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1.
PLoS One ; 19(6): e0304325, 2024.
Article in English | MEDLINE | ID: mdl-38833445

ABSTRACT

BACKGROUND: Stroke patients with dysphagia and family caregivers will experience multiple transitions during the whole process of the disease and various nursing needs will be generated. There is a lack of knowledge about their experiences at different transition stages. Thus, we aimed to explore the transition experiences of patients with post stroke dysphagia and family caregivers from admission to discharge home. METHODS: A semi-structured interview based on Meleis's transition theory was used during hospitalization and telephone follow-up interviews were conducted in the first, third, and sixth month after the diagnosis of dysphagia. Interview transcripts were analyzed using the conventional content analysis method. RESULTS: A total of 17 participants enrolled in the first face-to-face interview, 16 participants took part in the first month's telephone follow-up interview, 14 participants in the third month, and 12 participants in the sixth month. The transition experiences of patients with post stroke dysphagia and family caregivers could be summarized into three themes: (1)transition from onset to admission; (2)transition from discharge to other rehabilitation institutions; and (3)transition from discharge to home. Each theme had identified interrelated subthemes. CONCLUSIONS: The experiences of patients with post stroke dysphagia and family caregivers during transition are a dynamic process with enormous challenges in each phase. Collaboration with health care professionals, follow-up support after discharge, and available community and social support should be integrated into transitional nursing to help patients facilitate their transition.


Subject(s)
Caregivers , Deglutition Disorders , Qualitative Research , Stroke , Humans , Deglutition Disorders/psychology , Male , Female , Caregivers/psychology , Stroke/psychology , Stroke/complications , Aged , Middle Aged , Longitudinal Studies , Patient Discharge , Stroke Rehabilitation , Aged, 80 and over , Adult
2.
Angew Chem Int Ed Engl ; : e202407125, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828628

ABSTRACT

Trees grow by coupling the transpiration-induced nutrient absorption from external sources and photosynthesis-based nutrient integration. Inspired by this manner, we designed a class of polyion complex (PIC) hydrogels containing isolated liquid-filled voids for growing texture surfaces. The isolated liquid-filled voids were created via irreversible matrix reconfiguration in a deswelling-swelling process. During transpiration, these voids reversibly collapse to generate negative pressures within the matrices to extract polymerizable compounds from external sources and deliver them to the surface of the samples for photopolymerization. This growth process is spatial-controllable and can be applied to fabricate complex patterns consisting of different compositions, suggesting a new strategy for making texture surfaces.

3.
BMC Psychiatry ; 24(1): 419, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834943

ABSTRACT

BACKGROUND: Few studies have simultaneously focused on the associations of vegetable and fruit intake, physical activity, school bullying, and Internet addiction (IA) with depressive symptoms. This study aimed to explore the direct and indirect effects of the above factors on depressive symptoms in adolescents by constructing a structural equation model (SEM). METHODS: This study was conducted in Qingdao from September to November 2021. A total of 6195 secondary school students aged 10-19 years were included in the analysis. Information on all variables was assessed using a self-administered questionnaire. An SEM was constructed with depressive symptoms as the endogenous latent variable, IA as the mediating variable, and vegetable and fruit intake, physical activity, and school bullying as the exogenous latent variables. The standardized path coefficients (ß) were the direct effects between the latent variables, and the indirect effects were obtained by the product of direct effects between relevant latent variables. RESULTS: The median value with the interquartile range of depressive symptom scores was 7 (3,12). Vegetable and fruit intake (ß=-0.100, P<0.001) and physical activity (ß=-0.140, P<0.001) were directly negatively related to depressive symptoms. While school bullying (ß=0.138, P<0.001) and IA (ß=0.452, P<0.001) were directly positively related to depressive symptoms. IA had the greatest impact on depressive symptoms. Vegetable and fruit intake, physical activity, and school bullying could not only directly affect depressive symptoms, but also indirectly affect depressive symptoms through the mediating effect of IA, the indirect effects and 95% confidence intervals (CIs) were -0.028 (-0.051, -0.007), -0.114 (-0.148, -0.089) and 0.095 (0.060, 0.157), respectively. The results of the multi-group analysis showed that the SEM we constructed still fit in boy and girl groups. CONCLUSIONS: The results indicated that vegetable and fruit intake, physical activity, school bullying, and IA had a significant direct impact on depressive symptoms, among which IA had the greatest impact. In addition, both vegetable and fruit intake, school bullying, and physical activity indirectly affected depressive symptoms through the mediating effect of IA. The impact of IA on depressive symptoms should be given extra attention by schools and parents. This study provides a scientific and effective basis for the prevention and control of adolescent depressive symptoms.


