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1.
Cell ; 187(9): 2129-2142.e17, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670071

RESUMO

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.


Assuntos
Prosencéfalo , Animais , Prosencéfalo/metabolismo , Prosencéfalo/embriologia , Camundongos , Ratos , Blastocisto/metabolismo , Feminino , Sistemas CRISPR-Cas/genética , Transcriptoma , Organogênese , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Masculino , Camundongos Endogâmicos C57BL
2.
PLoS Pathog ; 20(4): e1012075, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568937

RESUMO

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.


Assuntos
COVID-19 , Infecção Hospitalar , Microbiota , Humanos , SARS-CoV-2/genética , Bactérias , Microbiota/genética
3.
Chem Soc Rev ; 53(16): 8379-8423, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39007174

RESUMO

Nitrous oxide (N2O) decomposition is increasingly acknowledged as a viable strategy for mitigating greenhouse gas emissions and addressing ozone depletion, aligning significantly with the UN's sustainable development goals (SDGs) and carbon neutrality objectives. To enhance efficiency in treatment and explore potential valorization, recent developments have introduced novel N2O reduction catalysts and pathways. Despite these advancements, a comprehensive and comparative review is absent. In this review, we undertake a thorough evaluation of N2O treatment technologies from a holistic perspective. First, we summarize and update the recent progress in thermal decomposition, direct catalytic decomposition (deN2O), and selective catalytic reduction of N2O. The scope extends to the catalytic activity of emerging catalysts, including nanostructured materials and single-atom catalysts. Furthermore, we present a detailed account of the mechanisms and applications of room-temperature techniques characterized by low energy consumption and sustainable merits, including photocatalytic and electrocatalytic N2O reduction. This article also underscores the extensive and effective utilization of N2O resources in chemical synthesis scenarios, providing potential avenues for future resource reuse. This review provides an accessible theoretical foundation and a panoramic vision for practical N2O emission controls.

4.
J Transl Med ; 22(1): 746, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113144

RESUMO

Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.


Assuntos
Ácidos e Sais Biliares , Fezes , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Ácidos e Sais Biliares/metabolismo , Humanos , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/microbiologia , Microbioma Gastrointestinal/imunologia , Feminino , Masculino , Fezes/microbiologia , Pessoa de Meia-Idade , Doença Aguda , Adulto , Retroalimentação Fisiológica , Imunidade , Metabolômica , Transplante de Células-Tronco Hematopoéticas , Multiômica
5.
Cytokine ; 184: 156758, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39299100

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive. METHODS: Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion. RESULTS: Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells. CONCLUSIONS: Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.

6.
Liver Int ; 44(10): 2564-2571, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38963300

RESUMO

BACKGROUND AND AIMS: Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ-poisoned patients. METHODS: We conducted a retrospective cohort study of PQ-poisoned patients from the past 10 years (2011-2020) from a large tertiary academic medical centre in China. PQ-poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. RESULTS: A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p < .001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. CONCLUSIONS: The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Paraquat , Humanos , Paraquat/intoxicação , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Herbicidas/intoxicação , Fatores de Risco , Pontuação de Propensão , Testes de Função Hepática
7.
BMC Infect Dis ; 24(1): 426, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649799

RESUMO

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.


Assuntos
Infecções Respiratórias , Humanos , China/epidemiologia , Estudos Retrospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Doença Aguda , Lactente , Idoso de 80 Anos ou mais , Vírus/isolamento & purificação , Vírus/classificação , Vírus/genética , Hospitalização/estatística & dados numéricos
8.
Am J Emerg Med ; 84: 149-157, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127020

