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1.
Vet Res ; 55(1): 42, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575961

RESUMO

African Swine Fever virus (ASFV), the causative agent of African swine fever, is a highly lethal hemorrhagic virus affecting domestic pigs and wild boars. The primary target cells for ASFV infection are porcine alveolar macrophages (PAMs), which are difficult to obtain and maintain in vitro, and less subjective to genetic editing. To overcome these issues and facilitate ASFV research, we obtained a subclonal cell line PK1-C5 by subcloning LLC-PK1 cells that support stable ASFV proliferation. This consequential cell line exhibited high ASFV infection levels and similar viral growth characteristics to PAMs, while also allowing high-efficiency genomic editing through transfection or lentivirus transduction of Cas9. Taken together, our study provided a valuable tool for research aspects including ASFV-host interactions, pathogenicity, and vaccine development.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Doenças dos Suínos , Suínos , Animais , Vírus da Febre Suína Africana/genética , Sus scrofa , Linhagem Celular , Rim
2.
Ying Yong Sheng Tai Xue Bao ; 35(3): 587-596, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646745

RESUMO

To investigate the longitudinal variation patterns of sapwood, heartwood, bark and stem moisture content along the trunk of artificial Larix olgensis, we constructed mixed effect models of moisture content based on beta regression by combining the effects of sampling plot and sample trees. We used two sampling schemes to calibrate the model, without limiting the relative height (Scheme Ⅰ) and with a limiting height of less than 2 m (Scheme II). The results showed that sapwood and stem moisture content increased gradually along the trunk, heartwood moisture content decreased slightly and then increased along the trunk, and bark moisture content increased along the trunk and then levelled off before increasing. Relative height, height to crown base, stand area at breast height per hectare, age, and stand dominant height were main factors driving moisture content of L. olgensis. Scheme Ⅰ showed the stable prediction accuracy when randomly sampling moisture content measurements from 2-3 discs to calibrate the model, with the mean absolute percentage error (MAPE) of up to 7.2% for stem moisture content (randomly selected 2 discs), and the MAPE of up to 7.4%, 10.5% and 10.5% for sapwood, heartwood and bark moisture content (randomly selected 3 discs), respectively. Scheme Ⅱ was appropriate when sampling moisture content measurements from discs of 1.3 and 2 m height and the MAPE of sapwood, heartwood, bark and stem moisture content reached 7.8%, 11.0%, 10.4% and 7.1%, respectively. The prediction accuracies of all mixed effect beta regression models were better than the base model. The two-level mixed effect beta regression models, considering both plot effect and tree effect, would be suitable for predicting moisture content of each part of L. olgensis well.


Assuntos
Larix , Caules de Planta , Água , Larix/crescimento & desenvolvimento , Larix/química , Caules de Planta/química , Caules de Planta/crescimento & desenvolvimento , Água/análise , Água/química , Análise de Regressão , Madeira/química , Modelos Teóricos , Previsões
3.
Sci Rep ; 14(1): 9220, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649697

RESUMO

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

4.
BMC Microbiol ; 24(1): 98, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528458

RESUMO

OBJECTIVE: The association between heart failure (HF) and intestinal inflammation caused by a disturbed intestinal microbiota in infants with congenital heart disease (CHD) was investigated. METHODS: Twenty infants with HF and CHD who were admitted to our hospital between October 2021 and March 2022 were included in this study. Twenty age- and sex-matched infants without HF at our hospital were selected as the control group. Faecal samples were obtained from each participant and analysed by enzyme-linked immunoassay and 16 S rDNA sequencing to assess intestinal inflammatory factors and the microbiota. RESULTS: The levels of intestinal inflammatory factors, including IL-1ß, IL-4, IL-6, IL-17 A and TNF-α, were greatly increased, while the levels of IL-10 were significantly decreased in the HF group compared to the control group (p < 0.05). The intestinal microbial diversity of patients in the HF group was markedly lower than that in the control group (p < 0.05). The abundance of Enterococcus was significantly increased in the HF group compared to the control group (p < 0.05), but the abundance of Bifidobacterium was significantly decreased in the HF group compared to the control group (p < 0.05). The diversity of the intestinal microbiota was negatively correlated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was positively correlated with that of IL-10. The abundance of Enterococcus was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was negatively correlated with that of IL-10. NT-proBNP was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. The heart function score was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. CONCLUSIONS: Infants with CHD-related HF had a disordered intestinal microbiota, decreased diversity of intestinal microbes, increased levels of pathogenic bacteria and decreased levels of beneficial bacteria. The increased abundance of Enterococcus and the significant decrease in the diversity of the intestinal microbiota may exacerbate the intestinal inflammatory response, which may be associated with the progression of HF.


Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Lactente , Humanos , Interleucina-10 , Fator de Necrose Tumoral alfa , Interleucina-6 , Interleucina-4 , Insuficiência Cardíaca/complicações , Cardiopatias Congênitas/complicações , Enterococcus/genética , Inflamação
5.
Mar Drugs ; 22(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38535469

RESUMO

Chitosan oligosaccharides are the degradation products of chitin obtained from the shell extracts of shrimps and crabs. Compared with chitosan, chitosan oligosaccharides have better solubility and a wider application range. In this study, high-molecular-weight chitosan oligosaccharides (COST, chitosan oligosaccharides, MW ≤ 1000) were isolated and purified by a GPC gel column, and the molecular weight range was further reduced to obtain high-purity and low-molecular-weight chitosan (COS46). Compared with COST, COS46 is better at inhibiting CCl4-induced cell death, improving cell morphology, reducing ALT content, and improving cell antioxidant capacity. The effects of COST and COS46 on CCl4-induced acute liver injury were further verified in mice. Both COS46 and COST improved the appearance of the liver induced by CCl4, decreased the levels of ALT and AST in serum, and decreased the oxidation/antioxidant index in the liver. From the liver pathological section, the effect of COS46 was better. In addition, some indicators of COS46 showed a dose-dependent effect. In conclusion, compared with COST, low-molecular-weight COS46 has better antioxidant capacity and a better therapeutic effect on CCl4-induced acute liver injury.


Assuntos
Quitosana , Animais , Camundongos , Antioxidantes , Fígado , Morte Celular , Oligossacarídeos
6.
Transl Pediatr ; 13(2): 260-270, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38455752

RESUMO

Background: Timely and accurate pathogen diagnosis can be challenging in children who contract a respiratory virus following congenital heart surgery (CHS). This often results in suboptimal drug use and treatment delays. Metagenomics next-generation sequencing (mNGS) is a swift, efficient, and unbiased method for obtaining microbial nucleic acid sequences. This technology holds promise as a comprehensive diagnostic tool, especially for pathogens undetectable by traditional methods. However, the efficacy of mNGS in the context of congenital heart disease infections remains uncertain. This study aimed to explore the diagnostic value of mNGS for respiratory virus infections post-CHS. Methods: We conducted a retrospective analysis of patients who developed respiratory tract infections post-CHS and were admitted to our cardiac center between July 2021 and December 2022. The patients were categorized into the following two groups based on the diagnostic method used: (I) the mNGS group (comprising 62 patients); and (II) the conventional microbiological test (CMT) group (comprising 70 patients). Bronchoalveolar lavage fluid (BALF) samples from these patients were tested to identify pathogens. Results: The mNGS group had significantly higher detection rates for both viral infections and mixed viral infections than the CMT group (56.45% vs. 17.14%, P<0.001, and 80.00% vs. 16.67%, P<0.001, respectively). In the mNGS group, 19.35% of the patients received antiviral therapy, and 61.29% received an anti-infective regimen adjustment. Conversely, in the CMT group, only 4.29% received antiviral therapy, and 28.57% received an anti-infective regimen adjustment. A higher percentage of patients showed improved respiratory symptoms in the mNGS group than the CMT group (74.19% vs. 44.29%, P=0.001). Additionally, the mNGS group had a shorter duration of mechanical ventilation and a reduced length of stay in the cardiac intensive care unit than the CMT group (P=0.012). Conclusions: Using mNGS for BALF enhances the detection of respiratory viral infections and coexisting viral infections post-CHS. This facilitates more precise treatment strategies and could potentially lead to improved patient outcomes.

7.
J Org Chem ; 89(7): 4840-4850, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38502550

RESUMO

Here, we report controlled and site-selective C-H alkenylation and dialkenylation of indolizines and pyrrolo[1,2-a]quinolines with ß-alkoxyvinyl trifluoromethylketones under simple and practical conditions. Moreover, this direct C-H alkenylation strategy can also be extended to imidazo[1,2-a]pyridines. Notably, without a transition metal and external oxidant, efficient dehydrogenative ß-alkenylation of tertiary amines with ß-alkoxyvinyl trifluoromethylketones is presented.

9.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473773

RESUMO

This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy.


