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1.
Clin Nephrol ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39282890

RESUMO

OBJECTIVE: To construct and apply a risk screening and intervention system for malnutrition in peritoneal dialysis patients based on the Omaha System. MATERIALS AND METHODS: A total of 75 peritoneal dialysis patients were randomly divided into control (38 cases) and intervention group (37 cases). The control group received routine operation training and health education, and the intervention group implemented a nutritional management plan based on the Omaha System. The modified quantitative subjective comprehensive nutritional scale (MQSGA) score, kidney disease dietary compliance attitude (RAAQ) and behavior (RABQ) score, body mass index (BMI), serum albumin (ALB), prealbumin (PA), and hemoglobin (Hb) were observed. RESULTS: Before intervention, there was no significant difference in these indicators between the two groups (p > 0.05). After 6 months, the MQSGA score in the intervention group was significantly lower than that in the control group (p < 0.05). RAAQ score and RABQ score in the intervention group were higher than those in the control group and (p < 0.05), and the nutritional indicators in the intervention group, such as BMI, ALB, PA, and Hb, were higher than those in the control group (p < 0.05). CONCLUSION: A nutritional management plan based on the Omaha System can help improve the nutrition condition of peritoneal dialysis patients, and improve the dietary compliance of chronic kidney disease patients.

2.
Bioact Mater ; 41: 577-596, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39257673

RESUMO

Peripheral nervous system (PNS) injuries often lead to significant sensory and motor impairments. Traditional artificial nerve conduits, lacking anisotropic structures, have been associated with prolonged repair time and failures in nerve regeneration. This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries (PNI). A 3D oriented fibers scaffold featuring distinct radial (RFs) and longitudinal (LFs) fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques. This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures. The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance, effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold. In a rat model with a 10 mm nerve defect, the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks. These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.

3.
Fertil Steril ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39265651

RESUMO

OBJECTIVE: To determine the indications for early rescue intracytoplasmic sperm injection (ICSI) application. DESIGN: A retrospective cohort study SUBJECTS: The study included 19,808 patients who underwent conventional in vitro fertilization (IVF) or rescue ICSI for their first cycles between February 2017 and December 2021. EXPOSURE: Rescue ICSI cycles constituted the study group, where oocytes that had not extruded the second polar body 4-6 hours after insemination were rescued by ICSI. The control group consisted of conventional IVF cycles with no interventions to rescue oocytes without the second polar body. Generalized additive models (GAMs) were constructed to describe the relationship between the second polar body extrusion rate and cumulative live birth rate in conventional IVF and rescue ICSI cycles, respectively. The cutoff value of the second polar body extrusion rate guiding rescue ICSI application was determined from the intersection point of GAMs. Maternal age range applicable to rescue ICSI was further analyzed using the same method. Clinical outcomes were compared between conventional IVF and rescue ICSI cycles across different second polar body extrusion rate and maternal age subgroups. MAIN OUTCOME MEASURES: The second polar body extrusion rate and maternal age range for rescue ICSI application, normal fertilization rate, and cumulative live birth rate. RESULTS: GAMs showed that the cutoff value for the second polar body extrusion rate about rescue ICSI application was 50%. When the rate <50%, normal fertilization rate and cumulative live birth rate (63.7% vs. 46.1%, OR: 1.609, 95% CI: 1.276-2.030) were significantly higher in rescue ICSI cycles than conventional IVF cycles. When the rate ≥50%, rescue ICSI cycles had similar normal fertilization rate and cumulative live birth rate compared to conventional IVF cycles. Further analysis on maternal age in cycles with second polar body extrusion rate <50% released that rescue ICSI cycles showed a higher cumulative live birth rate (67.7% vs. 48.3%, OR: 1.732, 95% CI: 1.361-2.202) than conventional IVF cycles for women aged < 38 years. CONCLUSION: IVF cycles with second polar body extrusion rate <50% in women aged < 38 years was applicable to early rescue ICSI.