Subject(s)
Bullying , Depression , Exercise , Fruit , Internet Addiction Disorder , Students , Vegetables , Humans , Adolescent , Male , Bullying/psychology , Bullying/statistics & numerical data , Female , Depression/psychology , Depression/epidemiology , Exercise/psychology , Child , Students/psychology , Students/statistics & numerical data , Internet Addiction Disorder/psychology , Internet Addiction Disorder/epidemiology , Schools , Young Adult , China/epidemiology
4.
Cancer Cell Int ; 24(1): 195, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835070

ABSTRACT

BACKGROUND: Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. METHODS: Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. RESULTS: YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1's inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. CONCLUSIONS: This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.

5.
Cureus ; 16(5): e59607, 2024 May.
Article in English | MEDLINE | ID: mdl-38832183

ABSTRACT

This article presents a case report of a 45-year-old male with neurofibromatosis type I (NF1) who developed a high-grade malignant peripheral nerve sheath tumor (MPNST) originating from a neurofibroma within the common peroneal nerve over popliteal fossa. MPNSTs are aggressive tumors associated with NF1, causing significant mortality. The patient underwent tumor resection surgery and received postoperative radiation therapy. Follow-up examinations showed no impairment of motor function and no tumor recurrence after regular MRI evaluation for four years. This article explores the challenges of distinguishing benign neurofibromas from malignant MPNST via MRI image and biopsy, and achieving a balance between tumor excision and preserving nerve functionality during surgical treatment. However, caution is warranted due to the risk of recurrence.

6.
Metab Eng ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38839038

ABSTRACT

The development of a heme-responsive biosensor for dynamic pathway regulation in eukaryotes has never been reported, posing a challenge for achieving the efficient synthesis of multifunctional hemoproteins and maintaining intracellular heme homeostasis. Herein, a biosensor containing a newly identified heme-responsive promoter, CRISPR/dCas9, and a degradation tag N-degron was designed and optimized to fine-tune heme biosynthesis in the efficient heme-supplying Pichia pastoris P1H9 chassis. After identifying literature-reported promoters insensitive to heme, the endogenous heme-responsive promoters were mined by transcriptomics, and an optimal biosensor was screened from different combinations of regulatory elements. The dynamic regulation pattern of the biosensor was validated by the transcriptional fluctuations of the HEM2 gene involved in heme biosynthesis and the subsequent responsive changes in intracellular heme titers. We demonstrate the efficiency of this regulatory system by improving the production of high-active porcine myoglobin and soy hemoglobin, which can be used to develop artificial meat and artificial metalloenzymes. Moreover, these findings can offer valuable strategies for the synthesis of other hemoproteins.

7.
Article in English | MEDLINE | ID: mdl-38841747

ABSTRACT

Chronic kidney disease is the loss of renal function that can occur from aging or through a myriad of other disease states. Rising serum concentrations of kynurenine, a tryptophan metabolite, have been shown to correlate with increasing severity of chronic kidney disease. This study used chronic intravenous infusion in conscious male Sprague Dawley rats to test the hypothesis that kynurenine can induce renal damage and promote alterations in blood pressure, heart rate and decreased renal function. We found that kynurenine infusion increased mean arterial pressure, increased the maximum and minimum range of heart rate, decreased glomerular filtration rate and induced kidney damage in a dose-dependent manner. This study shows that kynurenine infusion can promote kidney disease in healthy, young rats, implying that the increase in kynurenine levels associated with chronic kidney disease may establish a feed-forward mechanism that exacerbates loss of renal function.

