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1.
Sci Rep ; 14(1): 13943, 2024 06 17.
Article in English | MEDLINE | ID: mdl-38886539

ABSTRACT

Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM-receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P < 0.05). SPP1 and Collagen IV may be candidate biomarkers for type 2 diabetes mellitus combined with MASLD, as verified by bioinformatics screening and in vitro experiments. Our findings provide new targets for the treatment of type 2 diabetes combined with MASLD.


Subject(s)
Collagen Type IV , Diabetes Mellitus, Type 2 , Osteopontin , Protein Interaction Maps , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Animals , Rats , Collagen Type IV/genetics , Collagen Type IV/metabolism , Osteopontin/genetics , Osteopontin/metabolism , Gene Regulatory Networks , Disease Models, Animal , Computational Biology/methods , Gene Expression Profiling , Male , Humans , Gene Ontology , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/pathology , Signal Transduction
2.
Huan Jing Ke Xue ; 45(6): 3402-3411, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897761

ABSTRACT

Studies on the spatio-temporal variation and coordinated development level of compactness with carbon emission intensity in the Chengdu-Chongqing urban agglomeration is of great significance to achieve green, low-carbon, and high-quality development of society. The spatial-temporal differentiation, coupling coordination, and driving factors of the compactness and carbon emission intensity of the Chengdu-Chongqing urban agglomeration from 2010 to 2020 were analyzed by using the methods of comprehensive evaluation, carbon emission identical equality, coupling coordination, and the Geo-detector model. The results showed that:① The compactness of the Chengdu-Chongqing urban agglomeration continued to rise from 0.18 in 2010 to 0.22 in 2020, with an overall increase of 22.22 %, in which the contribution rate of economic compactness to urban compactness increased yearly. There were significant regional differences in the compactness of cities. The high-value areas were concentrated in Chengdu, Deyang, and Mianyang in the northwest and Zigong, Neijiang, and Luzhou in the southwest, whereas the low-value areas were distributed in the middle. Ya'an was always the area with the lowest compactness of urban agglomeration. ② The carbon emission intensity of the Chengdu-Chongqing urban agglomeration was decreasing yearly, with a decrease rate of 39.57 % during the study period. The carbon emission intensity in the southern part of the urban agglomeration was higher than that in other regions as a whole, whereas Chengdu and Chongqing were low-value areas all the year round, and the regional differences of carbon emission intensity were gradually narrowing. ③ The coupling degree between urban compactness and carbon emission intensity changed from the antagonistic stage to the running-in stage; the coupling coordination degree increased notably, from 0.21 in 2010 to 0.69 in 2020; and the two systems gradually moved towards benign and coordinated development. The coupling coordination between the northwest of the urban agglomeration (Chengdu, Deyang, and Mianyang) and the south of Sichuan (Zigong and Luzhou) was generally high. Industrial structure, scientific and technological innovation, urbanization level, government intervention, and environmental livability all had significant effects on the coupling and coordination of the two systems. ④ Optimizing industrial structure, strengthening scientific and technological support, improving the quality of urbanization development, implementing active policy guidance, and building green barriers were effective ways to promote the coordinated development of compactness and low carbon in the Chengdu-Chongqing urban agglomeration.

3.
Foods ; 13(12)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38928868

ABSTRACT

In our previous study, a new fermented food (PWF) created by utilizing pineapple by-products and whey proteins as a matrix via co-fermentation with lactic acid bacteria and yeast was developed, and, in the current study, we examined the impact of a pineapple-whey protein fermentation product on a cefixime-induced dysbiosis model in mice using 16S sequencing and untargeted metabolomics techniques. The results indicated that the pineapple-whey protein fermentation product played a positive role in restoring the intestinal flora. In this study, cefixime reduced the overall abundance of intestinal flora and decreased the relative abundance of probiotics in the gut, while also inhibiting amino acid metabolism. The addition of PWF normalized the intestinal flora to a steady state, significantly increasing the populations of Weissella, Lactococcus, Faecalibaculum, and Bacteroides acidophilus, while decreasing the numbers of Akkermansia and Escherichia-Shigella. Additionally, PWF modulated microbial metabolites, such as L-glutamate and L-threonine, and upregulated amino-acid-related metabolic pathways, including those involving glycine, serine, and threonine. In conclusion, PWF can alleviate intestinal flora dysbiosis and metabolic disturbances induced by antibiotic interventions. It is suggested that PWF could be a potential dietary strategy for patients with antibiotic-associated diarrhea.