4.
Patient Prefer Adherence ; 18: 1907-1918, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296427

RESUMO

Purpose: Our study aimed to explore the current status of patient participation in medication safety from the perspectives of general practitioners (GPs), pharmacists, and outpatients in Beijing, China. Patients and Methods: A qualitative study using semi-structured in-depth individual interviews with GPs, pharmacists, and outpatients. Subjects were identified by purposive sampling until code saturation. Semi-structured qualitative interviews were conducted with GPs, pharmacists, and patients from community health service centers in three urban districts of Beijing, China. The interviews were transcribed verbatim and the text was analysed using thematic analysis techniques including familiarising with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report. Results: A total of eight GPs, seven pharmacists, and 18 outpatients were interviewed. Data analysis led to the generation of five key themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. Patients participated in medication safety in multiple ways. However, insufficient knowledge about medication safety, lack of awareness of the patient's role in ensuring medication safety, shortage of consultation lengths, and being misled by some information were problems with patient participation in medication safety. Conclusion: This exploratory study contributes to our initial understanding of patient participation in medication safety. There were still many issues and barriers in the process of patient participation. Appropriate policies and measures, such as providing various forms of patient education, ensuring sufficient physician-patient communication, giving full play to the role of pharmacists, and making judicious use of digital health tools should be taken to improve medication safety by fully utilising the role of patients.


Medication safety is a significant concern around the world. Patient participation in the medication process is effective in reducing the incidence of medication errors and improving medication safety. However, the role of outpatients with chronic conditions in ensuring medication safety is often neglected. This study aims to explore the perspectives and experiences of GPs, pharmacists, and outpatients by qualitative interviews in Beijing, China. The study involved a series of interviews with eight GPs, seven pharmacists, and 18 outpatients living with noncommunicable diseases. The interview revealed five themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. The findings might help propose suggestions for patient participation in medication safety. Integrating these findings into future studies can help healthcare professionals formulate interventions and better support patients in participating in the medication process.

5.
Environ Pollut ; 361: 124789, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39182810

RESUMO

Enriched microbial communities and their metabolic function were investigated from the three wastewater treatment plants (WWTPs), which were CWWTP (coking wastewater), MWWTP1 (domestic wastewater), and MWWTP2 (mixed wastewater with domestic wastewater and effluent from various industrial WWTPs that contained the mentioned CWWTP). Pollutant types and concentrations differed among the three WWTPs and the reaction units in each WWTP. CWWTP had a higher TCN and phenol concentrations than the MWWTPs, however, in MWWTP2 no phenol was discovered but 0.72 mg/L TCN was found in its anaerobic unit. RDA results revealed that COD, TN, TP, TCN, NO3--N, and phenol were the main factors influencing the microbial communities (P < 0.05). CPCoA confirmed the microbial community difference driven by pollutant types and concentrations (65.1% of variance, P = 0.006). They provided diverse growth environments and ecological niches for microorganisms, shaping unique bacterial community in each WWTP, as: Thiobacillus, Tepidiphilus, Soehngenia, Diaphorobacter in CWWTP; Saccharibacteria, Acidovorax, Flavobacterium, Gp4 in MWWTP1; and Mesorhizobium, Terrimicrobium, Shinella, Oscillochloris in MWWTP2. Group comparative was analyzed and indicated that these unique bacteria exhibited statistically significant difference (P < 0.01) among the WWTPs, and they were the biomarkers in each WWTP respectively. Co-occurrence and coexclusion patterns of bacteria revealed that the most of dominant bacteria in each WWTP were assigned to different modules respectively, and these microorganisms had a closer positive relationship in each module. Consistent with the functional profile prediction, xenobiotics biodegradation and metabolism were higher in CWWTP (3.86%) than other WWTPs. The distinct functional bacteria metabolized particular xenobiotics via oxidoreductases, isomerases, lyases, transferases, decarboxylase, hydroxylase, and hydrolase in each unit or WWTP. These results provided the evidences to support the idea that the pollutant types and concentration put selection stress on microorganisms in the activated sludge, shaping the distinct microbial community structure and function.

6.
Int Immunopharmacol ; 140: 112889, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39128418

RESUMO

This study aimed to characterize PANoptosis-related genes with immunoregulatory features in osteoarthritis (OA) and investigate their potential diagnostic and therapeutic implications. Gene expression data from OA patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis and functional enrichment analysis were conducted to identify PANoptosis-related genes (PRGs) associated with OA pathogenesis. A diagnostic model was developed using LASSO regression, and the diagnostic value of key PRGs was evaluated using Receiver Operating Characteristic Curve (ROC) analysis. The infiltration of immune cells and potential small molecule agents were also examined. A total of 39 differentially expressed PANoptosis-related genes (DE-PRGs) were identified, with functional enrichment analysis revealing their involvement in inflammatory response regulation and immune modulation pathways. Seven key PRGs, including CDKN1A, EZH2, MEG3, NR4A1, PIK3R2, S100A8, and SYVN1, were selected for diagnostic model construction, demonstrating high predictive performance in both training and validation datasets. The correlation between key PRGs and immune cell infiltration was explored. Additionally, molecular docking analysis identified APHA-compound-8 as a potential therapeutic agent targeting key PRGs. This study identified and analyzed PRGs in OA, uncovering their roles in immune regulation. Seven key PRGs were used to construct a diagnostic model with high predictive performance. The identified PRGs' correlation with immune cell infiltration was elucidated, and APHA-compound-8 was highlighted as a potential therapeutic agent. These findings offer novel diagnostic markers and therapeutic targets for OA, warranting further in vivo validation and exploration of clinical applications.