8.
Eur J Oncol Nurs ; 70: 102549, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38692158

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of Orem's self-care model in preparing hospitals for the discharge of patients with colorectal cancer who undergo enterostomy. METHODS: 92 patients with enterostomy were recruited between February 2022 and February 2023 from a general tertiary hospital. The participants were assigned to either the intervention group or the control group randomly. The intervention group received Orem's self-care program and a three-month follow-up, whereas the control group received only routine care and a three-month follow-up. Discharge readiness, self-care ability, and stoma-quality-of-life data were collected at hospital discharge (T1), 30 days (T2), and 90 days (T3) after discharge. RESULTS: The intervention group had substantially higher discharge readiness (knowledge, p < 0.001; coping ability, p = 0.006; personal status, p = 0.001; expected support, p = 0.021; total score, p < 0.001), better self-care ability at T1 (self-care knowledge, p < 0.001; self-care skills, p = 0.010), better total quality of life (QoL) at T1, T2, and T3 (p < 0.001; p = 0.006; p = 0.014); better stoma management and daily routine at T1 (p = 0.004; p < 0.001); and better daily routine at T2 (p = 0.009) than the control group. CONCLUSIONS: The designed discharge readiness program based on Orem's self-care could promote effective patient discharge readiness, self-care knowledge, self-care skills, and QoL. TRIAL REGISTRATION: The trial number ChiCTR2200056302 registered on ClinicalTrials.gov.

9.
Environ Geochem Health ; 46(6): 179, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695935

ABSTRACT

The uncertainty in the generation and formation of non-point source pollution makes it challenging to monitor and control this type of pollution. The SWAT model is frequently used to simulate non-point source pollution in watersheds and is mainly applied to natural watersheds that are less affected by human activities. This study focuses on the Duliujian River Basin (Xiqing section), which is characterized by a dense population and rapid urbanization. Based on the calibrated SWAT model, this study analyzed the effects of land use change on non-point source pollution both temporally and spatially. It was found that nitrogen and phosphorus non-point source pollution load losses were closely related to land use type, with agricultural land and high-density urban land (including rural settlements) being the main contributors to riverine nitrogen and phosphorus pollution. This indicates the necessity of analyzing the impact of land use changes on non-point source pollution loads by identifying critical source areas and altering the land use types that contribute heavily to pollution in these areas. The simulation results of land use type changes in these critical source areas showed that the reduction effect on non-point source pollution load is in the order of forest land > grassland > low-density residential area. To effectively curb surface source pollution in the study area, strategies such as modifying urban land use types, increasing vegetation cover and ground infiltration rate, and strictly controlling the discharge of domestic waste and sewage from urban areas can be implemented.


Subject(s)
Environmental Monitoring , Nitrogen , Phosphorus , Rivers , Water Pollutants, Chemical , Rivers/chemistry , Phosphorus/analysis , Nitrogen/analysis , China , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Urbanization , Non-Point Source Pollution/analysis , Non-Point Source Pollution/prevention & control , Models, Theoretical , Agriculture , Computer Simulation
10.
Aging (Albany NY) ; 16(10): 9251-9263, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38809508

ABSTRACT

BACKGROUND: Senile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an in vitro setting. METHODS: Osteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity in vitro. For mechanistic exploration, RT-PCR and Western blotting were utilized to assess the activation of the NF-κB pathway. Additionally, protein levels of secreted cytokines and growth factors were determined using suspension array technology. RESULTS: Our findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors. CONCLUSIONS: In conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.


Subject(s)
Cell Differentiation , Methylamines , NF-kappa B , Osteoclasts , Oxidative Stress , RANK Ligand , Signal Transduction , Animals , Osteoclasts/drug effects , Osteoclasts/metabolism , Mice , Methylamines/pharmacology , Oxidative Stress/drug effects , Cell Differentiation/drug effects , RAW 264.7 Cells , NF-kappa B/metabolism , RANK Ligand/metabolism , Signal Transduction/drug effects , Macrophage Colony-Stimulating Factor/metabolism , Macrophage Colony-Stimulating Factor/pharmacology , Bone Resorption/metabolism
11.
Am J Trop Med Hyg ; 110(6): 1152-1157, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38697072

