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1.
Virulence ; 15(1): 2397492, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39239724

RESUMO

Coronavirus nonstructural protein 2 (Nsp2) is regarded as a virulence determinant and plays a critical role in virus replication, and innate immunity. Screening and identifying host cell proteins that interact with viral proteins is an effective way to reveal the functions of viral proteins. In this study, the host proteins that interacted with transmissible gastroenteritis virus (TGEV) Nsp2 were identified using immunoprecipitation combined with LC-MS/MS. 77 host cell proteins were identified as putative Nsp2 interaction host cell proteins and a protein-protein interaction (PPI) was constructed. The identified proteins were found to be associated with various subcellular locations and functional categories through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. It is hypothesized that the host cell proteins interacting with TGEV Nsp2 are mainly involved in the formation of the cytoplasmic translation initiation complex, mRNA binding, ribosomes, and proteasomes. Among these, the ATP5B, a core subunit of the mitochondrial ATP synthase was further studied. The Coimmunoprecipitation (Co-IP) and indirect immunofluorescence (IFA) results confirmed that TGEV Nsp2 interacted with ATP5B. Furthermore, the downregulation of ATP5B expression was found to promote TGEV replication, suggesting that ATP5B might function as a negative regulator of TGEV replication. Collectively, our results offer additional insights into the functions of Nsp2 and provide a novel antiviral target against TGEV.


Assuntos
ATPases Mitocondriais Próton-Translocadoras , Vírus da Gastroenterite Transmissível , Proteínas não Estruturais Virais , Replicação Viral , Vírus da Gastroenterite Transmissível/genética , Animais , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Suínos , ATPases Mitocondriais Próton-Translocadoras/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Humanos , Interações Hospedeiro-Patógeno , Gastroenterite Suína Transmissível/virologia , Gastroenterite Suína Transmissível/genética , Linhagem Celular , Imunoprecipitação , Espectrometria de Massas em Tandem
2.
Arch Sex Behav ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327375

RESUMO

Mental health disparities in transgender and gender diverse (TGD) populations call for more research examining gender minority stressors (GMS) as antecedents to their psychological distress, especially for the long-underrepresented groups living in conservative societies towards gender minorities. Furthermore, some questions remain underexamined, including the relative, independent influences of various GMS on TGD people's mental well-being (i.e., uniqueness of each stressor); how these stressors would configurate with each other in distinctive patterns to characterize subgroups of TGD people (i.e., beyond-average heterogeneity); and how these stressors would constitute a psychological network and vary in their centrality in that network (i.e., holistic complexity). To narrow such gaps, we examined the links between GMS and TGD people's psychological distress, using survey data collected in 2023 from 410 Chinese TGD people (Meanage = 22.33 years, SD = 4.27; 306 transgender, 70 non-binary/gender-queer/gender-fluid, 26 agender/gender-neutral, 3 intersex, and 5 others). We approached such links from three perspectives. First, variable-centered analyses indicated that while different GMS were considered simultaneously, internalized transphobia, preoccupation with gender dysphoria, and gender-related victimization were uniquely associated with psychological distress. Second, person-centered analyses yielded a 3-profile solution. Psychological distress varied systematically across profiles. Last, network analyses revealed a 3-cluster structure: Distal, Proximal Internal, and TGD-Specific Stressors. Preoccupation with gender dysphoria was the most central node. These findings contribute to a more nuanced understanding of the implications of GMS for TGD people's mental well-being. GMS related to internal struggles with gender identity might be among the central intervention targets to prevent/reduce TGD people's psychological distress.

3.
J Clin Pharmacol ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141421

RESUMO

This parallel-group, open-label Phase I study evaluated the effect of mild to moderate hepatic impairment on pharmacokinetics (PK), pharmacodynamics (PD), and safety of a single oral dose of SHR4640. Participants with mild or moderate hepatic impairment were enrolled, with each cohort consisting of eight individuals, alongside eight well-matched controls with normal hepatic function. The participants were administered 10 mg SHR4640, and blood samples were collected for PK evaluation over 72 h. Additionally, serum uric acid (sUA) levels were measured to assess PD changes. Safety was evaluated through adverse events, laboratory tests, vital signs, and electrocardiograms. The Cmax of SHR4640 decreased by 15.0% in the mild hepatic impairment group (geometric least squares means of the ratios [GMR] = 0.850, 90% CI: 0.701-1.03) and by 17.5% in the moderate hepatic impairment group (GMR = 0.825, 90% CI: 0.681-1.00). These reductions were not statistically significant compared to the normal hepatic function group. AUC0-t and AUC0-inf were similar across all groups, indicating that overall exposure to the drug was not clinical significantly affected by hepatic impairment. Apparent clearance and volume of distribution of SHR4640 showed no association with the severity of hepatic impairment as measured by the Child-Pugh score. There were no significant differences in the changes in sUA levels from baseline across different levels of hepatic function. SHR4640 is well tolerated in participants with mild or moderate hepatic impairment. Mild and moderate hepatic impairment did not have a clinically relevant impact on PK, PD, and safety of SHR4640. SHR4640 can be used in patients with mild to moderate hepatic impairment without the need for dose adjustment.

4.
Int J Eat Disord ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177303

RESUMO

OBJECTIVE: Weight bias internalization (WBI) is a robust, positive correlate of negative health outcomes; however, this evidence base primarily reflects cisgender individuals from Western cultural contexts. Gender-diverse individuals from non-Western cultural contexts (e.g., China) are at potentially high risk for WBI. Yet, no research has examined WBI and associated negative health consequences in this historically underrepresented population. METHOD: A cross-sectional, online survey sampled Chinese gender-diverse individuals (N = 410, Mage = 22.33 years). Variables were self-reported, including demographics, WBI, body shame, body dissatisfaction, disordered eating, physical and mental health status, and gender minority stress (e.g., internalized cisgenderism). Analyses included correlations and multiple hierarchical regressions. RESULTS: Pearson bivariate correlations demonstrated associations between higher WBI and more eating and body image disturbances and poor physical and mental health. After adjusting for age, BMI, gender identity, and gender minority stress, higher WBI was uniquely and positively associated with higher body shame, higher body dissatisfaction, higher disordered eating, and poor physical and mental health. Notably, WBI accounted for more unique variance in eating and body image disturbances (13%-25% explained by WBI) than physical and mental health (1%-4% explained by WBI). DISCUSSION: While replication with longitudinal and experimental designs is needed to speak to the temporal dynamics and causality, our findings identify WBI as a unique, meaningful correlate of eating and body image disturbances in Chinese gender-diverse adults.

5.
Bioresour Technol ; 406: 131074, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971393

RESUMO

The development of biodegradable antimicrobial bioplastics for food packaging holds great promise for solving the pollution and safety problems caused by petrochemical plastics and spoiled food. Herein, a natural active-bioplastic synthesized from citrus peel biomass is presented for perishable fruit preservation. These plastics are characterized by the nanoscale entanglement and recombinant hydrogen bonding between the endogenous pectin, polyphenols and cellulose micro/nanofibrils. They have attractive flexibility, tensile strength, gas barrier properties and antimicrobial activities, and can effectively extend the shelf life of perishable fruits such as banana and mango when used as food packaging. Cytotoxicity, degradability tests and life-cycle assessment show that these plastics had excellent nontoxicity and can be safely degraded or easily recycled. This work demonstrates a sustainable strategy for converting peel waste into eco-friendly bioplastics, providing a unique and novel insight into radically reducing the pollution and life-health threats posed by petrochemical plastics and spoiled food.


Assuntos
Anti-Infecciosos , Frutas , Frutas/química , Anti-Infecciosos/farmacologia , Plásticos Biodegradáveis/farmacologia , Plásticos Biodegradáveis/química , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Citrus/química , Reciclagem , Plásticos/química , Plásticos/farmacologia , Resistência à Tração , Polifenóis/farmacologia , Polifenóis/química , Biodegradação Ambiental
6.
Front Nutr ; 11: 1366525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953045

RESUMO

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019. Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software. Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030. Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38936599

RESUMO

OBJECTIVE: Left ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from recurrent left ventricular outflow tract obstruction (LVOTO) after surgery. Poor prognosis exists for HOCM caused by PTPN11 mutation. Therefore, the aim of this study was to determine the clinical features of recurrent obstruction in children with HOCM caused by pathogenic mutations in the PTPN11 gene. METHODS: Fifty-six children who were diagnosed with HOCM underwent septal myectomies. Whole-exome sequencing of 49 pediatric cardiomyopathy-associated genes (including PTPN11) was performed. We performed hematoxylin-eosin, Masson, and wheat germ agglutinin staining of those tissues positive and negative for PTPN11. RESULTS: Whole-exome sequencing results showed 11 children with the PTPN11 mutation (19.6%). In long-term follow-up (median 37 months, maximum 9 years), children with the PTPN11 mutation had 6 (54.5%) recurrent LVOTOs compared with other groups (P = .015) but similar survival rates (P = .514). The mean postoperative time to recurrent obstruction was 22 ± 7 months. Children with PTPN11 mutation were 9-fold more likely to experience the risk associated with recurrent obstruction (95% confidence interval, 1.77-45.81, P < .001). Hematoxylin-eosin, Masson, and wheat germ agglutinin staining also revealed more cardiomyocyte hypertrophy in tissues with the PTPN11 mutation. CONCLUSIONS: Children with PTPN11 mutation-associated hypertrophic cardiomyopathy have a greater risk of recurrent LVOTO.

8.
Cells ; 13(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38920700

RESUMO

Cancer accounted for 10 million deaths in 2020, nearly one in every six deaths annually. Despite advancements, the contemporary clinical management of human neoplasms faces a number of challenges. Surgical removal of tumor tissues is often not possible technically, while radiation and chemotherapy pose the risk of damaging healthy cells, tissues, and organs, presenting complex clinical challenges. These require a paradigm shift in developing new therapeutic modalities moving towards a more personalized and targeted approach. The tumor-agnostic philosophy, one of these new modalities, focuses on characteristic molecular signatures of transformed cells independently of their traditional histopathological classification. These include commonly occurring DNA aberrations in cancer cells, shared metabolic features of their homeostasis or immune evasion measures of the tumor tissues. The first dedicated, FDA-approved tumor-agnostic agent's profound progression-free survival of 78% in mismatch repair-deficient colorectal cancer paved the way for the accelerated FDA approvals of novel tumor-agnostic therapeutic compounds. Here, we review the historical background, current status, and future perspectives of this new era of clinical oncology.


Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/genética , Neoplasias/patologia , Medicina de Precisão
9.
Int J Surg ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905490

RESUMO

OBJECTIVE: The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis. METHODS: We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors. RESULTS: 17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation (HR:5.634, 95%CI:1.663-19.086, P=0.005), Noonan syndrome (HR:3.770, 95%CI:1.245-11.419, P=0.019), preoperational systolic anterior motion (SAM)(HR:4.596, 95%CI:1.532-13.792, P=0.007)and mid-ventricular obstruction (HR:4.763, 95%CI:1.538-14.754, P=0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior (P=0.014), mid-inferoseptal(P=0.044), mid-inferior(P=0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis. CONCLUSION: Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.

10.
Virulence ; 15(1): 2368080, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38899573

RESUMO

Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.


Assuntos
Células Dendríticas , Vírus da Doença Hemorrágica de Coelhos , Limosilactobacillus reuteri , Peptídeos , Animais , Células Dendríticas/imunologia , Coelhos , Vírus da Doença Hemorrágica de Coelhos/imunologia , Vírus da Doença Hemorrágica de Coelhos/genética , Limosilactobacillus reuteri/genética , Limosilactobacillus reuteri/imunologia , Peptídeos/imunologia , Peptídeos/genética , Infecções por Caliciviridae/prevenção & controle , Infecções por Caliciviridae/imunologia , Infecções por Reoviridae/prevenção & controle , Infecções por Reoviridae/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Lactobacillus/genética , Lactobacillus/imunologia
11.
Medicine (Baltimore) ; 103(24): e38506, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875383

RESUMO

Blood cell ratios are a standard clinical index for the assessment of inflammation. Although a large number of epidemiological investigations have shown that inflammation is a potential risk factor for the development of coronary heart disease (CHD), there is not sufficient and direct evidence to confirm the relationship between blood cell ratios and CHD. Therefore, this study aimed to elucidate the effect of blood cell ratios on the incidence of coronary heart disease. This 10-year national study included data from 24,924 participants. The independent variable was blood cell ratios, and the dependent variable was coronary heart diseases (yes or no). The relationship between blood cell ratios and coronary heart disease was verified using baseline characteristic analysis, multivariate logistic regression analysis, smoothed fitted curves, and subgroup analysis. This study found that in multiple logistic regression analysis showed significant positive correlation between monocyte counts × meutrophil counts/lymphocyte counts (SIRI) (OR = 1.495; 95% CI = 1.154-1.938), monocyte-lymphocyte ratio (MLR) (OR = 3.081; 95% CI = 1.476-6.433) and the incidence of CHD; lymphocyte-monocyte ratio (LMR) (OR = 0.928;95% CI = 0.873-0.987), monocyte-lymphocyte ratio (PLR) (OR = 0.997;95% CI = 0.994-1.000) showed negative correlation with CHD. The smoothed curve fitting shows a nonlinear relationship between SIRI, LMR, PLR, and CHD, with an inverted U-shaped curve between SIRI and CHD, an L-shaped angle between LMR and CHD, and a U-shaped curve between PLR and CHD, respectively. Their inflection points are 1.462, 3.75, and 185.714, respectively. SIRI has an inverted U-shaped curve with coronary heart disease, suggesting that low levels of SIRI increase the risk of CHD; LMR with an L-shaped curve with CHD, and PLR with a U-shaped curve with CHD, suggesting that the risk of CHD can be prevented when LMR and PLR are reduced to a certain level. This has positive implications for the prevention and treatment of CHD.


Assuntos
Doença das Coronárias , Humanos , Masculino , Feminino , Doença das Coronárias/epidemiologia , Doença das Coronárias/sangue , Pessoa de Meia-Idade , Incidência , Adulto , Idoso , Monócitos , Fatores de Risco , Contagem de Linfócitos , Contagem de Leucócitos
12.
J Nanobiotechnology ; 22(1): 324, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858692

RESUMO

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.


Assuntos
Neoplasias da Mama , Glutationa , Nanopartículas , Espécies Reativas de Oxigênio , Dióxido de Silício , Neoplasias da Mama/tratamento farmacológico , Feminino , Nanopartículas/química , Animais , Glutationa/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Dióxido de Silício/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Xantonas/química , Xantonas/farmacologia , Taninos/química , Taninos/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Liberação Controlada de Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química
13.
Int J Biol Macromol ; 272(Pt 1): 132893, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38838883

RESUMO

Foodborne pathogens result in a great harm to human, which is an urgent problem to be addressed. Herein, a novel cellulose-based packaging films with excellent anti-bacterial properties under visible light were prepared. A porphyrin-based covalent organic polymer (Por-COPs) was constructed, then covalently grafted onto dialdehyde cellulose (DAC). The addition of Por-COPs enhanced the mechanical, hydrophobicity, and water resistance of the DAC-based composite films. DAC/Por-COP-2.5 film exhibited outstanding properties for the photodynamic inactivation of bacteria under visible light irradiation, delivering inactivation efficiencies of 99.90 % and 99.45 % towards Staphylococcus aureus and Escherichia coli within 20 min. The DAC/Por-COPs films efficiently generated •O2- and 1O2 under visible light, thereby causing oxidative stress to cell membranes for bacterial inactivation. The prepared composite film forms a protective barrier against bacterial contamination. Results guide the development of high performance and more sustainable packaging films for the food sector.


Assuntos
Celulose , Escherichia coli , Porfirinas , Staphylococcus aureus , Celulose/química , Celulose/análogos & derivados , Celulose/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Luz , Embalagem de Alimentos/métodos , Polímeros/química , Polímeros/farmacologia , Esterilização/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia
14.
Front Immunol ; 15: 1358036, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690262

RESUMO

Background: It remains unclear whether BPIV3 infection leads to stress granules formation and whether G3BP1 plays a role in this process and in viral replication. This study aims to clarify the association between BPIV3 and stress granules, explore the effect of G3BP1 on BPIV3 replication, and provide significant insights into the mechanisms by which BPIV3 evades the host's antiviral immunity to support its own survival. Methods: Here, we use Immunofluorescence staining to observe the effect of BPIV3 infection on the assembly of stress granules. Meanwhile, the expression changes of eIF2α and G3BP1 were determined. Overexpression or siRNA silencing of intracellular G3BP1 levels was examined for its regulatory control of BPIV3 replication. Results: We identify that the BPIV3 infection elicited phosphorylation of the eIF2α protein. However, it did not induce the assembly of stress granules; rather, it inhibited the formation of stress granules and downregulated the expression of G3BP1. G3BP1 overexpression facilitated the formation of stress granules within cells and hindered viral replication, while G3BP1 knockdown enhanced BPIV3 expression. Conclusion: This study suggest that G3BP1 plays a crucial role in BPIV3 suppressing stress granule formation and viral replication.


Assuntos
DNA Helicases , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , Replicação Viral , Animais , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , DNA Helicases/metabolismo , DNA Helicases/genética , RNA Helicases/metabolismo , RNA Helicases/genética , Grânulos de Estresse/metabolismo , Bovinos , Fator de Iniciação 2 em Eucariotos/metabolismo , Infecções por Respirovirus/imunologia , Infecções por Respirovirus/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Fosforilação , Linhagem Celular , Grânulos Citoplasmáticos/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2689-2698, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812169

RESUMO

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.


Assuntos
Neoplasias da Mama , Proliferação de Células , Emulsões , Verde de Indocianina , Humanos , Verde de Indocianina/química , Células MCF-7 , Emulsões/química , Proliferação de Células/efeitos dos fármacos , Feminino , Tamanho da Partícula , Géis/química , Nanopartículas/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Portadores de Fármacos/química
17.
J Agric Food Chem ; 72(15): 8859-8870, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564481

RESUMO

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.


Assuntos
Ácidos Graxos Monoinsaturados , Óleos de Peixe , Água , Triglicerídeos/química , Óleos de Peixe/química , Digestão
18.
J Med Virol ; 96(3): e29487, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38482901

RESUMO

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point-of-care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino-functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti-HuNoV monoclonal antibody was then conjugated with QDs-MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL-1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross-reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM-LFIC and RT-qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point-of-care testing in the future.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Rotavirus , Sapovirus , Humanos , Norovirus/genética , Microesferas , Rotavirus/genética , Sapovirus/genética , Fezes , Infecções por Caliciviridae/diagnóstico
19.
Nutrition ; 122: 112387, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38430844

RESUMO

OBJECTIVES: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes. METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients. RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients. CONCLUSION: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients' immunity status.


Assuntos
COVID-19 , Gastroenteropatias , Infecções por HIV , Humanos , Nutrição Enteral/métodos , Estudos Retrospectivos , Infecções por HIV/complicações , Pandemias , COVID-19/terapia , COVID-19/complicações , Unidades de Terapia Intensiva , Gastroenteropatias/etiologia , Biomarcadores , Estado Terminal/terapia
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