Assuntos
Simulação de Acoplamento Molecular , Osteoartrite , Humanos , Osteoartrite/genética , Osteoartrite/imunologia , Perfilação da Expressão Gênica , Bases de Dados Genéticas , Imunomodulação/genética
7.
BMC Prim Care ; 25(1): 293, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39127640

RESUMO

BACKGROUND: The aim of this study is to explore the influence of GPs'information, motivation and behavior skills on EM prescribing behavior in urban and suburban districts. METHOD: A cross-sectional study was conducted from June to November 2022 cross 3 urban districts and 4 suburban districts in Beijing. The structural equation model was used to analyze the factors influencing the essential medicine prescription behavior among general practitioners in urban and suburban districts. RESULTS: A total of 511 valid questionnaires were collected. There was a statistically significant difference in mean scores for personal motivation and behavioral skills between urban GPs and suburban GPs. For urban GPs, the path analysis revealed that the social motivation had a direct effect on the essential medicine prescribing behavior (ß = 0.225, p < 0.05). In contrast, for suburban GPs, both social motivation and personal motivation had a direct effect on the essential medicine prescribing behavior, respectively (ß = 0.175, p < 0.05; ß = 0.193, p < 0.01). CONCLUSION: Social motivation of urban GPs were positively and significantly associated with essential medicine prescribing behavior. Social motivation and personal motivation of suburban GPs were positively and significantly associated with essential medicine prescribing behavior. Therefore, various corresponding policies and measures should be developed to promote the National Essential Medicines Policy in China.


Assuntos
Clínicos Gerais , Motivação , Padrões de Prática Médica , Humanos , Estudos Transversais , Clínicos Gerais/psicologia , Masculino , Feminino , Padrões de Prática Médica/estatística & dados numéricos , Pequim , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Medicamentos Essenciais/uso terapêutico , Análise de Classes Latentes , China , Atitude do Pessoal de Saúde
8.
Research (Wash D C) ; 7: 0445, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109247

RESUMO

Natural biomaterials have been showing extensive potential in wound healing; attempts therefore focus on productions achieving both antimicrobial and tissue regenerative abilities. Here, we construct a decellularized human colon tumor (DHCT)-derived scaffold for wound remolding via microfluidic bioprinting. The DHCT retains a series of growth factors, fibrin, and the collagen configuration, that favor tissue repair and reconstruction. Specifically, the scaffold shows superior abilities in cell migration and angiogenesis. The biocompatible scaffold is also imparted with tissue adhesion ability and photothermal effect due to the coating of biologically derived polydopamine on the surface. The strong photothermal effect under near-infrared irradiation also present the scaffold with an antibacterial rate exceeding 90%. Furthermore, in vivo experiments convinced that the polydopamine-integrated DHCT scaffold can markedly expedite the healing process of acute extensive wounds. These findings indicate that composite materials derived from natural tumors have substantial potential in pertinent clinical applications.

9.
Int J Mol Med ; 54(4)2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39129277

RESUMO

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT­PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter­EC adhesion proteins (zona occludens­1, connexin 43 and Vascular endothelial­Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl­CoA synthase long­chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter­EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.


Assuntos
Permeabilidade Capilar , Ferroptose , Osteoartrite , Proteína rhoA de Ligação ao GTP , Proteína rhoA de Ligação ao GTP/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Animais , Humanos , Camundongos , Masculino , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Endogâmicos C57BL
10.
J Cell Mol Med ; 28(16): e70027, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39159149

RESUMO

Ageing is the most prominent risk for osteoarthritis (OA) development. This study aimed to investigate the role of phosphoinositide-specific phospholipase Cγ (PLCγ) 1, previously linked to OA progression, in regulating age-related changes in articular cartilage and subchondral bone. d-galactose (d-Gal) was employed to treat chondrocytes from rats and mice or injected intraperitoneally into C57BL/6 mice. RTCA, qPCR, Western blot and immunohistochemistry assays were used to evaluate cell proliferation, matrix synthesis, senescence genes and senescence-associated secretory phenotype, along with PLCγ1 expression. Subchondral bone morphology was assessed through micro-CT. In mice with chondrocyte-specific Plcg1 deficiency (Plcg1flox/flox; Col2a1-CreERT), articular cartilage and subchondral bone were examined over different survival periods. Our results showed that d-Gal induced chondrocyte senescence, expedited articular cartilage ageing and caused subchondral bone abnormalities. In d-Gal-induced chondrocytes, diminished PLCγ1 expression was observed, and its further inhibition by U73122 exacerbated chondrocyte senescence. Plcg1flox/flox; Col2a1-CreERT mice exhibited more pronounced age-related changes in articular cartilage and subchondral bone compared to Plcg1flox/flox mice. Therefore, not only does d-Gal induce senescence in chondrocytes and age-related changes in articular cartilage and subchondral bone, as well as diminished PLCγ1 expression, but PLCγ1 deficiency in chondrocytes may also accelerate age-related changes in articular cartilage and subchondral bone. PLCγ1 may be a promising therapeutic target for mitigating age-related changes in joint tissue.


Assuntos
Cartilagem Articular , Condrócitos , Camundongos Endogâmicos C57BL , Fosfolipase C gama , Animais , Masculino , Camundongos , Ratos , Envelhecimento/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Osso e Ossos/diagnóstico por imagem , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Proliferação de Células , Senescência Celular , Condrócitos/metabolismo , Estrenos/farmacologia , Galactose/metabolismo , Osteoartrite/patologia , Osteoartrite/metabolismo , Osteoartrite/genética , Osteoartrite/etiologia , Fosfolipase C gama/metabolismo , Fosfolipase C gama/genética , Pirrolidinonas/farmacologia
11.
Mol Cell Biol ; : 1-18, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39169784

RESUMO

Osteoarthritis (OA) is a chronic degenerative disease characterized by subchondral osteosclerosis, mainly due to osteoblast activity. This research investigates the function of Sik1, a member of the AMP-activated protein kinase family, in OA. Proteomic analysis was conducted on clinical samples from 30 OA patients, revealing a negative correlation between Sik1 expression and OA. In vitro experiments utilized BMSCs to examine the effect of Sik1 on osteogenic differentiation. BMSCs were cultured and induced toward osteogenesis with specific media. Sik1 overexpression was achieved through lentiviral transfection, followed by analysis of osteogenesis-associated proteins using Western blotting, RT-qPCR, and alkaline phosphate staining. In vivo experiments involved destabilizing the medial meniscus in mice to establish an OA model, assessing the therapeutic potential of Sik1. The CT scans and histological staining were used to analyze subchondral bone alterations and cartilage damage. The findings show that Sik1 downregulation correlates with advanced OA and heightened osteogenic differentiation in BMSCs. Sik1 overexpression inhibits osteogenesis-related markers in vitro and reduces cartilage damage and subchondral osteosclerosis in vivo. Mechanistically, Sik1 modulates osteogenesis and subchondral bone changes through Runx2 activity regulation. The research emphasizes Sik1 as a promising target for treating OA, suggesting its involvement in controlling bone formation and changes in the subchondral osteosclerosis.

12.
J Biol Chem ; 300(9): 107640, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39122006

RESUMO

RBM45 is an RNA-binding protein with roles in neural development by regulating RNA splicing. Its dysfunction and aggregation are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). RBM45 harbors three RRM domains that potentially bind RNA. While the recognitions of RNA by its N-terminal tandem RRM domains (RRM1 and RRM2) have been well understood, the RNA-binding property of its C-terminal RRM (RRM3) remains unclear. In this work, we identified that the RRM3 of the RBM45 sequence specifically binds RNA with a GACG sequence, similar but not identical to those recognized by the RRM1 and RRM2. Further, we determined the crystal structure of RBM45RRM3 in complex with a GACG sequence-containing single-stranded DNA. Our structural results, together with the RNA-binding assays of mutants at key amino acid residues, revealed the molecular mechanism by which RBM45RRM3 recognizes an RNA sequence. Our finding on the RNA-binding property of the individual RRM module of RBM45 provides the foundation for unraveling the RNA-binding characteristics of full-length RBM45 and for understanding the biological functions of RBM45.