ABSTRACT

Soil-transmitted helminthiasis remains a notable health problem in developing countries. In 1990 in Shanghai, a city in eastern China, 47% of the population was affected. Due to a series of comprehensive approaches, the prevalence decreased to 0.5% in 2009. We collected 10-year surveillance data to assess the epidemic situation of soil-transmitted helminth (STH) infections in Shanghai. Stool samples and questionnaires from participants were collected. The Kato-Katz technique was used to detect infections with Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), and Trichuris trichiura. From 2014 to 2023, a total of 77,685 participants were screened for parasitic infections, and the overall prevalence of STH infections decreased from 0.1% to 0% in Shanghai. Of 77,685 participants, 25 (0.03%) were positive for intestinal helminths, with the most common parasite being A. lumbricoides (72.0%). Generally, elderly participants from rural areas with lower education levels were more likely to be infected with STHs. A total of 2,914 questionnaires were collected, and most respondents (72.6%) had good knowledge about the transmission routes of STHs. However, 12.3% of participants did not know the damage to health caused by STHs, and 19.3% had no idea of how to prevent infection. These data demonstrate the current state of STH infections in Shanghai. The results suggest that various comprehensive measures should be encouraged, continuously implemented, and strengthened accordingly so that STH elimination can be integrated into the Healthy China initiative by 2030.


Subject(s)
Ascaris lumbricoides , Helminthiasis , Soil , Humans , China/epidemiology , Helminthiasis/epidemiology , Helminthiasis/transmission , Adult , Soil/parasitology , Middle Aged , Male , Female , Adolescent , Child , Young Adult , Aged , Animals , Prevalence , Ascaris lumbricoides/isolation & purification , Child, Preschool , Feces/parasitology , Ascariasis/epidemiology , Ascariasis/transmission , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/transmission , Trichuriasis/epidemiology , Trichuriasis/transmission , Surveys and Questionnaires , Hookworm Infections/epidemiology , Hookworm Infections/transmission , Infant , Trichuris/isolation & purification
12.
New Phytol ; 243(1): 314-329, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38730532

ABSTRACT

Effector proteins are central to the success of plant pathogens, while immunity in host plants is driven by receptor-mediated recognition of these effectors. Understanding the molecular details of effector-receptor interactions is key for the engineering of novel immune receptors. Here, we experimentally determined the crystal structure of the Puccinia graminis f. sp. tritici (Pgt) effector AvrSr27, which was not accurately predicted using AlphaFold2. We characterised the role of the conserved cysteine residues in AvrSr27 using in vitro biochemical assays and examined Sr27-mediated recognition using transient expression in Nicotiana spp. and wheat protoplasts. The AvrSr27 structure contains a novel ß-strand rich modular fold consisting of two structurally similar domains that bind to Zn2+ ions. The N-terminal domain of AvrSr27 is sufficient for interaction with Sr27 and triggering cell death. We identified two Pgt proteins structurally related to AvrSr27 but with low sequence identity that can also associate with Sr27, albeit more weakly. Though only the full-length proteins, trigger Sr27-dependent cell death in transient expression systems. Collectively, our findings have important implications for utilising protein prediction platforms for effector proteins, and those embarking on bespoke engineering of immunity receptors as solutions to plant disease.


Subject(s)
Fungal Proteins , Nicotiana , Triticum , Zinc , Zinc/metabolism , Triticum/immunology , Triticum/microbiology , Nicotiana/immunology , Nicotiana/microbiology , Nicotiana/metabolism , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Puccinia , Plant Immunity , Protein Binding , Amino Acid Sequence , Cell Death , Protein Domains , Models, Molecular , Plant Diseases/microbiology , Plant Diseases/immunology
13.
Chemosphere ; 359: 142361, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761827