4.
Food Res Int ; 186: 114367, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729727

ABSTRACT

Dry-cured hams contain abundant bioactive peptides with significant potential for the development of functional foods. However, the limited bioavailability of food-derived bioactive peptides has hindered their utilization in health food development. Moreover, there is insufficient regulatory information regarding bioactive peptides and related products globally. This review summarizes diverse bioactive peptides derived from dry-cured ham and by-products originating from various countries and regions. The bioactivity, preparation techniques, bioavailability, and metabolic stability of these bioactive peptides are described, as well as the legal and regulatory frameworks in various countries. The primary objectives of this review are to dig deeper into the functionality of dry-cured ham and provide theoretical support for the commercialization of bioactive peptides from food sources, especially the dry-cured ham.


Subject(s)
Food Handling , Meat Products , Peptides , Animals , Meat Products/analysis , Food Handling/methods , Biological Availability , Swine , Humans , Functional Food , Protein Stability
5.
Acta Pharmacol Sin ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698214

ABSTRACT

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

6.
BMJ Open Respir Res ; 11(1)2024 May 24.
Article in English | MEDLINE | ID: mdl-38789282

ABSTRACT

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Subject(s)
Pulmonary Disease, Chronic Obstructive , Spirometry , Humans , Male , Female , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Middle Aged , China/epidemiology , Aged , Forced Expiratory Volume , Vital Capacity , Smoking/epidemiology , Smoking/adverse effects , Lung/physiopathology , Prognosis
7.
N Engl J Med ; 390(17): 1584-1596, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38692292

ABSTRACT

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).


Subject(s)
ADAMTS13 Protein , Purpura, Thrombotic Thrombocytopenic , Recombinant Proteins , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , ADAMTS13 Protein/administration & dosage , ADAMTS13 Protein/adverse effects , ADAMTS13 Protein/deficiency , ADAMTS13 Protein/genetics , Cross-Over Studies , Purpura, Thrombotic Thrombocytopenic/congenital , Purpura, Thrombotic Thrombocytopenic/drug therapy , Purpura, Thrombotic Thrombocytopenic/genetics , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Child, Preschool
8.
Int J Mol Sci ; 25(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38791374

ABSTRACT

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 µM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.


Subject(s)
Antifungal Agents , Antimicrobial Peptides , Coleoptera , Cryptococcus neoformans , Microbial Sensitivity Tests , Cryptococcus neoformans/drug effects , Animals , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Coleoptera/microbiology , Coleoptera/drug effects , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Humans , Biofilms/drug effects , Amino Acid Sequence
9.
Zhen Ci Yan Jiu ; 49(4): 409-414, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38649210

ABSTRACT

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.


Subject(s)
Acupuncture Points , Blood Pressure , Hypertension , Transcutaneous Electric Nerve Stimulation , Humans , Hypertension/therapy , Hypertension/physiopathology
11.
J Nanobiotechnology ; 22(1): 193, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643134

ABSTRACT

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors.


Subject(s)
Neoplasms , Pyroptosis , Humans , Pyroptosis/physiology , Microbubbles , Neoplasms/drug therapy , Apoptosis , Hydralazine/pharmacology , Hydralazine/therapeutic use
12.
Front Immunol ; 15: 1356075, 2024.
Article in English | MEDLINE | ID: mdl-38529274