RESUMO

AIM: The aim of this study was to summarize the existing evidence about the effectiveness of double defibrillation (DD) in comparison to standard defibrillation for patients with refractory ventricular fibrillation (RVF). DD encompasses double "sequential" external defibrillation (DSeq-D) and double "simultaneous" defibrillation (DSim-D), with the study also shedding light on the respective effects of DSeq-D and DSim-D. METHODS: Investigators systematically searched PubMed, EMBASE and Cochrane Central databases for randomized controlled trials (RCTs) and cohort studies from their inception until June 06, 2024. The rate of survival to hospital discharge was the primary outcome, while the incidence of return of spontaneous circulation (ROSC), termination of ventricular fibrillation (VF), survival to hospital admission and good neurologic outcome were secondary outcomes. Relative ratios (RR) and 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity was assessed using I square value. RESULTS: A total of 6 trials, comprising 1360 patients, were included. One was an RCT, and five were observational cohort studies. The RCT showed that, compared to standard defibrillation, DSeq-D was associated with higher incidences of survival to hospital discharge, termination of VF, ROSC and good neurologic outcome. However, the pooled results of cohort studies found no benefit of DD over standard defibrillation in survival to hospital discharge (RR, 0.91; 95% CI, 0.46-1.78), nor in secondary outcomes. Furthermore, subgroup analysis suggested DSim-D was linked with lower ROSC rate compared to standard defibrillation (RR, 0.65; 95% CI, 0.49-0.86), while there was no significance between DSeq-D and standard defibrillation (RR, 1.00; 95% CI, 0.70-1.42). CONCLUSIONS: The benefit of DSeq-D in survival to hospital discharge for RVF patients was found in the RCT, but not in cohort studies. Additionally, DSim-D should be applied with greater caution for RVF patients. Further validation is needed through larger-scale and higher-quality trials. TRIAL REGISTRY: INPLASY; Registration number: INPLASY202340015; URL: https://inplasy.com/.


Assuntos
Cardioversão Elétrica , Fibrilação Ventricular , Humanos , Cardioversão Elétrica/métodos , Cardioversão Elétrica/estatística & dados numéricos , Fibrilação Ventricular/complicações , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/terapia
9.
J Dairy Sci ; 107(10): 7533-7548, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38851568

RESUMO

This article summarizes the applications of biosensors and biomimetic sensors in the detection of residues in dairy products. Biosensors use biological molecules, such as enzymes or antibodies, to detect residual substances in dairy products, demonstrating high specificity and sensitivity. Biomimetic sensors, inspired by biosensors, use synthetic materials to mimic biological sensing mechanisms, enhancing stability and reproducibility. Both sensor types have achieved notable success in detecting pesticide residues, veterinary drugs, bacteria, and other contaminants in dairy products. The applications of biological and biomimetic sensors not only improve the efficiency of residue detection in dairy products but also have the potential to reduce the time and cost of traditional methods. Their specificity and high sensitivity make them powerful tools in the dairy industry, thus contributing to ensuring the quality and safety of dairy products and meeting the growing consumer demands for health and food safety.


Assuntos
Técnicas Biossensoriais , Laticínios , Técnicas Biossensoriais/instrumentação , Laticínios/análise , Animais , Biomimética , Contaminação de Alimentos/análise
10.
J Dairy Sci ; 107(7): 4370-4380, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38246548