ABSTRACT

The abundance of microplastics (MPs) in soil environments has attracted significant attentions, due to their impact on soil physico-chemical properties. However, limited information is available on the influences of MPs on soil carbon composition and microbial utilization characteristics. Therefore, a two-month incubation experiment was conducted to add polyethylene microplastics (PE-MPs) with different levels (1%, 10%) and sizes (150-300 µm and 75-150 µm) into different soils. After that, soil chemical properties including the dissolved organic carbon (DOC), spectral characteristics of dissolved organic matter (DOM) and soil microbial characteristics were analyzed. Results revealed that PE-MPs addition caused significant differences in soil chemical properties between farmland and woodland soils, particularly in soil pH, DOM composition, and soil phosphatase activity. Woodland soil always exhibited higher levels of DOC content, microbial diversity, and soil carbon source utilization compared to farmland soil, leading to increased humification in the DOM of woodland soil. PE-MPs with a larger particle size significantly increased both the soil DOC content and enzyme activity. Addition of PE-MPs altered the soil DOM composition, and the fluorescence parameters like the biological index (BIX) and humification degree. Moreover, the carbon source utilization intensity of microorganisms on PE MPs-contaminated soils is higher in woodland soils. Various analyses confirmed that compared to other soil properties, characteristics of soil DOM had a more significant impact on soil microbial community composition. Thus, PE-MPs in conjunction with soil DOM spectral characteristics regulated soil microbial diversity, which is crucial for understanding soil carbon sequestration.


Subject(s)
Carbon , Microplastics , Soil Microbiology , Soil Pollutants , Soil , Soil/chemistry , Soil Pollutants/analysis , Carbon/analysis , Microplastics/analysis , Humic Substances/analysis
14.
Biomed Pharmacother ; 175: 116684, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713951

ABSTRACT

Chinese herbs have been used to treat small-cell lung cancer (SCLC) due to their low toxicity and significant efficacy. This study focused on oridonin, a natural compound extracted from Rabdosia rubescens, and aimed to investigate its potential antitumor activity on SCLC and to evaluate the synergistic effect of combining oridonin with other small molecules. In this study, oridonin exhibited a dual effect. At lower concentrations, it suppressed the cell viability of SCLC cells (H1688 and H446). At high concentrations, oridonin induced SCLC cell apoptosis, damaged HBE cells in vitro and compromised the function of the liver and heart in vivo. The lower concentration of oridonin induced autophagy by enhancing the expression of p62 and the LC3B-II/LC3B-I ratio. This phenomenon might be associated with the activation of the protein kinase RNA-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/growth arrest and DNA damage-inducible gene 153 (CHOP/GAD153) pathway. Therefore, the combined effect of oridonin with GSK2606414 or 3- methyladenine increased apoptosis in SCLC cells and reduced tumor growth. A similar phenomenon was observed after oridonin was combined with p62 or CHOP RNA interference treatment. Simultaneously, the combination of oridonin and GSK2606414 exhibited therapeutic efficacy without manifesting adverse effects. Our findings suggest that oridonin at lower concentrations can induce autophagy by activating the PERK/eIF2α/CHOP signaling pathway. The inhibition of the PERK/eIF2α/CHOP pathway could enhance oridonin therapeutic responses by triggering apoptosis. The novel therapeutic approach of combining oridonin with a PERK inhibitor is promising as a strategy for the treatment of SCLC.


Subject(s)
Apoptosis , Autophagy , Diterpenes, Kaurane , Eukaryotic Initiation Factor-2 , Lung Neoplasms , Signal Transduction , Small Cell Lung Carcinoma , Transcription Factor CHOP , eIF-2 Kinase , Diterpenes, Kaurane/pharmacology , Autophagy/drug effects , Transcription Factor CHOP/metabolism , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/metabolism , eIF-2 Kinase/metabolism , Apoptosis/drug effects , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Cell Line, Tumor , Eukaryotic Initiation Factor-2/metabolism , Animals , Signal Transduction/drug effects , Mice, Nude , Mice, Inbred BALB C , Mice , Xenograft Model Antitumor Assays , Cell Survival/drug effects , Drug Synergism , Male
15.
Sci Total Environ ; 938: 173620, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815834

