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1.
Front Endocrinol (Lausanne) ; 15: 1309492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38757001

RESUMO

Objective: To investigate the relationship between dietary inflammatory index (DII) scores and infertility in US adults aged 18 to 45. Methods: Data were gathered from the 2013-2018 National Health and Nutrition Examination Survey (NHANES). In total, 3496 women were included in the study. To examine the relationship between DII, EDII and infertility, a weighted multivariable logistic regression analysis using continuous factors or categorical variables grouped by quartiles was conducted. Using subgroup analysis stratified based on DII and infertility features, the association between DII and infertility has been further studied. In order to determine whether there was a nonlinear relationship between DII and infertility, restricted cubic spline (RCS) analysis was carried out. Results: For statistical analysis, a total of 3496 individuals - 367 patients with infertility and 3129 persons without infertility - were included. A multivariable logistic regression study revealed a positive relationship between DII and infertility. A significant difference in subgroup analysis was shown in age group and race, although RCS analysis demonstrated nonlinear relationship between the DII and infertility. Conclusion: For participants aged 18-45 years, higher DII scores were positively correlated with infertility. In addition, anti-inflammatory diets might improve infertility outcomes.


Assuntos
Dieta , Infertilidade Feminina , Inflamação , Inquéritos Nutricionais , Humanos , Feminino , Adulto , Inflamação/epidemiologia , Adulto Jovem , Adolescente , Infertilidade Feminina/epidemiologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Estudos Transversais
2.
Cell Metab ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38703762

RESUMO

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

3.
J Agric Food Chem ; 72(10): 5237-5246, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427027

RESUMO

In this study, egg yolk selenium peptides (Se-EYP) were prepared using double-enzyme hydrolysis combined with a shearing pretreatment. The properties of the selenopeptides formed were then characterized, including their yield, composition, molecular weight distribution, antioxidant activity, in vitro digestion, and immunomodulatory activity. The peptide yield obtained after enzymatic hydrolysis using a combination of alkaline protease and neutral protease was 74.5%, of which 82.6% had a molecular weight <1000 Da. The selenium content of the lyophilized solid product was 4.01 µg/g. Chromatography-mass spectrometry analysis showed that 88.6% of selenium in Se-EYP was in the organic form, of which SeMet accounted for 60.3%, SeCys2 for 21.8%, and MeSeCys for 17.9%. After being exposed to in vitro simulated digestion, Se-EYP still had 65.1% of oligopeptides present, and the in vitro antioxidant activity was enhanced. Moreover, Se-EYP exhibited superior immune detection indices, including immune organ index, level of immune factors in the serum, histopathological changes in the spleen, and selenium content in the liver. Our results suggest that Se-EYP may be used as selenium-enriched ingredients in functional food products.


Assuntos
Selênio , Selênio/análise , Antioxidantes , Gema de Ovo/química , Peptídeos/química
4.
J Sci Food Agric ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441435

RESUMO

BACKGROUND: Salted hen egg yolks are less oily and less flavorful than salted duck egg yolks. However, hen eggs have a more adequate market supply and have a broader application prospect than duck eggs. In the present study, egg yolks, plasma, and granules were dehydrated by adding 1% NaCl to simulate traditional curing process of salted egg yolk. The changes in the pickling process of hen egg yolks (HEY) and duck egg yolks (DEY) plasma and granules were compared to reveal the gelation mechanism and the underlying causes of quality differences in salted HEY and DEY. Salted HEY can be compared with the changes in DEY during the pickling process to provide a theoretical basis for the quality improvement of salted HEY to salted DEY. RESULTS: The results showed that both plasma and granules were involved in gel formation, but exhibited different aggregation behaviors. Based on the intermolecular forces, the HEY proteins achieved aggregation mainly through hydrophobic interactions and DEY proteins mainly through covalent binding. According to spin-spin relaxation time, HEY gels immobilized a large amount of lipid and interacted strongly with lipids. DEY gels showed much free lipid and had weak interaction with lipid. The microstructure showed that HEY proteins were easily unfolded to form a homogeneous three-dimensional gel network structure after salting, whereas heterogeneous aggregates were formed to hinder the gel development in DEY. Changes in protein secondary structure content showed that pickling can promote the transformation of the α-helices to ß-sheets structure in HEY gels, whereas more α-helices structure was formed in DEY gels. CONCLUSION: The present study has demonstrated that different gelation behaviors of hen and duck egg yolk proteins (especially in plasma) through salting treatment led to the difference in the quality of salted HEY and DEY. © 2024 Society of Chemical Industry.

