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1.
BMC Biol ; 22(1): 54, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448930

RESUMO

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.


Assuntos
Microbioma Gastrointestinal , Lisina , Animais , Drosophila melanogaster , Disbiose , Bactérias , Imunidade
2.
J Cell Mol Med ; 28(6): e18195, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38429907

RESUMO

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.


Assuntos
Carcinoma , Neoplasias Esofágicas , Metiltransferases , Humanos , Biomarcadores , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Glicólise/genética , Ácido Láctico , Metiltransferases/genética , 60414
3.
Sci Rep ; 14(1): 4042, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369589

RESUMO

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Colorretais , Proteínas com Domínio LIM , Fatores de Transcrição , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Glicólise , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Front Endocrinol (Lausanne) ; 15: 1334609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38390199

RESUMO

Background: Diabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD. