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1.
Nat Commun ; 15(1): 4085, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744837

RESUMEN

Global riverine nitrous oxide (N2O) emissions have increased more than 4-fold in the last century. It has been estimated that the hyporheic zones in small streams alone may contribute approximately 85% of these N2O emissions. However, the mechanisms and pathways controlling hyporheic N2O production in stream ecosystems remain unknown. Here, we report that ammonia-derived pathways, rather than the nitrate-derived pathways, are the dominant hyporheic N2O sources (69.6 ± 2.1%) in agricultural streams around the world. The N2O fluxes are mainly in positive correlation with ammonia. The potential N2O metabolic pathways of metagenome-assembled genomes (MAGs) provides evidence that nitrifying bacteria contain greater abundances of N2O production-related genes than denitrifying bacteria. Taken together, this study highlights the importance of mitigating agriculturally derived ammonium in low-order agricultural streams in controlling N2O emissions. Global models of riverine ecosystems need to better represent ammonia-derived pathways for accurately estimating and predicting riverine N2O emissions.


Asunto(s)
Amoníaco , Compuestos de Amonio , Bacterias , Ecosistema , Óxido Nitroso , Ríos , Óxido Nitroso/metabolismo , Ríos/microbiología , Ríos/química , Compuestos de Amonio/metabolismo , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación , Amoníaco/metabolismo , Metagenoma , Agricultura , Nitratos/metabolismo , Desnitrificación , Nitrificación , Redes y Vías Metabólicas/genética
2.
Front Pharmacol ; 15: 1390294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720773

RESUMEN

Introduction: Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer's disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats. Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot. Results: Treatment with 720 mg/kg RGLS for 14 days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN). Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.

3.
Front Pharmacol ; 15: 1406127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720779

RESUMEN

Introduction: Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer's disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer's disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear. Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test. Results: Behavioral tests demonstrated that RGLS (360 and 720 mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC. Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38668959

RESUMEN

PURPOSE: This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion. METHODS: Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion. RESULTS: Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC. CONCLUSION: We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.

5.
Front Immunol ; 15: 1376544, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638440

RESUMEN

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort. Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness. Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models. Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.


Asunto(s)
Enfermedades Cardiovasculares , Sarcopenia , Adulto , Anciano , Humanos , Causas de Muerte , Encuestas Nutricionales , Inflamación
6.
World J Gastroenterol ; 30(11): 1588-1608, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38617450

RESUMEN

BACKGROUND: Acute liver failure (ALF) has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis. The silent information regulator sirtuin 1 (SIRT1)-mediated deacetylation affects multiple biological processes, including cellular senescence, apoptosis, sugar and lipid metabolism, oxidative stress, and inflammation. AIM: To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms. METHODS: This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) testing. C57BL/6 mice were also intraperitoneally pretreated with SIRT1, p53, or glutathione peroxidase 4 (GPX4) inducers and inhibitors and injected with lipopolysaccharide (LPS)/D-galactosamine (D-GalN) to induce ALF. Gasdermin D (GSDMD)-/- mice were used as an experimental group. Histological changes in liver tissue were monitored by hematoxylin and eosin staining. ALT, AST, glutathione, reactive oxygen species, and iron levels were measured using commercial kits. Ferroptosis- and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction. SIRT1, p53, and GSDMD were assessed by immunofluorescence analysis. RESULTS: Serum AST and ALT levels were elevated in patients with ALF. SIRT1, solute carrier family 7a member 11 (SLC7A11), and GPX4 protein expression was decreased and acetylated p5, p53, GSDMD, and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein levels were elevated in human ALF liver tissue. In the p53 and ferroptosis inhibitor-treated and GSDMD-/- groups, serum interleukin (IL)-1ß, tumour necrosis factor alpha, IL-6, IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated. In mice with GSDMD knockout, p53 was reduced, GPX4 was increased, and ferroptotic events (depletion of SLC7A11, elevation of ACSL4, and iron accumulation) were detected. In vitro, knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels, the cytostatic rate, and GSDMD expression, restoring SLC7A11 depletion. Moreover, SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group, accompanied by reduced p53, GSDMD, and ACSL4, and increased SLC7A11 and GPX4. Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalN-induced in vitro and in vivo models. CONCLUSION: SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.


Asunto(s)
Fallo Hepático Agudo , Sirtuina 1 , Animales , Humanos , Ratones , Gasderminas , Hierro , Lipopolisacáridos , Fallo Hepático Agudo/inducido químicamente , Ratones Endogámicos C57BL , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Sirtuina 1/genética , Proteína p53 Supresora de Tumor
7.
Heliyon ; 10(7): e29020, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38617917

RESUMEN

Purpose: This study aimed to systematically evaluate the quality of content and information in videos related to gestational diabetes mellitus on Chinese social media platforms. Methods: The videos on various platforms, TikTok, Bilibili, and Weibo, were searched with the keyword "gestational diabetes mellitus" in Chinese, and the first 50 videos with a comprehensive ranking on each platform were included for subsequent analysis. Characteristic information of video was collected, such as their duration, number of days online, number of likes, comments, and number of shares. DISCREN, JAMA (The Journal of the American Medical Association) Benchmark Criteria, and GQS (Global Quality Scores) were used to assess the quality of all videos. Finally, the correlation analysis was performed among video features, video sources, DISCERN scores, and JAMA scores. Results: Ultimately, 135 videos were included in this study. The mean DISCERN total score was 31.84 ± 7.85, the mean JAMA score was 2.33 ± 0.72, and the mean GQS was 2.00 ± 0.40. Most of the videos (52.6%) were uploaded by independent medical professionals, and videos uploaded by professionals had the shortest duration and time online (P < 0.001). The source of the video was associated with numbers of "likes", "comments", and "shares" for JAMA scores (P < 0.001), but there was no correlation with DISCERN scores. Generally, videos on TikTok with the shortest duration received the most numbers of "likes", "comments", and "shares", but the overall quality of videos on Weibo was higher. Conclusion: Although the majority of the videos were uploaded by independent medical professionals, the overall quality appeared to be poor. Therefore, more efforts and actions should be taken to improve the quality of videos related to gestational diabetes mellitus.

8.
J Vis Exp ; (205)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38619279

RESUMEN

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.


Asunto(s)
Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Ácidos Nucleicos , Infecciones del Sistema Respiratorio , Humanos , Microfluídica , Reproducibilidad de los Resultados , Infecciones del Sistema Respiratorio/diagnóstico , Klebsiella pneumoniae
9.
Mater Horiz ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38629215

RESUMEN

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

10.
Front Neurosci ; 18: 1309684, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576865

RESUMEN

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

11.
J Sci Food Agric ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38655901

RESUMEN

BACKGROUND: Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI-polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI-inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined. RESULTS: In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), new C-N bonds were formed in Fourier-transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h. CONCLUSION: This study revealed that WPI-inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry.

12.
Diabetes Obes Metab ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38685601

RESUMEN

AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38687387

RESUMEN

Eicosapentaenoic acid (EPA) is a vital É·-3 polyunsaturated fatty acid (PUFA) for human body with various physiological functions. In this study, we proposed an adaptive evolutionary strategy based on high-temperature and high-oxygen two-factor stress to increase the EPA production capacity of Schizochytrium. High-temperature stress was used to increase EPA yield, and high oxygen was implemented to continuously stimulate cell growth and lipid accumulation. The biomass and EPA production of ALE-D50 reached 35.33 g/L and 1.54 g/L, which were 43.85% and 71.11% higher than that of the original strain, respectively. Lower in vivo reactive oxygen species levels indicated that the evolved strain possessed stronger antioxidant activity. Liquid chromatography-mass spectrometry metabolomics showed that enhanced glucose consumption and glycolysis metabolism, as well as a weakened tricarboxylic acid cycle and reduced amino acid metabolic tributaries in the evolved strain, might be associated with increased growth and EPA synthesis. Finally, the lipid production and EPA production in a fed-batch fermentation were further increased to 48.93 g/L and 3.55 g/L, improving by 54.30% and 90.86%, respectively. This study provides a novel pathway for promoting EPA biosynthesis in Schizochytrium.

16.
Nat Commun ; 15(1): 3131, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605012

RESUMEN

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.


Asunto(s)
Osteogénesis , Andamios del Tejido , Osteogénesis/fisiología , Andamios del Tejido/química , Porosidad , Impresión Tridimensional , Zinc/farmacología
17.
ACS Appl Mater Interfaces ; 16(12): 14434-14444, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38498684

RESUMEN

Natural compounds like pterostilbene (PTE) have gained recognition for their various biological activities and potential health benefits. However, challenges related to bioavailability and limited clinical efficacy have prompted efforts to strengthen their therapeutic potential. To meet these challenges, we herein rationally designed and successfully synthesized a pharmaceutical phosphoramidite that allows for the programmable incorporation of PTE into oligonucleotides. The resultant aptamer-PTE conjugate can selectively bind to cancer cells, leading to a specific internalization and drug release. Moreover, compared with free PTE, the conjugate exhibits superior cytotoxicity in cancer cells. Specifically, in a zebrafish xenograft model, the nanomedicine effectively inhibits tumor growth and neovascularization, highlighting its potential for targeted antitumor therapy. This approach presents a promising avenue for harnessing the therapeutic potential of natural compounds via a nanomedicine solution.


Asunto(s)
Nanomedicina , Neoplasias , Animales , Humanos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Oligonucleótidos , Pez Cebra
18.
J Virol ; 98(4): e0013924, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38501663

RESUMEN

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus, and the broad interspecies infection of SADS-CoV poses a potential threat to human health. This study provides experimental evidence to dissect the roles of distinct domains within the SADS-CoV spike S1 subunit in cellular entry. Specifically, we expressed the S1 and its subdomains, S1A and S1B. Cell binding and invasion inhibition assays revealed a preference for the S1B subdomain in binding to the receptors on the cell surface, and this unknown receptor is not utilized by the porcine epidemic diarrhea virus. Nanoparticle display demonstrated hemagglutination of erythrocytes from pigs, humans, and mice, linking the S1A subdomain to the binding of sialic acid (Sia) involved in virus attachment. We successfully rescued GFP-labeled SADS-CoV (rSADS-GFP) from a recombinant cDNA clone to track viral infection. Antisera raised against S1, S1A, or S1B contained highly potent neutralizing antibodies, with anti-S1B showing better efficiency in neutralizing rSADS-GFP infection compared to anti-S1A. Furthermore, depletion of heparan sulfate (HS) by heparinase treatment or pre-incubation of rSADS-GFP with HS or constituent monosaccharides could inhibit SADS-CoV entry. Finally, we demonstrated that active furin cleavage of S glycoprotein and the presence of type II transmembrane serine protease (TMPRSS2) are essential for SADS-CoV infection. These combined observations suggest that the wide cell tropism of SADS-CoV may be related to the distribution of Sia or HS on the cell surface, whereas the S1B contains the main protein receptor binding site. Specific host proteases also play important roles in facilitating SADS-CoV entry.IMPORTANCESwine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel pathogen infecting piglet, and its unique genetic evolution characteristics and broad species tropism suggest the potential for cross-species transmission. The virus enters cells through its spike (S) glycoprotein. In this study, we identify the receptor binding domain on the C-terminal part of the S1 subunit (S1B) of SADS-CoV, whereas the sugar-binding domain located at the S1 N-terminal part of S1 (S1A). Sialic acid, heparan sulfate, and specific host proteases play essential roles in viral attachment and entry. The dissection of SADS-CoV S1 subunit's functional domains and identification of cellular entry cofactors will help to explore the receptors used by SADS-CoV, which may contribute to exploring the mechanisms behind cross-species transmission and host tropism.


Asunto(s)
Alphacoronavirus , Infecciones por Coronavirus , Glicoproteína de la Espiga del Coronavirus , Animales , Humanos , Ratones , Alphacoronavirus/química , Alphacoronavirus/fisiología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Heparitina Sulfato , Ácido N-Acetilneuramínico/metabolismo , Péptido Hidrolasas , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Porcinos
19.
Food Chem X ; 22: 101257, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38495458

RESUMEN

In this study, high-throughput sequencing and metabolomics analysis were conducted to analyze the microbial and metabolites of dry-cured Sanchuan ham, Laowo ham, Nuodeng ham, and Heqing ham that have fermented for two years produced from western Yunnan China. Results showed that at the genus level, the dominant bacteria in the four types of ham were Halomonas and Staphylococcus, while the dominant fungi were Aspergillus and Yamadazyma. A total 422 different metabolites were identified in four types of ham, mainly amino acids, peptides, fatty acids, and their structural analogs, which were involved in pantothenate and coenzyme A biosynthesis, caffeine, and tyrosine metabolism. The dominant microorganisms of the four types of ham were mainly related to the metabolism of fatty acids and amino acids. This research enhances the identification degree of these four types of dry-cured ham and provides a theoretical basis for developing innovative and distinctive ham products.

20.
Diabetol Metab Syndr ; 16(1): 57, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429774

RESUMEN

PURPOSE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP. METHODS: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group. RESULTS: Baseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population. CONCLUSIONS: ICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.

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