RESUMO

Adequate energy supply is a crucial factor for maintaining the production performance in cows during the early lactation period. Adding fatty acids (FA) to diets can improve energy supply, and the effect could be related to the chain length and degree of saturation of those FA. This study was conducted to evaluate the effect of different ratios of palmitic acid (C16:0) to oleic acid (cis-9 C18:1) on the production performance, nutrient digestibility, blood metabolites, and milk FA profile in early lactation dairy cows. Seventy-two multiparous Holstein cows (63.5 ± 2.61 days in milk) blocked by parity (2.39 ± 0.20), body weight (668.3 ± 20.1 kg), body condition score (3.29 ± 0.06), and milk yield (47.9 ± 1.63 kg) were used in a completely randomized design. Cows were divided into 3 groups with 24 cows in each group. Cows in the 3 treatment groups were provided iso-energy and iso-nitrogen diets, but the C16:0 to cis-9 C18:1 ratios were different: (1) 90.9% C16:0 + 9.1% cis-9 C18:1 (90.9:9.1); (2) 79.5% C16:0 + 20.5% cis-9 C18:1 (79.5:20.5); and (3) 72.7% C16:0 + 27.3% cis-9 C18:1 (72.7:27.3). Fatty acids were added at 1.3% on a dry matter basis. Although the dry matter intake fat-corrected milk yield and energy-corrected milk yield were not affected, the milk yield, milk protein yield, and feed efficiency increased linearly with increasing cis-9 C18:1 ratio. The milk protein percentage and milk fat yield did not differ among treatments, whereas the milk fat percentage tended to decrease linearly with the increasing cis-9 C18:1 ratio. The lactose yield increased linearly and lactose percentage tended to increase linearly with increasing cis-9 C18:1 ratio, but the percentage of milk total solids and somatic cell count decreased linearly. Although body condition scores were not affected by treatments, body weight loss decreased linearly with increasing cis-9 C18:1 ratio. The effect of treatment on nutrient digestibility was limited, except for a linear increase in ether extract and neutral detergent fiber digestibility with increasing cis-9 C18:1 ratio. There was a linear increase in the concentration of plasma glucose, but the triglyceride and nonesterified FA concentrations decreased linearly with increasing cis-9 C18:1 ratio. As the cis-9 C18:1 ratio increased, the concentration of de novo FA decreased quadratically, but the mixed and preformed fatty acids increased linearly. In conclusion, increasing cis-9 C18:1 ratio could increase production performance and decrease body weight loss by increasing nutrient digestibility, and the ratio that had the most powerful beneficial effect on early lactation cows was 72.7:27.3 (C16:0 to cis-9 C18:1).


Assuntos
Ração Animal , Dieta , Ácidos Graxos , Lactação , Leite , Ácido Oleico , Ácido Palmítico , Animais , Bovinos , Feminino , Lactação/efeitos dos fármacos , Leite/química , Leite/metabolismo , Dieta/veterinária , Ácido Oleico/farmacologia , Ácidos Graxos/análise , Nutrientes/metabolismo , Digestão/efeitos dos fármacos
11.
Opt Express ; 31(6): 9961-9972, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157559

RESUMO

We investigate the propagation dynamics of the soliton-sinc, a kind of novel hybrid pulse, in the presence of higher-order effects with emphasis on the third-order dispersion (TOD) and Raman effects. At variance with the fundamental sech soliton, the traits of the band-limited soliton-sinc pulse can effectively manipulate the radiation process of dispersive waves (DWs) induced by the TOD. The energy enhancement and the radiated frequency tunability strongly depend on the band-limited parameter. A modified phase-matching condition is proposed for predicting the resonant frequency of the DWs emitted by soliton-sinc pulses, which is verified by the numerically calculated results. In addition, Raman-induced frequency shift (RIFS) of the soliton sinc pulse increases exponentially with a decrease of the band-limited parameter. Finally, we further discuss the simultaneous contribution of the Raman and TOD effects to the generation of the DWs emitted from the soliton-sinc pulses. The Raman effect can then either reduce or amplify the radiated DWs depending on the sign of the TOD. These results show that soliton-sinc optical pulses should be relevant for practical applications such as broadband supercontinuum spectra generation as well as nonlinear frequency conversion.

12.
Opt Lett ; 48(24): 6529-6532, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099791

RESUMO

We investigate the dispersive waves (DWs) emitted from shaped pulses with spectral Heaviside step phases (HSPs). The spectrally HSP-modulated pulse exhibits a unique double-peak structure, where the intensity and separation of the twin peaks are determined by the modulation depth and frequency detuning. By tailoring the parameters of the HSP suitably, we can control the DW emission with regard to resonant frequency and conversion efficiency. As the intensity ratio or relative separation of neighboring peaks is elaborately chosen, the DW emission can be effectively boosted, or a solitonic cage can be constructed for realizing temporal reflections and refractions associated with spectral broadening and multi-peak spectra of the output DWs. These findings offer a straightforward and efficient approach for controlling the DW emission, which is highly relevant to the advancement of supercontinuum generation and wavelength conversion technology.