5.
Alzheimers Res Ther ; 16(1): 64, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528626

RESUMO

BACKGROUND: Posterior cortical atrophy (PCA) is a form of dementia that frequently displays significant visual dysfunction and relatively preserved cognitive and executive functions, thus hindering early diagnosis and treatment. This study aimed to investigate possible fundus markers in PCA patients and compare them with those of typical Alzheimer's disease (AD) patients to seek potential diagnostic patterns. METHODS: Age-matched PCA and AD patients and healthy controls (HC) completed optometry, intraocular pressure measurement, neuropsychologic assessments, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) examination in one visit. Overall, six outcomes of thicknesses of various retinal layers and seven outcomes of the retinal microvascular network were calculated. After adjusting for age, sex, and years of education, the OCT and OCTA results were analyzed using analysis of covariance and generalized linear models. Correlation analyses were performed using Spearman correlation, and ROC curves were plotted. RESULTS: Twelve PCA patients, nineteen AD patients, and thirty HC, aged 45-80 years were included. Fifty HC, thirty AD, and twenty PCA eyes were available for foveal avascular zone (FAZ) area analysis; forty-nine HC, thirty-four AD, and eighteen PCA eyes were available for OCT and OCTA assessments. PCA patients had thinner retinal nerve fiber layer and ganglion cell layer + inner plexiform layer than HC in the 0-3 mm circle and 1-3 mm ring. Few structural differences were observed between the AD group and the other two groups. The flow area of the superficial capillary plexus and the intermediate capillary plexus was smaller in the PCA group than in the HC group in the 0-1 mm circle, 0-3 mm circle. MMSE performed better than any combination of optical parameters in identifying AD and PCA from HC (AUC = 1), while the combination of MoCA, retinal thickness and vascular density of ICP in the 1-3 mm ring, with flow area of ICP in the 0-1 mm circle showed the strongest ability to distinguish PCA from AD (AUC = 0.944). CONCLUSIONS: PCA patients exhibited similar impairment patterns to AD patients in the fundus structure and microvascular network. OCTA may aid in the non-invasive detection of AD and PCA, but still remains to be substantiated.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/patologia , Tomografia de Coerência Óptica/métodos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Vasos Retinianos/fisiologia , Angiofluoresceinografia/métodos , Atrofia/patologia
6.
Chem Asian J ; 19(10): e202400190, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38451014

RESUMO

This work reports the cooperative reactivity of rare-earth aryloxide complexes with N-heterocyclic carbene (NHC) or N-heterocyclic olefin (NHO), showcasing their synergistic effect on the activation of H2 and diverse organic substrates. Reactions of RE(OAr)3 (RE=La, Sm, and Y; Ar=2,6-tBu2-C6H3) with unsaturated NHC ItBu (:C[N(R)CH]2, R=tBu) isolated abnormally bound RE metal NHC complexes RE/aNHC. In contrast, no metal-NHO adducts were formed when RE(OAr)3 were treated with NHO (R2C=C[N(R)C(R)]2, R=CH3). Both RE/aNHC and RE/NHO Lewis pairs enabled cooperative H2 activation. Furthermore, RE(OAr)3 were found to catalyze the hydrogenation of the exocyclic C=C double bond of NHO under mild conditions. Moreover, treatment of the La/aNHC complex with benzaldehyde produced a La/C4 1,2-addition product. The La/NHO Lewis pair could react with (trimethylsilyl)diazomethane and α, ß-conjugated imine, affording an isocyanotrimethylsilyl lanthanum amide complex and a La/C 1,4-addition product, respectively.