ABSTRACT

Human activity intensity should be controlled within the carrying capacity of soil units, which is crucial for environmental sustainability. However, the existing assessment methods for soil environmental carrying capacity (SECC) rarely consider the relationship between human activity intensity and pollutant emissions, making it difficult to provide effective early warning of human activity intensity. Moreover, there is a lack of spatial high-precision accounting methods for SECC. This study first established a spatial soil environmental capacity (SEC) model based on the pollutant thresholds corresponding to the specific protection target. Next, a spatial net-input flux model was proposed based on soil pollutants' input/output fluxes. Then, the quantitative relationship between human activity intensity and pollutant emissions was established and further incorporated into the SECC model. Finally, the spatial high-precision accounting framework of SECC was proposed. The methodology was used to assess the SECC for the copper production capacity in a typical copper smelting area in China. The results showed that (i) the average SECs for Cu, Cd, Pb, Zn, As and Cr are 427.89, 16.84, 306.41, 376.8, 71.63, and 392.7 kg hm-2, respectively; (ii) heavy metal (HM) concentrations and land-use types jointly influence the spatial distribution pattern of SEC; (iii) atmospheric deposition is the dominant HM input pathway and the high net-input fluxes are mainly located in the southeast of the study area; (iv) with the current human activity intensity for 50 years, the average SECs for Cu, Cd, Pb, Zn, As and Cr are 202.31, 1.71, 20.9, 66.15, 36.73, and 3 kg hm-2, respectively; and (v) to maintain the protection target at the acceptable risk level within 50 years, the SECC for the increased copper production capacity is 1.53 × 106 t. This study provided an effective tool for early warning of human activity intensity.

16.
Int Immunopharmacol ; 136: 112264, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38810308

ABSTRACT

BACKGROUND: Chemotaxis and trafficking of dendritic cells (DCs) induced by cytokine receptors are crucial steps in rheumatoid arthritis (RA) pathogenesis. C-C chemokine receptor type 5 (CCR5) plays a key role in DC movement and has been implicated in multitudinous inflammatory and immunology diseases. Thus, targeting CCR5 to suppress DC chemotaxis is considered as a potential strategy for the management of RA. METHODS: Herein, we first synthesized a new hybrid named CT3-1 which based on artesunate and isatin. Besides, we studied the regulating effectiveness of CT3-1 on bone marrow-derived DCs (BMDCs) and on collagen-induced arthritis (CIA) through RNA-seq analysis, cell function experiments in vitro and mice model in vivo. RESULTS: The results shown that CT3-1 mainly reduced CCR5 expression of immature BMDCs and importantly inhibited immature BMDC migration induced by CCR5 in vitro, with no or minor influence on other functions of DCs, such as phagocytosis and maturation. In the mouse model, CT3-1 relieved arthritis severity and inhibited CIA development. Furthermore, CT3-1 intervention decreased the expression of CCR5 in DCs and reduced the proportion of DCs in the peripheral blood of CIA mice. CONCLUSIONS: Our findings suggest that CCR5-induced chemotaxis and trafficking of immature DCs are important in RA. Targeting CCR5 and inhibiting immature DC chemotaxis may provide a novel choice for the treatment of RA and other similar autoimmune diseases. Moreover, we synthesized a new hybrid compound CT3-1 that could inhibit immature DC trafficking and effectively relieve RA by directly reducing the CCR5 expression of immature DCs.

17.
Rejuvenation Res ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814828

ABSTRACT

INTRODUCTION: To investigate the expression differences of peripheral blood mononuclear cells (PBMCs) in elderly rheumatoid arthritis (ERA) patients. METHOD: Differentially expressed genes (DEGs) of PBMCs between young patients with RA (RA_Y) and aged patients with RA (RA_A) were identified by RNA-seq using the DESeq2 package, followed by bioinformatics analysis. The overlapped targets of the current DEGs and proteomic differentially expressed proteins (another set of unpublished data) were identified and further validated. RESULTS: The bioinformatics analysis revealed significant transcriptomic heterogeneity between RA_A and RA_Y. A total of 348 up-regulated and 363 down-regulated DEGs were identified. Gene functional enrichment analysis indicated that the DEGs, which represented senescence phenotype for ERA patients, were enriched in pathways such as PI3K-Akt signaling, MAPK signaling, toll-like receptor family, neutrophil degranulation, and immune-related pathways. GSEA analysis further confirmed the activation of humoral immune response pathways in RA_A. qPCR validated the expression of five representative DEGs such as, SPTA1, SPTB, VNN1, TNXB and KRT1 in PBMCs of ERA patients. CONCLUSIONS: ERA patients have significantly senescence phenotype differences versus the young patients. The DEGs identified may facilitate exploration the biomarkers of senescence in RA.