Assuntos
Neoplasias Hepáticas , Nanopartículas , Humanos , Silício , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Galactosamina
10.
Pediatr Infect Dis J ; 43(4): 371-377, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306604

RESUMO

BACKGROUND: Neonates on extracorporeal membrane oxygenation (ECMO) are at high risk of infection. Rapid and accurate identification of pathogens is essential to improve the prognosis of children on ECMO. Metagenome next-generation sequencing (mNGS) has been used in recent years to detect pathogenic bacteria, but evidence for its use in neonates on ECMO is lacking. METHODS: This retrospective study was conducted using an electronic medical record system. We analyzed the results of mNGS and conventional microbiological tests (CMTs) in bronchoalveolar lavage fluid of neonates receiving ECMO support with pulmonary infections in our hospital from July 2021 to January 2023. RESULTS: We screened 18 ECMO-supported neonates with pneumonia for inclusion in the study. The median age of the included children was 2 (1-4) days, the median gestational age was 38.3 (33-40 +4 ) weeks, and the median weight was 3.3 (2.2-4.8) kg. The detection rate of mNGS was 77.8% (14/18), higher than the 44.4% (8/18) of CMT ( P = 0.04). A total of 20 pathogens were detected in mNGS, with the top 3 most common pathogens being Klebsiella pneumoniae , Acinetobacter baumannii and Escherichia coli . Mixed infections were found in 14 cases (77.8%), including 13 cases (72.2%) with mixed infections detected by mNGS and 7 cases (27.8%) with mixed infections detected by CMT. A total of 9 children underwent treatment changes based on mNGS results and all of them experienced relief of symptoms. CONCLUSION: Compared with CMT, mNGS can detect pathogens earlier and more sensitively, and may play an important role in ECMO-supported neonatal pneumonia pathogen detection and optimization of antibiotic therapy.


Assuntos
Coinfecção , Oxigenação por Membrana Extracorpórea , Pneumonia , Criança , Recém-Nascido , Humanos , Líquido da Lavagem Broncoalveolar , Metagenoma , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , Escherichia coli , Metagenômica , Sensibilidade e Especificidade
11.
Org Lett ; 26(6): 1255-1260, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38323865

RESUMO

The two novel cyclization modes of ß-CF3-1,3-enynes are presented herein for the divergent construction of F- and CF3-containing N-fused heterocycles. Fluorinated pyrazolo[1,5-a]pyridines were afforded from ß-CF3-1,3-enynes with N-aminopyridiniums ylides via detrifluoromethylative [2 + 3] cyclizations, followed by fluorine transfer from a CF3 unit. Whereas reaction with N-aminoisoquinoliniums ylides gave CF3-substituted pyrrolo[2,1-a]isoquinoline by unprecedented fragmentation [3 + 2]-cycloadditions. Additionally, gram-scale experiments and synthetic utility are demonstrated by further derivatization of fluorinated heterocycles.

12.
Sci Rep ; 14(1): 3655, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351050

RESUMO

This study aimed to investigate the association of lipid profile in early pregnancy and the risk of congenital heart disease (CHD) in offspring. This study was a prospective cohort design based on the Fujian Birth Cohort Study in China. We recruited pregnant women at ≤ 14 weeks of gestation between 2019 and 2022, and all participants in this study filled out the questionnaire about periconceptional exposure. Simultaneously, we collected participants' fasting blood samples to measure their lipid profile by automatic biochemical analyzer. The outcome was defined as offspring with CHD. A multivariable logistic regression model was used to calculate adjusted odds ratio (AOR) risk estimates, which indicate the associations between maternal lipid profiles and CHD in offspring. Restricted cubic splines were used to estimate their nonlinear relationship. A total of 21,425 pregnant women with an average gestational age of 11.3 (± 1.40) weeks were included in the analysis. The higher triglyceride (AOR 1.201, 95% CI [1.036, 1.394]), low-density lipoprotein (AOR 1.216, 95% CI [1.048, 1.410]), apolipoprotein B (Apo B) (AOR 2.107, 95% CI [1.179, 3.763]) levels were correlated with increased odds of CHD in offspring, while high-density lipoprotein (OR 0.672, 95% CI [0.490, 0.920]) related with decreased odds of CHD in offspring. The restricted cubic spline suggested a nonlinear relationship between total cholesterol (TC) levels and the risk of CHD in offspring (P = 0.0048), but no significant nonlinear relationships were found in other lipid profile. Apolipoprotein A was not related to the risk of CHD in offspring as either a continuous variable or a hierarchical variable. Elevated lipid profile in early pregnancy levels are associated with an increased risk of CHD in offspring. Additionally, there is a non-linear relationship between TC levels and the risk of CHD in offspring.