7.
Arthritis Rheumatol ; 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38403436

RESUMO

OBJECTIVE: The aim of this study was to describe the adult rheumatology workforce in the United States, assess change in rheumatology providers over time, and identify variation in rheumatology practice characteristics. METHODS: Using national Medicare claims data from 2006 to 2020, clinically active rheumatology physicians and advanced practice providers (APPs) were identified. Each calendar year was used for inclusion, exclusion, and analysis, and providers were determined to be entering, exiting, or stable based upon presence or absence in the prior or subsequent years of data. Characteristics (age, gender, practice type, rural, and region) of rheumatologists were determined for 2019 and in mutually exclusive study periods from 2009 to 2011, 2012 to 2015, and 2016 to 2019. The location of rheumatology practice was determined by billing tax identification and mapped. Demographics of physicians exiting or entering the rheumatology workforce were compared separately to those stable by logistic regression. RESULTS: The clinically active adult rheumatology workforce identified in US Medicare in 2019 was 5,667 rheumatologists and 379 APPs. From 2009 to 2020, the number of rheumatologists increased 23% and the number of APPs increased 141%. There was an increase in female rheumatologists over time, rising to 43% in 2019. Women and those employed by a health care system were more likely to exit, and those in a small practice or in the South were less likely to exit. CONCLUSION: The overall number of clinically active rheumatology providers grew more than 20% over the last decade to a high of 6,036 in 2020, although this rate of growth appears to be flattening off in later years.

9.
Heliyon ; 10(4): e26239, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420484

RESUMO

ChatGPT, an artificial intelligence (AI)-driven language model engineered by OpenAI, has experienced a substantial upsurge in adoption within higher education due to its versatile applications and sophisticated capabilities. Although prevailing research on ChatGPT has predominantly concentrated on its technological aspects and pedagogical ramifications, a comprehensive understanding of students' perceptions and experiences regarding ChatGPT remains elusive. To address this gap, this study employed a peer interview methodology, conducting a thematic analysis of 106 first-year undergraduates and 81 first-year postgraduate students' perceptions from diverse disciplines at a comprehensive university in East China. The data analysis revealed that among the four factors examined-grade, age, gender, and major-grade emerged as the most influential determinant, followed by age and major. Postgraduate students demonstrated heightened awareness of the potential limitations of ChatGPT in addressing academic challenges and exhibited greater concern for security issues associated with its application. This research offers essential insights into students' perceptions and experiences with ChatGPT, emphasizing the importance of recognizing potential limitations and ethical concerns associated with ChatGPT usage. Additionally, the findings highlight ethical concerns, as students noted the importance of responsible data handling and academic integrity in ChatGPT usage, underscoring the need for ethical guidance in AI utilization. Moreover, further research is essential to optimize AI use in education, aiming to improve learning outcomes effectively.

10.
Int J Biol Macromol ; 259(Pt 2): 129298, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199555

RESUMO

Seeking safe and environmentally friendly natural immunomodulators is a pressing requirement of humanity. This study investigated the differential binding characteristics of two polar polyphenols (PP), namely epicatechin (EC) and chlorogenic acid (CA), to ovotransferrin (OVT), and explored the relationship between structural transformations and immunomodulatory activity of OVT-PP complexes. Results showed that CA exhibited a stronger affinity for OVT than EC, mainly driven by hydrogen bonds and van der Waals forces. Complexation-induced conformational variations in OVT, including static fluorescence quenching, increased microenvironment polarity surrounding tryptophan and tyrosine residues, and the transition from disordered α-helix to stable ß-sheet. Furthermore, the structural conformation transformation of OVT-PP complexes facilitated the enhancement of immunomodulatory activity, with the OVT-CA (10:2) complex demonstrating the best immunomodulatory activity. Principal component analysis (PCA) and Pearson correlation analysis revealed the immunomodulatory activities of the OVT-PP complexes were influenced by surface hydrophobicity (negatively correlated), ß-sheet percentage and polyphenol binding constants. It could be inferred that PP complexation increased the surface polarity of OVT, consequently enhancing its immunomodulatory activity by promoting cell membrane affinity and antigen recognition. This study provides valuable guidance for effectively utilizing polyphenol-protein complexes in enhancing immunomodulatory activity.


Assuntos
Catequina , Conalbumina , Ácido Clorogênico , Fatores Imunológicos/farmacologia , Polifenóis/farmacologia
11.
Brain Sci ; 14(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275525

RESUMO

Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutamatergic projections from the infralimbic cortex (IL) to the ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 min, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 h post-stimulation, persisting up to 16-24 h. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS's sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS's effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy.