Assuntos
Proteínas de Ligação a RNA , RNA , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , RNA/metabolismo , RNA/química , Cristalografia por Raios X , Domínios Proteicos , Ligação Proteica , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Modelos Moleculares , Proteínas do Tecido Nervoso
13.
Polymers (Basel) ; 16(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000660

RESUMO

Negative-tone photosensitive polyimides (PSPIs) with a low coefficient of thermal expansion (CTE) were prepared by dissolving polyimide precursor-poly(amide ester) (PAE) resins, photoinitiators, photocrosslinkers and other additives in organic solvents. Using triamine as a monomer and dianhydride and diamine as polycondensates, tri-branched structure PAE resins with different molecular weights named PAE-1~5 were prepared. A series of corresponding PSPI films named PSPI-1~5 were prepared from PAE-1~5 resins with the same formulation, respectively. The PSPI-1~5 films prepared from resins of this structure have excellent mechanical, thermal and electrical properties after being thermally cured at 350 °C/2 h in nitrogen. The PSPI-1~5 films' coating solution also show good photolithographic performance and are able to obtain photolithographic patterns with a resolution of about 10 µm after homogenization, exposure and development. Among the PSPI-1~5 films, PSPI-2 has the most excellent lithographic properties with a weight average molecular weight (Mw) of 2.9 × 104 g/mol, a CTE of 41 ppk/°C, a glass transition temperature (Tg) of 343 °C and a 5% weight loss temperature (Td5) of 520 °C, making it suitable for industrial scale-up. The mechanical properties of elongation at breakage of 42.4%, tensile moduli of 3.4 GPa and tensile strength of 153.7 MPa were also measured.

14.
Vet Microbiol ; 296: 110189, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39047452

RESUMO

Porcine reproductive and respiratory syndrome (PRRS), which poses substantial threats to the global pig industry, is primarily characterized by interstitial pneumonia. Cluster of differentiation 163 (CD163) is the essential receptor for PRRSV infection. Metalloproteinase-mediated cleavage of CD163 leads to the shedding of soluble CD163 (sCD163), thereby inhibiting PRRSV proliferation. However, the exact cleavage site in CD163 and the potential role of sCD163 in inflammatory responses during PRRSV infection remain unclear. Herein, we found that PRRSV infection increased sCD163 levels, as demonstrated in primary alveolar macrophages (PAMs), immortalized PAM (IPAM) cell lines, and sera from PRRSV-infected piglets. With LC-MS/MS, Arg-1041/Ser-1042 was identified as the cleavage site in porcine CD163, and an IPAM cell line with precise mutation at the cleavage site was constructed. Using the precisely mutated IPAM cells, we found that exogenous addition of sCD163 protein promoted inflammatory responses, while mutation at the CD163 cleavage site suppressed inflammatory responses. Consistently, inhibition of sCD163 using its neutralizing antibodies reduced PRRSV infection-triggered inflammatory responses. Importantly, sCD163 promoted cell polarization from M2 to M1 phenotype, which in turn facilitated inflammatory responses. Taken together, our findings identify sCD163 as a novel proinflammatory mediator and provide valuable insights into the mechanisms underlying the induction of inflammatory responses by PRRSV infection.


Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Inflamação , Macrófagos Alveolares , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Receptores de Superfície Celular , Animais , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígenos de Diferenciação Mielomonocítica/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Suínos , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos CD/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Macrófagos Alveolares/virologia , Macrófagos Alveolares/imunologia , Inflamação/virologia , Linhagem Celular
15.
BMC Med Genomics ; 17(1): 164, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898455

RESUMO

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.


Assuntos
Biologia Computacional , Mieloma Múltiplo , Ubiquitinação , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Biologia Computacional/métodos , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Nomogramas , Análise por Conglomerados
16.
BMC Med ; 22(1): 244, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867192

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.