ABSTRACT

Background: During aging, chronic inflammation can promote tumor development and metastasis. Patients with chronic inflammatory bowel diseases (IBD) are at an increased risk of developing colorectal cancer (CRC). However, the molecular mechanism underlying is still unclear. Methods: We conducted a large-scale single-cell sequencing analysis comprising 432,314 single cells from 92 CRC and 24 IBD patients. The analysis focused on the heterogeneity and commonality of CRC and IBD with respect to immune cell landscape, cellular communication, aging and inflammatory response, and Meta programs. Results: The CRC and IBD had significantly different propensities in terms of cell proportions, differential genes and their functions, and cellular communication. The progression of CRC was mainly associated with epithelial cells, fibroblasts, and monocyte-macrophages, which displayed pronounced metabolic functions. In particular, monocyte-macrophages were enriched for the aging and inflammation-associated NF-κB pathway. And IBD was enriched in immune-related functions with B cells and T cells. Cellular communication analysis in CRC samples displayed an increase in MIF signaling from epithelial cells to T cells, and an increase in the efferent signal of senescence-associated SPP1 signaling from monocyte-macrophages. Notably, we also found some commonalities between CRC and IBD. The efferent and afferent signals showed that the pro-inflammatory cytokine played an important role. And the activity of aging and inflammatory response with AUCell analysis also showed a high degree of commonality. Furthermore, using the Meta programs (MPs) with the NMF algorithm, we found that the CRC non-malignant cells shared a substantial proportion of the MP genes with CRC malignant cells (68% overlap) and IBD epithelial cells (52% overlap), respectively. And it was extensively involved in functions of cell cycle and immune response, revealing its dual properties of inflammation and cancer. In addition, CRC malignant and non-malignant cells were enriched for the senescence-related cell cycle G2M phase transition and the p53 signaling pathway. Conclusion: Our study highlights the characteristics of aging, inflammation and tumor in CRC and IBD at the single-cell level, and the dual property of inflammation-cancer in CRC non-malignant cells may provide a more up-to-date understanding of disease transformation.


Subject(s)
Colorectal Neoplasms , Inflammatory Bowel Diseases , Humans , Transcriptome , Inflammation/genetics , Inflammation/complications , Cytokines , Tumor Microenvironment/genetics
13.
Lupus ; 33(6): 608-614, 2024 May.
Article in English | MEDLINE | ID: mdl-38518059

ABSTRACT

OBJECTIVE: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. METHODS: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. RESULTS: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). CONCLUSION: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.


Subject(s)
Antibodies, Monoclonal, Humanized , Lupus Erythematosus, Systemic , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Humans , Female , Young Adult , Adult , Middle Aged , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Retrospective Studies , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Treatment Outcome , Thrombocytopenia/drug therapy , Immunosuppressive Agents/adverse effects , Severity of Illness Index
14.
Anal Chem ; 96(14): 5437-5445, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38529794

ABSTRACT

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new meso-C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles. Interestingly, the meso-C═N-phenyl group-substituted probe 6 showed an obvious 594 nm fluorescence enhancement in glycerol and a moderate 650 nm red AIE emission in water. Further, on attaching CF3 to the phenyl group, a similar phenomenon was observed for 7 with red-shifted emissions, attributed to the introduction of a phenyl group, which plays a key role in the red AIE emissions and large Stokes shifts. Comparatively, for phenyl-group-free probes, both the meso-C═N-trifluoroethyl group and thiazole-substituted probes (8 and 9) exhibited good viscosity-responsive properties, while no AIE was observed due to the absence of phenyl groups. For cellular experiments, 6 and 9 showed good lysosomal and mitochondrial targeting properties, respectively, and were further successfully used for imaging viscosity through the preincubation of monensin and lipopolysaccharide (LPS), indicating that C═N polar groups potentially work as rotatable moieties and organelle-targeting groups, and the targeting difference might be ascribed to increased charges of thiazole. Therefore, in this study, we investigated the structural relationships of four meso-C═N BODIPY-based rotors with respect to their viscosity/AIE characteristics, subcellular-targeting ability, and cellular imaging for viscosity, potentially serving as AIE fluorescent probes with large Stokes shifts for subcellular viscosity imaging.


Subject(s)
Boron Compounds , Fluorescent Dyes , Organelles , Fluorescent Dyes/chemistry , Viscosity , Thiazoles
15.
Endocr Connect ; 13(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38552311

ABSTRACT

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

16.
Virol Sin ; 39(2): 309-318, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38458399

ABSTRACT

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.