12.
Arthritis Care Res (Hoboken) ; 76(4): 550-558, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37909385

RESUMO

OBJECTIVE: The objective of this study was to determine the proportion of new medication prescriptions observed in electronic health records (EHR) that represent true incident medication use, accounting for undocumented previous prescriptions (prevalent medication use) and failure to initiate treatment (primary nonadherence) with linked administrative claims data as the reference standard. METHODS: Using single-specialty rheumatology EHR data from more than 700 community practices in the United States linked to administrative claims data, we identified first (index) EHR prescriptions and assessed the positive predictive value (PPV) of different EHR-derived new user definitions to identify true incident use (no prior claims). We then assessed how often index EHR prescriptions that met a definition of new use resulted in primary nonadherence (no subsequent claims). RESULTS: Overall, 12,405 index EHR prescriptions were identified with PPVs of 0.59 to 0.67 for true incident use. PPVs increased to 0.76 to 0.85 by excluding medications listed during the EHR medication reconciliation process and further increased to 0.87 to 0.93 by requiring ≥12 elapsed months since the first rheumatology office visit. Primary nonadherence at three months was observed in 33% to 38% overall and varied substantially by medication class, ranging from 15% to 23% for conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to 54% to 64% for targeted synthetic DMARDs. CONCLUSION: New DMARD use was accurately distinguished from prevalent use with EHR prescriptions and simple new user definitions that include current medications collected during medication reconciliation. Primary nonadherence was frequent and varied by DMARD class. This has important implications for epidemiologic studies using EHR data and for optimal delivery of clinical care.


Assuntos
Antirreumáticos , Reumatologia , Humanos , Estados Unidos , Estudos Retrospectivos , Registros Eletrônicos de Saúde , Prescrições de Medicamentos , Antirreumáticos/uso terapêutico , Adesão à Medicação
13.
J Sci Food Agric ; 104(5): 2621-2629, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37985210

RESUMO

BACKGROUND: The uses of egg white powder (EWP) are restricted because of its odor. It is necessary to find a method to improve its flavor. In this paper, three different antioxidants - green tea extract (GTE), sodium ascorbate (SA), and glutathione (GSH) - were selected to modify the flavor. The physicochemical and structural properties of EWP were investigated to study the mechanism of the formation and release of volatile compounds. RESULTS: Antioxidants can modify the overall flavor of EWP significantly, inhibiting the generation or release of nonanal, 3-methylbutanal, heptanal, decanal, geranyl acetone, and 2-pemtylfuran. A SA-EWP combination showed the lowest concentration of 'off' flavor compounds; GTE-EWP and GSH-EWP could reduce several 'off' flavor compounds but increased the formation of geranyl acetone and furans. The changes in the carbonyl content and the amino acid composition confirmed the inhibition of antioxidants with the oxidative degradation of proteins or characteristic amino acids. The results of fluorescence spectroscopy and Fourier transform infrared (FTIR) spectroscopy provided structural information regarding EWP, which showed the release of volatile compounds decreased due to structural changes. For example, the surface hydrophobicity increased and the protein aggregation state changed. CONCLUSIONS: Antioxidants reduce the 'off' flavor of EWP in two ways: they inhibit protein oxidation and Maillard reactions (they inhibit formation of 3-methylbutanal and 2-pemtylfuran) and they enhance the binding ability of heat-denatured proteins (reducing the release of nonanal, decanal, and similar compounds). © 2023 Society of Chemical Industry.


Assuntos
Aldeídos , Antioxidantes , Clara de Ovo , Terpenos , Antioxidantes/química , Clara de Ovo/química , Pós , Aminoácidos
14.
Food Funct ; 15(1): 401-410, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38099483

RESUMO

Fish collagen, derived from sustainable sources, offers a valuable substrate for generating peptides with diverse biofunctionalities. In this study, alkaline, papain, and ginger protease were used to enzymatically hydrolyze fish skin collagen. The peptide molecular weight distribution and sequence were measured using HPLC and ICP-MS-MS, with papain/alkaline protease (AP) and papain/alkaline/ginger protease (APG) hydrolyzed samples compared. As the results showed, the incorporation of ginger protease was useful for increasing the degree of hydrolysis, with the content of <400 Da peptides increasing from 49.82% to 58.56%. The identified peptide sequence in the APG sample had more proline at the C-terminal. The peptides were separated into two components (different in molecular weight) using gel column chromatography. The molecular weight distribution, amino acid composition, ACE inhibitory activity, and fibroblast proliferation activity of the collected components were measured. In comparison, the contents of proline and hydroxyproline in the larger peptides decreased obviously after combined hydrolysis by ginger protease, reflecting the formation of a peptide sequence of smaller molecular weight containing glycine and hydroxyproline. The combined hydrolysis of ginger protease was beneficial for the improvement of the ACE inhibitory activity of the sample. However, the fibroblast proliferation activity of AP was higher than that of APG, indicating that further hydrolysis by ginger protease may destroy the hydroxyproline at the end of the peptide sequence. This study proposed a creative directional hydrolysis method and provided practical guidance for the production of collagen peptides with enhanced functional activity.