13.
Phytother Res ; 37(6): 2405-2418, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36752274

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease around the world, imposing severe threats on human health. Unfortunately, no clinically approved drugs are available for use as yet. Baicalin (BA) is reported to have hepatoprotective effects, and it is not clear whether BA can treat NAFLD and how. Here, a high-fat diet (HFD)-induced NAFLD mouse model was established to explore the protective roles and mechanisms of BA against HFD-induced NAFLD. Physiochemical results showed that BA exhibited significantly protective effects against HFD-induced NAFLD in mice. Liver transcriptomic analysis revealed that BA attenuated HFD-induced NAFLD via activating AMPK pathway, which was confirmed by the AMPK inhibitor Compound C. Additionally, the expression changes of AMPK downstream genes demonstrated that BA exerted ameliorative effects against NAFLD through AMPK-mediated inhibition of SREBP1 and NF-κB pathways, and activation of Nrf2 pathway. Taken together, our study reveals the protective roles of BA against HFD-caused NAFLD through AMPK-mediated modulation of SREBP1/Nrf2/NF-κB pathways, suggesting that BA has potential drug development implications. Most importantly, our study creates a paradigm through the combination of molecular biology and bioinformatics for further studies of action mechanisms of biomolecules combating diseases.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais
14.
Pestic Biochem Physiol ; 197: 105647, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38072522

RESUMO

Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial-mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-ß1/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-ß1/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.


Assuntos
Paraquat , Fibrose Pulmonar , Humanos , Camundongos , Animais , Paraquat/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/uso terapêutico , 2-Metoxiestradiol/farmacologia , 2-Metoxiestradiol/uso terapêutico , Camundongos Endogâmicos C57BL , Transdução de Sinais
15.
Molecules ; 28(10)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37241934

RESUMO

Neonicotinoids (NEOs) have become the most widely used insecticides in the world since the mid-1990s. According to Chinese dietary habits, rice and water are usually heated before being consumed, but the information about the alteration through the heat treatment process is very limited. In this study, NEOs in rice samples were extracted by acetonitrile (ACN) and in tap water, samples were extracted through an HLB cartridge, then, a high-performance liquid chromatography system and a triple quadrupole mass spectrometry (HPLC-MS/MS) were applied for target chemical analysis. The parents of NEOs (p-NEOs) accounted for >99% of the total NEOs mass (∑NEOs) in both uncooked (median: 66.8 ng/g) and cooked (median: 41.4 ng/g) rice samples from Guangdong Province, China, while the metabolites of NEOs (m-NEOs) involved in this study accounted for less than 1%. We aimed to reveal the concentration changes of NEOs through heat treatment process, thus, several groups of rice and water samples from Guangdong were cooked and boiled, respectively. Significant (p < 0.05) reductions in acetamiprid, imidacloprid (IMI), thiacloprid, and thiamethoxam (THM) have been observed after the heat treatment of the rice samples. In water samples, the concentrations of THM and dinotefuran decreased significantly (p < 0.05) after the heat treatment. These results indicate the degradation of p-NEOs and m-NEOs during the heat treatment process. However, the concentrations of IMI increased significantly in tap water samples (p < 0.05) after heat treatment process, which might be caused by the potential IMI precursors in those industrial pesticide products. The concentrations of NEOs in rice and water can be shifted by the heat treatment process, so this process should be considered in relevant human exposure studies.