Subject(s)
Bronchi , COVID-19 , Cell Degranulation , Mast Cells , SARS-CoV-2 , Trachea , Animals , Mast Cells/virology , Mast Cells/immunology , COVID-19/immunology , COVID-19/virology , COVID-19/pathology , Mice , Trachea/virology , Trachea/pathology , Bronchi/virology , Bronchi/pathology , Humans , Inflammation/virology , Epithelial Cells/virology , Disease Models, Animal
17.
Environ Pollut ; 348: 123811, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38531467

ABSTRACT

The relationship between long-term ozone (O3) exposure and readmission for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains elusive. In this study, we collected individual-level information on AECOPD hospitalizations from a standardized electronic database in Guangzhou from January 1, 2014, to December 31, 2015. We calculated the annual mean O3 concentration prior to the dates of the index hospitalization for AECOPD using patients' residential addresses. Employing Cox proportional hazards models, we assessed the association between long-term O3 concentration and the risk of AECOPD readmission across several time frames (30 days, 90 days, 180 days, and 365 days). We estimated the disease and economic burden of AECOPD readmissions attributable to O3 using a counterfactual approach. Of the 4574 patients included in the study, 1398 (30.6%) were readmitted during the study period, with 262 (5.7%) readmitted within 30 days. The annual mean O3 concentration was 90.3 µg/m3 (standard deviation [SD] = 8.2 µg/m3). A 10-µg/m3 increase in long-term O3 concentration resulted in a hazard ratio (HR) for AECOPD readmission within 30 days of 1.28 (95% confidence interval [CI], 1.09 to 1.49), with similar results for readmission within 90, 180, and 365 days. Older patients (aged 75 years or above) and males were more susceptible (HR, 1.33; 95% CI, 1.10-1.61 and HR, 1.29; 95% CI, 1.09-1.53, respectively). The population attributable fraction for 30-day readmission due to O3 exposure was 29.0% (95% CI, 28.4%-30.0%), and the attributable mean cost per participant was 362.3 USD (354.5-370.2). Long-term exposure to elevated O3 concentrations is associated with an increased risk of AECOPD readmission, contributing to a significant disease and economic burden.


Subject(s)
Ozone , Pulmonary Disease, Chronic Obstructive , Male , Humans , Patient Readmission , Pulmonary Disease, Chronic Obstructive/epidemiology , Hospitalization , Proportional Hazards Models , Retrospective Studies
18.
Food Chem ; 446: 138600, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38452500

ABSTRACT

An ethanol/(NH4)2SO4 biphasic (aqueous two-phase) system was designed to effectively separate antioxidant peptides from Xuanwei ham, and its potential to prevent ultraviolet A-induced damage to skin cells was explored. Optimization via single factor experiments and response surface methodology revealed that under 20 % ethanol aqueous solution (w/w), 25.5 % (NH4)2SO4 aqueous solution (w/w), and pH 8.80 conditions, the optimal extraction ratio was 59.0 ± 1.73 %. In vitro antioxidant activity and cellular assays showed that the peptide purified in the upper phase exhibited strong antioxidant activity, increasing the viability of HaCat cells damaged by UVA irradiation from 56.14 ± 1.05 % to 66.3 ± 1.76 %. We used an in silico peptide screening strategy and identified 10 with potential antioxidant activity, emphasizing the important role of amino acids Pro, Gly, and Ala in antioxidant activity.


Subject(s)
Antioxidants , Cytoprotection , Antioxidants/chemistry , Peptides/pharmacology , Peptides/chemistry , Water , Ethanol/chemistry
19.
Food Chem X ; 22: 101254, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38444559

ABSTRACT

In this study, a new fermented food was developed using pineapple by-products and whey protein (2.6%) as raw materials through the co-fermentation of autochthonous lactic acid bacteria and yeast. To better understand the fermentation mechanism and the impact of microorganisms on the entire fermentation system, we tracked the changes in carbohydrate and amino acid profiles, organoleptic quality and microbial community during the fermentation process. Compared with unfermented samples, dietary fiber and free amino acids increased significantly as fermentation proceeded. The fermented samples were significantly lower in astringency and bitterness and significantly higher in sourness, umami and richness. The fermented products were richer in volatile compounds with floral, cheesy, fruity and other flavors. Relevant analyses showed that the core microbial community was highly correlated with the quality attributes of the fermented products. Microorganisms such as Lactococcus, Weissella, Hanseniaspora, Saccharomyces and Lachancea contributed significantly to the fermented products.

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