Assuntos
Cardiopatias Congênitas , Humanos , Feminino , Gravidez , Lactente , Estudos Prospectivos , Fatores de Risco , Estudos de Coortes , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/etiologia , Apolipoproteínas B
13.
J Cardiothorac Surg ; 19(1): 77, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336747

RESUMO

BACKGROUND: Complete atrioventricular septal defect is a complicated congenital heart malformations, and surgical correction is the best treatment, the severe tricuspid stenosis is a rare long-term complication after the surgery. CASE PRESENTATION: We report a case with the complication of severe tricuspid stenosis 7 years after the surgical correction of complete atrioventricular septal defect in a child. Then the patient underwent tricuspid mechanical valve replacement, Glenn, atrial septostomy, and circumconstriction of the right pulmonary artery. CONCLUSIONS: The patient recovered successfully with good short-term.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Defeitos dos Septos Cardíacos , Criança , Humanos , Constrição Patológica/complicações , Seguimentos , Defeitos dos Septos Cardíacos/cirurgia
14.
J Org Chem ; 89(5): 3590-3596, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364441

RESUMO

Under transition-metal-free conditions, trisulfide dioxides were used as disulfurating reagents to react with a wide range of amides, affording various substituted N-disulfanyl amides in good yields. Furthermore, the gram-scale experiment has confirmed the practicability of this approach.

15.
J Insect Physiol ; 153: 104619, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301801

RESUMO

Extreme temperatures threaten species under climate change and can limit range expansions. Many species cope with changing environments through plastic changes. This study tested phenotypic changes in heat and cold tolerance under hardening and acclimation in the melon thrips, Thrips palmi Karny (Thysanoptera: Thripidae), an agricultural pest of many vegetables. We first measured the critical thermal maximum (CTmax) of the species by the knockdown time under static temperatures and found support for an injury accumulation model of heat stress. The inferred knockdown time at 39 °C was 82.22 min. Rapid heat hardening for 1 h at 35 °C slightly increased CTmax by 1.04 min but decreased it following exposure to 31 °C by 3.46 min and 39 °C by 6.78 min. Heat acclimation for 2 and 4 days significantly increased CTmax at 35 °C by 1.83, and 6.83 min, respectively. Rapid cold hardening at 0 °C and 4 °C for 2 h, and cold acclimation at 10 °C for 3 days also significantly increased cold tolerance by 6.09, 5.82, and 2.00 min, respectively, while cold hardening at 8 °C for 2 h and acclimation at 4 °C and 10 °C for 5 days did not change cold stress tolerance. Mortality at 4 °C for 3 and 5 days reached 24.07 % and 43.22 % respectively. Our study showed plasticity for heat and cold stress tolerance in T. palmi, but the thermal and temporal space for heat stress induction is narrower than for cold stress induction.


Assuntos
Termotolerância , Tisanópteros , Animais , Temperatura Baixa , Aclimatação , Temperatura
16.
Biomed Environ Sci ; 37(1): 54-70, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38326721

RESUMO

Objective: The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction. Methods: Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting. Results: They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1ß, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group. Conclusion: Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.


Assuntos
Lipopolissacarídeos , Quercetina , Embrião de Galinha , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Lipopolissacarídeos/toxicidade , Metaloproteinase 9 da Matriz , Caspase 3 , Metaloproteinase 3 da Matriz , Receptor 4 Toll-Like , Claudina-1 , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Apoptose , RNA Mensageiro , Autofagia , NF-kappa B
17.
Acta Pharm Sin B ; 14(2): 468-491, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322325

RESUMO

G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.