Assuntos
Água Potável , Inseticidas , Oryza , Humanos , Água Potável/análise , Espectrometria de Massas em Tandem/métodos , Temperatura Alta , Cromatografia Gasosa-Espectrometria de Massas , Neonicotinoides/análise , Inseticidas/análise , Tiametoxam/análise , Nitrocompostos/análise , China
17.
Physiol Mol Biol Plants ; 29(4): 543-557, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37187770

RESUMO

Soil salinization has become one of the major abiotic stresses influencing food security and maintenance of sustainable eco-environment. Highly salt-tolerant germplasm in mulberry, an important perennial woody plant, could restore the ecology and increase the agricultural income. Studies on the salt tolerance of mulberry are limited. Therefore, the aim of this study was to estimate the genetic variation and develop a reliable and effective evaluation of salt tolerance in 14 F1 mulberry hybrids that were directionally constructed using nine genotypes, including two females and seven males. A salt stress test was performed using 0.3%, 0.6%, and 0.9% (w/v) NaCl to investigate four morphological indexes of the growth rate: the shoot height (SHR), leaf number (LNR), leaf area (LAR), and the total weight of the whole plant after defoliation (BI) in the seedlings of the 14 combinations. The most suitable concentration for evaluating salt tolerance was identified as 0.9% NaCl based on the changes in the salt tolerance coefficient (STC). Comprehensive evaluation (D) values were obtained using principal components and membership functions based on four morphological indexes and their STCs, grouped into three principal component indexes cumulatively contributing to approximately 88.90% of the total variance. Two highly salt-tolerant, three moderately salt-tolerant, five salt-sensitive, and four highly salt-sensitive genotypes were screened. Anshen × Xinghainei and Anshen × Xinghaiwai had the highest D values. The analyses of combining ability further showed that the variances for LNR, LAR, and BI were elevated significantly with the increasing NaCl concentrations. Anshen × Xinghainei from two superior parents (female: Anshen, male: Xinghainei) with relatively higher general combing abilities for SHR, LAR, and BI was the best hybrid combination under high salinity stress, and presented the best specific combining ability for BI. Of all the traits tested, LAR and BI were greatly affected by additive effects and might be the two most reliable indexes. These traits show higher correlation with the salt tolerance of mulberry germplasm at the seedling stage. These results may enrich the mulberry resources by breeding and screening for elite germplasms with high salt tolerance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01304-w.

18.
Ann Vasc Surg ; 79: 290-297, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34648852

RESUMO

BACKGROUND: We aimed to investigate the formation and self-healing process of rabbit abdominal aortic aneurysm (AAA) by focus on the degeneration and regeneration of smooth muscle cells (SMCs) in elastase-induced AAA model and enlarging AAA model in rabbits. METHODS: Sixty rabbits were equally divided into 2 aneurysm groups (Group A and Group B). Rabbits received a 10-min incubation of elastase in Group A (10 units/µL) and Group B (1 unit/µL). Rabbits underwent aortic stenosis above the incubated segment in Group B. Aortic diameter was measured and rabbits were sacrificed for histopathological and immunohistochemical studies. RESULTS: The incubated aorta dilated immediately and ran up to maxima by day 21 in Group A. All aneurysms formed by day 21 and enlarged progressively in Group B. SMCs content, elastin content and intima-media thickness decreased significantly by day 0 in Group A. SMCs and elastic fibers were destroyed gradually in Group B, however, SMCs content was significantly lower than Group A by day 70. Intimal thickness increased significantly by day 70 in the Aneurysm groups. MMP2 maintained moderate expression in Group A, which decreased significantly by day 3 in Group B. MMP9 and RAM11 expressions were higher by day 1, but decreased significantly by day 3 in Group B. CONCLUSIONS: Irreversible degeneration of SMCs is critical to a rapid formation of elastase-induced rabbit AAA model, and SMCs excessive regeneration accounts for the selfhealing process. SMCs degradation and regeneration remain relatively stable in an enlarging AAA model. SMCs should be the key target for studying the mechanism of AAA and intervention therapy.