18.
PeerJ ; 12: e17314, 2024.
Article in English | MEDLINE | ID: mdl-38799064

ABSTRACT

Background: Despite the Caridean shrimps' vast species richness and ecological diversity, controversies persist in their molecular classification. Within Caridea, the Pandalidae family exemplifies significant taxonomic diversity. As of June 25, 2023, GenBank hosts only nine complete mitochondrial genomes (mitogenomes) for this family. The Plesionika genus within Pandalidae is recognized as polyphyletic. To improve our understanding of the mitogenome evolution and phylogenetic relationships of Caridea, this study introduces three novel mitogenome sequences from the Plesionika genus: P.  ortmanni, P. izumiae and P. lophotes. Methods: The complete mitochondrial genomes of three Plesionika species were sequenced utilizing Illumina's next-generation sequencing (NGS) technology. After assembling and annotating the mitogenomes, we conducted structural analyses to examine circular maps, sequence structure characteristics, base composition, amino acid content, and synonymous codon usage frequency. Additionally, phylogenetic analysis was performed by integrating existing mitogenome sequences of true shrimp available in GenBank. Results: The complete mitogenomes of the three Plesionika species encompass 37 canonical genes, comprising 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (CR). The lengths of these mitogenomes are as follows: 15,908 bp for P. ortmanni, 16,074 bp for P. izumiae and 15,933 bp for P. lophotes. Our analyses extended to their genomic features and structural functions, detailing base composition, gene arrangement, and codon usage. Additionally, we performed selection pressure analysis on the PCGs of all Pandalidae species available in Genbank, indicating evolutionary purification selection acted on the PCGs across Pandalidae species. Compared with the ancestral Caridea, translocation of two tRNA genes, i.e., trnP or trnT, were found in the two newly sequenced Plesionika species-P. izumiae and P. lophotes. We constructed a phylogenetic tree of Caridea using the sequences of 13 PCGs in mitogenomes. The results revealed that family Pandalidae exhibited robust monophyly, while genus Plesionika appeared to be a polyphyletic group. Conclusions: Gene rearrangements within the Pandalidae family were observed for the first time. Furthermore, a significant correlation was discovered between phylogenetics of the Caridea clade and arrangement of mitochondrial genes. Our findings offer a detailed exploration of Plesionika mitogenomes, laying a crucial groundwork for subsequent investigations into genetic diversity, phylogenetic evolution, and selective breeding within this genus.


Subject(s)
Gene Rearrangement , Genome, Mitochondrial , Phylogeny , Animals , Genome, Mitochondrial/genetics , Gene Rearrangement/genetics , Decapoda/genetics , Decapoda/classification , RNA, Transfer/genetics , High-Throughput Nucleotide Sequencing
19.
Endocr J ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38811189

ABSTRACT

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.

20.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1834-1847, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812196

ABSTRACT

This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC) and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS) and network pharmacology. The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model. The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents, while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels. UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb. Multivariate statistical methods were used to screen components increasing significantly after the scorching process. The seven compounds included five free anthraquinones, gallic acid, and 5-hydroxymethylfurfural(HMF). Meanwhile, the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds. Network pharmacology and molecular docking suggested that free anthraquinones, gallic acid, and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2), epidermal growth factor receptor(EGFR), tumor necrosis factor(TNF), and caspase-3(CASP3) and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt), hypoxia inducible factor-1(HIF-1), TNF, and mitogen-activated protein kinase(MAPK), so as to regulate the inflammation response, oxidative stress, and cell apoptosis to relieve UC symptoms. This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb, providing the clinical reference for using rhubarb to treat UC.


Subject(s)
Colitis, Ulcerative , Drugs, Chinese Herbal , Mass Spectrometry , Network Pharmacology , Rheum , Rheum/chemistry , Animals , Colitis, Ulcerative/drug therapy , Mice , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Chromatography, High Pressure Liquid/methods , Male , Humans
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