Assuntos
Papaína , Peptídeos , Animais , Hidrólise , Hidroxiprolina , Papaína/metabolismo , Peptídeos/química , Colágeno/metabolismo , Prolina , Relação Estrutura-Atividade
15.
Gels ; 9(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38131927

RESUMO

Plant essential oil has attracted much attention in delaying pork spoilage due to its safety, but its low antibacterial efficiency needs to be solved by encapsulation. Our previous research had fabricated a type of ovalbumin gel nanoparticles loaded with carvacrol (OCGn-2) using the gel-embedding method, which had a high encapsulation rate and antibacterial activity. The main purpose of this study was to further evaluate the stability and slow-release characteristics of OCGn-2 and potential quality effects of the nanoparticles on the preservation of fresh pork pieces during 4 °C storage. The particle test showed that the nanoparticles had better heat stability below 85 °C and salt stability below 90 mM. The in vitro release study indicated that the carvacrol in OCGn-2 followed a Fickian release mechanism. The pork preservation test suggested that the OCGn-2 coating treatments could remarkably restrict the quality decay of pork slices compared to free carvacrol or a physical mixture of ovalbumin and carvacrol treatment. Nano-encapsulation of ovalbumin is beneficial to the sustained release, enhanced oxidation resistance, and improved antibacterial activity of carvacrol. The study suggested that ovalbumin gel nanoparticles embedded with carvacrol could be applied as an efficient bacterial active packaging to extend the storage life of pork.

16.
Front Bioeng Biotechnol ; 11: 1227327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929198

RESUMO

The limited portability of pneumatic pumps presents a challenge for ankle-foot orthosis actuated by pneumatic actuators. The high-pressure requirements and time delay responses of pneumatic actuators necessitate a powerful and large pump, which renders the entire device heavy and inconvenient to carry. In this paper, we propose and validate a concept that enhances portability by employing a slack cable tendon mechanism. By managing slack tension properly, the time delay response problem of pneumatic actuators is eliminated through early triggering, and the system can be effectively controlled to generate the desired force for dorsiflexion assistance. The current portable integration of the system weighs approximately 1.6 kg, with distribution of 0.5 kg actuation part on the shank and 1.1 kg power system on the waist, excluding the battery. A mathematical model is developed to determine the proper triggering time and volumetric flow rate requirements for pump selection. To evaluate the performance of this actuation system and mathematical model, the artificial muscle's response time and real volumetric flow rate were preliminarily tested with different portable pumps on a healthy participant during treadmill walking at various speeds ranging from 0.5 m/s to 1.75 m/s. Two small pumps, specifically VN-C1 (5.36 L/min, 300 g) and VN-C4 (9.71L/min, 550 g), meet our design criteria, and then tested on three healthy subjects walking at normal speeds of 1 m/s and 1.5 m/s. The kinematic and electromyographic results demonstrate that the device can facilitate ankle dorsiflexion with a portable pump (300-500 g), generating sufficient force to lift up the foot segment, and reducing muscle activity responsible for ankle dorsiflexion during the swing phase by 8% and 10% at normal speeds of 1 m/s and 1.5 m/s respectively. This portable ankle robot, equipped with a compact pump weighing approximately 1.6 kg, holds significant potential for assisting individuals with lower limb weakness in walking, both within their homes and in clinical settings.

17.
Int J Mol Sci ; 24(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37762527

RESUMO

Alzheimer's disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 (p = 0.004), 0.833 (p = 0.008), and 0.783 (p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 (p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD.


