behavioral choice of the drug.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Comportamento de Escolha/efeitos dos fármacos , Dextroanfetamina/administração & dosagem , Adulto , Afeto/efeitos dos fármacos , Nível de Alerta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Dextroanfetamina/farmacologia , Feminino , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Personalidade/efeitos dos fármacos , Uso Recreativo de Drogas , Adulto Jovem
19.
ACS Omega ; 6(11): 7275-7285, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33778242

RESUMO

A series of trace compounds (diamondoids, ethanodiamondoids, and thiadiamondoids) were detected through two-dimensional gas chromatography/time-of-flight mass spectrometry (GC × GC-TOFMS) analysis of Ordovician condensate samples from the Tazhong area. Gas chromatography-mass spectrometry (GC-MS) analysis showed that the biomarker parameters are less effective for high-maturity oils. Carbon isotope and geochemical features suggested that the gas is a high-temperature cracking gas when its temperature is higher than 170 °C. The H2S content is 8.27%, suggesting that it is affected by thermochemical sulfate reduction (TSR). However, the geological analysis indicated that the Ordovician reservoirs do not satisfy the conditions for TSR. The high-maturity oil in the Ordovician reservoirs may generate diamondoids and ethanodiamondoids when cracking, while TSR and severe cracking occur in deep Cambrian source rocks and produce a large number of diamondoids, ethanodiamondoids, organic sulfur compounds (OSCs), etc. The secondary geochemical products that are carried up by the dry gas and migrate upward through faults and are enriched in Ordovician crude oil reservoirs. On this basis, we proposed that the condensate presented was formed by the mixing of dry gas from Cambrian oil that was altered by cracking and TSR into Ordovician in situ slightly cracked oil, therefore speculating that the favorable reservoir-seal assemblages in this area may contain abundant oil and gas resources. Consequently, improved knowledge of secondary alteration effects on the reservoir and underground fluids is vital for oil and gas prediction and exploration development in the next step.

20.
Pharmaceutics ; 13(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918471

RESUMO

Jojoba (Simmondsia chinensis (Link) C.K. Schneid) is a dioecious plant in desert and semi-desert areas, e.g., the Ismailia Desert in Egypt. Jojoba oil (JJBO) is a natural slight yellow oil with the functions of skin barrier repairing and wound healing, which is dermally applied as a traditional medication or cosmetic in the Middle East. The objective of this study was to prepare JJBO dry nanoemulsion powders (JNDs) and investigate their anti-acute lung injury effects. JJBO nanoemulsions (JNEs) were prepared and then lyophilized to JNDs and the properties and simulated lung deposition were measured. Rat acute lung injury (ALI) models were established after intratracheal (i.t.) administration of lipopolysaccharide (LPS) or hydrogen peroxide (H2O2). JNDs and dexamethasone (DXM) solutions were also i.t. administered to the rats. The pathological states of lung tissues were checked. Inflammatory and oxidative factors in the lung tissues were determined using ELISA methods. NF-κB p65 and caspase-3 were measured with a Western blotting method and an immunohistochemical method, respectively. JNDs had an appropriate mass median aerodynamic diameter (MMAD) of 4.17 µm and a fine particle fraction (FPF) of 39.11%. JNDs showed higher anti-inflammatory effect on LPS-induced ALI than DXM with a decrease in total protein content and down-regulation of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and NF-κB p65. JNDs also showed higher anti-inflammatory and anti-oxidation effect on H2O2-induced ALI than DXM with elimination of reactive oxygen species (ROS), increasing of superoxide dismutase (SOD), decrease in of lipid peroxide malondialdehyde (MDA) and glutathione (GSH), and inhibition of caspase-3 expression. Moreover, i.t. JNDs attenuated bleeding and infiltrations of the inflammatory cells in the two ALI models. JNDs are a promising natural oil-contained inhalable medication for the treatment of LPS- or H2O2-induced ALI.

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