Assuntos
Craniotomia , Hemorragia Intracraniana Hipertensiva , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hemorragia Intracraniana Hipertensiva/cirurgia , Idoso , Craniotomia/métodos , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Endoscopia/métodos , Adulto
17.
BMC Genomics ; 25(1): 626, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902625

RESUMO

BACKGROUND: Wheat grain endosperm is mainly composed of proteins and starch. The contents and the overall composition of seed storage proteins (SSP) markedly affect the processing quality of wheat flour. Polyploidization results in duplicated chromosomes, and the genomes are often unstable and may result in a large number of gene losses and gene rearrangements. However, the instability of the genome itself, as well as the large number of duplicated genes generated during polyploidy, is an important driving force for genetic innovation. In this study, we compared the differences in starch and SSP, and analyzed the transcriptome and metabolome among Aegilops sharonensis (R7), durum wheat (Z636) and amphidiploid (Z636×R7) to reveal the effects of polyploidization on the synthesis of seed reserve polymers. RESULTS: The total starch and amylose content of Z636×R7 was significantly higher than R7 and lower than Z636. The gliadin and glutenin contents of Z636×R7 were higher than those in Z636 and R7. Through transcriptome analysis, there were 21,037, 2197, 15,090 differentially expressed genes (DEGs) in the three comparison groups of R7 vs Z636, Z636 vs Z636×R7, and Z636×R7 vs R7, respectively, which were mainly enriched in carbon metabolism and amino acid biosynthesis pathways. Transcriptome data and qRT-PCR were combined to analyze the expression levels of genes related to storage polymers. It was found that the expression levels of some starch synthase genes, namely AGP-L, AGP-S and GBSSI in Z636×R7 were higher than in R7 and among the 17 DEGs related to storage proteins, the expression levels of 14 genes in R7 were lower than those in Z636 and Z636×R7. According to the classification analysis of all differential metabolites, most belonged to carboxylic acids and derivatives, and fatty acyls were enriched in the biosynthesis of unsaturated fatty acids, niacin and nicotinamide metabolism, one-carbon pool by folate, etc. CONCLUSION: After allopolyploidization, the expression of genes related to starch synthesis was down-regulated in Z636×R7, and the process of starch synthesis was inhibited, resulting in delayed starch accumulation and prolongation of the seed development process. Therefore, at the same development time point, the starch accumulation of Z636×R7 lagged behind that of Z636. In this study, the expression of the GSe2 gene in Z636×R7 was higher than that of the two parents, which was beneficial to protein synthesis, and increased the protein content. These results eventually led to changes in the synthesis of seed reserve polymers. The current study provided a basis for a greater in-depth understanding of the mechanism of wheat allopolyploid formation and its stable preservation, and also promoted the effective exploitation of high-value alleles.


Assuntos
Aegilops , Sementes , Triticum , Triticum/genética , Triticum/metabolismo , Aegilops/genética , Aegilops/metabolismo , Sementes/genética , Sementes/metabolismo , Hibridização Genética , Poliploidia , Amido/biossíntese , Amido/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteômica/métodos , Multiômica
18.
Diabetes Metab Syndr Obes ; 17: 2283-2291, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859996

RESUMO

Purpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT. Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF<10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases. Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index. Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.

19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(6): 763-768, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38918200

RESUMO

Objective: To review the research progress on the application of three-dimensional (3D) bioprinting technology in auricle repair and reconstruction. Methods: The recent domestic and international research literature on 3D printing and auricle repair and reconstruction was extensively reviewed, and the concept of 3D bioprinting technology and research progress in auricle repair and reconstruction were summarized. Results: The auricle possesses intricate anatomical structure and functionality, necessitating precise tissue reconstruction and morphological replication. Hence, 3D printing technology holds immense potential in auricle reconstruction. In contrast to conventional 3D printing technology, 3D bioprinting technology not only enables the simulation of auricular outer shape but also facilitates the precise distribution of cells within the scaffold during fabrication by incorporating cells into bioink. This approach mimics the composition and structure of natural tissues, thereby favoring the construction of biologically active auricular tissues and enhancing tissue repair outcomes. Conclusion: 3D bioprinting technology enables the reconstruction of auricular tissues, avoiding potential complications associated with traditional autologous cartilage grafting. The primary challenge in current research lies in identifying bioinks that meet both the mechanical requirements of complex tissues and biological criteria.


Assuntos
Bioimpressão , Pavilhão Auricular , Procedimentos de Cirurgia Plástica , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Bioimpressão/métodos , Humanos , Procedimentos de Cirurgia Plástica/métodos , Pavilhão Auricular/cirurgia , Materiais Biocompatíveis
20.
Chemosphere ; 360: 142422, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795916

RESUMO

The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 µg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28-2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO3, PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease.


Assuntos
Nanopartículas Metálicas , Prata , Glândula Tireoide , Poluentes Químicos da Água , Peixe-Zebra , Animais , Prata/toxicidade , Prata/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Poluentes Químicos da Água/toxicidade , Bioacumulação , Tireoglobulina/metabolismo
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