Assuntos
Doença de Alzheimer , Idoso , Humanos , Doença de Alzheimer/diagnóstico , Proteômica , Adenosina Trifosfatases , Área Sob a Curva , Biomarcadores
18.
ACS Nano ; 17(16): 15542-15555, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37577982

RESUMO

The efficient delivery of anticancer agents into tumor microenvironments is critical for the success of cancer therapies, but it is a prerequisite that drug carriers should overcome tumor vasculature and possess high drug contents. Here, we found that photoinduced inflammation response caused the migration of neutrophils into tumor microenvironments and neutrophils transported neutrophil-targeted nanoparticles (NPs) across the tumor blood barrier. The results showed that tumor delivery efficiencies of NPs were 5% ID/g, and they were independent of particle sizes (30-200 nm) and their doses (108-1011 NPs). To efficiently deliver anticancer agents into tumors via neutrophils, we fabricated carrier-free paclitaxel nanocrystals (PTX NC). The results showed that neutrophil uptake of PTX NC did not impair neutrophil tumor infiltration, and the sustainable release of PTX from PTX NC in tumors was regulated by paclitaxel protein complexes, thus improving the mouse survival in two preclinical models. Our studies demonstrate that delivery of nanocrystal drugs via neutrophils is a promising method to effectively treat a wide range of cancers, and we have also identified a mechanism of drug release from neutrophils in tumors.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Animais , Camundongos , Neutrófilos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Antineoplásicos/química , Portadores de Fármacos/química , Neoplasias/tratamento farmacológico , Inflamação/tratamento farmacológico , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral
19.
Methods Mol Biol ; 2712: 117-133, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37578701

RESUMO

Ferroptosis is a unique form of iron-dependent cell death induced by lipid peroxidation and subsequent plasma membrane rupture, which sets it apart from other types of regulated cell death. Ferroptosis has been linked to a diverse range of biological processes, such as aging, immunity, and cancer. Organoids, on the other hand, are three-dimensional (3D) miniaturized model systems of different organs in vitro cultures, which have gained widespread interest for modeling tissue development and disease, drug screening, and cell therapy. Organoids offer tremendous potential for improving our understanding of human diseases, particularly in the search for the field of ferroptosis in pathological processes of organs. Furthermore, cancer organoids are utilized to investigate molecular mechanisms and drug screening in vitro due to the anti-tumor effect of ferroptosis. Currently, the development of liver organoids has reached a relatively mature stage. Here, we present the protocols for the generation of liver organoids and liver cancer organoids, along with the methods for detecting ferroptosis in organoids.


Assuntos
Ferroptose , Neoplasias Hepáticas , Humanos , Morte Celular/fisiologia , Ferro/metabolismo , Peroxidação de Lipídeos , Organoides , Neoplasias Hepáticas/metabolismo
20.
J Sci Food Agric ; 103(14): 7127-7135, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37380626

RESUMO

BACKGROUND: Ovalbumin (OVA), accounting for 50% of proteins in egg white, is a kind of high-quality protein with excellent nutritional and processing functions. Acid heat treatment will induce the deformation and filtration of OVA, endowing it with improved functionality. However, the molecular kinetic process during the fibrillation of OVA and the application of the fabricated OVA fibrils (OVAFs) have not been thoroughly studied and revealed. RESULTS: In this study, the fabrication mechanism and the application OVAFs as an interfacial stabilizer and polyphenol protector were investigated. Acidic (pH 3.0) heat treatment was used to induce the fibrillation of OVA, and thioflavin T fluorescence intensity, molecular weight distribution, and the tertiary and secondary structures of OVAF samples were recorded to determine the fibrillation efficiency and the molecular mechanism. The results showed that, in the initial stage of fibrillation, OVA first hydrolyzed to oligopeptides, accompanied by the exposure of hydrophobic domains. Then, oligopeptides were connected by disulfide bonds to form primary fibril monomers. Hydrophobic interaction and hydrogen bonding may participate in the further polymerization of the fibrils. The fabricated OVAFs were characterized by a ß-sheet-rich structure and possessed improved emulsifying, foaming, and polyphenol protection ability. CONCLUSION: The research work was meaningful for exploring the application of globular water-soluble OVA in an emerging nutritious food with novel texture and sensory properties. © 2023 Society of Chemical Industry.


Assuntos
Clara de Ovo , Temperatura Alta , Ovalbumina/química , Clara de Ovo/química , Oligopeptídeos , Polifenóis
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