18.
Curr Res Food Sci ; 8: 100699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420347

RESUMO

Alcohol liver disease (ALD) is a liver disease caused by long-term heavy drinking. Glucosamine (GLC) is an amino monosaccharide that plays a very important role in the synthesis of human and animal cartilage. GLC is commonly used in the treatment of mild to moderate osteoarthritis and has good anti-inflammatory and antioxidant properties. In this study, alcoholic injury models were constructed in mice and human normal hepatocyte L02 cells to explore the protective effect and mechanism of GLC on ALD. Mice were given GLC by gavage for 30 days. Liver injury models of both mice and L02 cells were produced by ethanol. Detecting the levels of liver injury biomarkers, lipid metabolism, oxidative stress biomarkers, and inflammatory factors through different reagent kits. Exploring oxidative and inflammatory pathways in mouse liver tissue through Western blot and RT-PCR. The results showed that GLC can significantly inhibit the abnormal increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), and can significantly improve the level of high-density lipoprotein cholesterol (HDL-C). In addition, GLC intervention significantly improved alcohol induced hepatic oxidative stress by reducing the levels of malondialdehyde (MDA) and, increasing the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the liver. Further mechanisms suggest that GLC can inhibit the expression of ethanol metabolism enzyme cytochrome P4502E1 (CYP2E1), activate the antioxidant pathway Keap1/Nrf2/HO-1, down-regulate the phosphorylation of MAPK and NF-κB signaling pathways, and thus reduce the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Therefore, GLC may be a significant candidate functional food for attenuating alcohol induced acute liver injury.

19.
Rheumatology (Oxford) ; 63(1): 251-258, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37184873

RESUMO

OBJECTIVES: Galectin-9, as immune checkpoint protein, plays a role in regulating autoimmunity and tumour immunity. Therefore, we explored the pathophysiological link between galectin-9 and malignancy in cancer-related DM (CRDM). METHODS: Serum galectin-9 were quantified via enzyme-linked immunosorbent assay, and its association with serological indices was evaluated using Spearman analysis. Receiver operating characteristic (ROC) analysis was utilized to determine the cut-off value of galectin-9. RESULTS: Serum levels of galectin-9 were significantly higher in DM patients [23.38 (13.85-32.57) ng/ml] than those in healthy controls (HCs) [6.81 (5.42-7.89) ng/ml, P < 0.0001], and were positively correlated with the cutaneous dermatomyositis disease area severity index activity (CDASI-A) scores (rs=0.3065, P = 0.0172). DM patients with new-onset and untreated cancer (new-CRDM) [31.58 (23.85-38.84) ng/ml] had higher levels of galectin-9 than those with stable and treated cancer (stable-CRDM) [17.49 (10.23-27.91) ng/ml, P = 0.0288], non-cancer-related DM (non-CRDM) [21.05 (11.97-28.02) ng/ml, P = 0.0258], and tumour patients without DM [7.46 (4.90-8.51) ng/ml, P < 0.0001]. Serum galectin-9 levels significantly decreased [27.79 (17.04-41.43) ng/ml vs 13.88 (5.15-20.37) ng/ml, P = 0.002] after anti-cancer treatment in CRDM patients. The combination of serum galectin-9 and anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibody (AUC = 0.889, 95% CI 0.803-0.977) showed the highest predictive value for the presence of cancer in DM. CONCLUSION: Increased galectin-9 levels were related to tumor progression in CRDM, and galectin-9 was downregulated upon cancer treatment. Monitoring serum galectin-9 levels and anti-TIF1-γ antibodies might be an attractive strategy to achieve tumour diagnosis and predict CRDM outcome.


Assuntos
Dermatomiosite , Neoplasias , Humanos , Dermatomiosite/complicações , Neoplasias/complicações , Galectinas , Anticorpos , Biomarcadores , Autoanticorpos
20.
Ann Thorac Cardiovasc Surg ; 30(1)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-37394498

RESUMO

PURPOSE: To investigate the effect of optimizing regional cerebral oxygen saturation (rScO2) on the incidence of postoperative delirium and surgical outcome in infants with congenital heart disease. METHODS: Sixty-one infants experienced desaturation in rScO2 of 10% from baseline for more than 30 seconds during surgery between January 2020 and January 2022. Among them, 32 cases (Group A) received the corresponding treatment in the process of desaturation and 29 cases (Group B) were observed without receiving any treatment. General information, cerebral oxygen saturation, the incidence of postoperative delirium, and other relevant clinical data were collected. RESULTS: The duration and severity of intraoperative rScO2 desaturation in Group A were significantly lower than those in Group B. The incidence of postoperative delirium in Group A was significantly lower than that in Group B. There was no significant difference in the positive screening score for delirium between the two groups. Binary logistic regression analysis showed that the aortic cross-clamp time, mechanical ventilation duration, and severity of intraoperative rScO2 desaturation were significantly correlated with the occurrence of postoperative delirium. CONCLUSION: Aggressive rScO2 desaturation treatment is associated with a lower incidence of postoperative delirium and improved surgical outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Delírio do Despertar , Lactente , Humanos , Estudos Retrospectivos , Incidência , Saturação de Oxigênio , Oxigênio , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Cardíacos/efeitos adversos
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