Assuntos
Aneurisma da Aorta Abdominal/patologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Regeneração , Remodelação Vascular , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Abdominal/fisiopatologia , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/fisiopatologia , Dilatação Patológica , Modelos Animais de Doenças , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Elastina/metabolismo , Ligadura , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Elastase Pancreática , Coelhos , Fatores de Tempo
19.
J Dairy Sci ; 105(4): 3019-3031, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35086700

RESUMO

As a food adapted to all kinds of people, milk has a high nutritional value. Because milk is a complex biological matrix, detecting illegal compounds is often difficult. As a common pesticide, organophosphorus (OP) residues caused by nonstandard use may be ignored, which is a threat to milk quality. In this study, using coumaphos as template molecule, the synthesized molecularly imprinted polymer (MIP) can specifically recognize 7 kinds of OP. Then, the MIP was used as an identification element to prepare a chemiluminescence sensor on a 96-well microplate for the determination of OP residues in milk samples. Due to the 4-(imidazol-1-yl)phenol-enhanced luminol-H2O2 system, the sensitivity of the system is very high; the detection limits of 7 OP including coumaphos, fenthion, chlorpyrifos, parathion, diazinon, fenchlorphos, and fenitrothion were 1 to 3 pg/mL, and the half maximal inhibitory concentrations were 1 to 20 ng/mL. The intraday recoveries of 7 OP were in the range of 86.1 to 86.5%, and the interday recoveries were in the range of 83.6 to 94.2%. Furthermore, the sensor can be reused up to 5 times. Therefore, the MIP-based chemiluminescence sensor can be used as a routine tool to detect OP residues in milk samples.


Assuntos
Impressão Molecular , Animais , Humanos , Peróxido de Hidrogênio/química , Luminescência , Leite , Impressão Molecular/veterinária , Polímeros Molecularmente Impressos , Polímeros/química
20.
Immunopharmacol Immunotoxicol ; 44(3): 306-315, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35238277

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is a life-threatening disorder associated with multisystem organ failure. This study aimed to investigate the function of high mobility group box 1 (HMGB1) in SAP-induced myocardial injury. METHODS: A rat model with SAP was induced. The pathological changes in rat pancreatic and cardiac tissues were examined by HE staining. Cardiomyocyte apoptosis in rat cardiac tissues, and the serum levels of myocardial injury markers and pro-inflammatory cytokines were examined. Rat primary cardiomyocytes were treated with H2O2 for in vitro experiments. The regulatory molecules of HMGB1 were predicted by bioinformatics analysis. Altered expression of HMGB1, microRNA (miR)-340-5p and CCCTC-binding factor (CTCF) was introduced in rats or cells to investigate their roles in myocardial injury. RESULTS: CTCF and HMGB1 were highly expressed but miR-340-5p was poorly expressed in cardiac tissues of rats with SAP. HMGB1 silencing reduced toll-like receptor 4 (TLR4) expression to promote proliferation and reduce apoptosis of H2O2-treated cardiomyocytes. miR-340-5p targeted HMGB1 mRNA, while CTCF suppressed miR-340-5p transcription. CTCF upregulation or miR-340-5p downregulation blocked the effects of HMGB1 silencing on cardiomyocytes. In vivo, CTCF silencing alleviated injury in rat pancreatic and cardiac tissues and reduced the expression of creatine kinase-MB (CK-MB), lactic dehydrogenase, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) in rat serum. But further overexpression of HMGB1 or inhibition of miR-340-5p aggravated the symptoms in rats. CONCLUSION: This study demonstrated that CTCF reduces transcription of miR-340-5p to promote HMGB1 expression, which activates TLR4 expression and promotes myocardial injury in rats with SAP.


Assuntos
Proteína HMGB1 , MicroRNAs , Pancreatite , Animais , Ratos , Doença Aguda , Apoptose/genética , Fator de Ligação a CCCTC/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Peróxido de Hidrogênio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/genética , Pancreatite/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
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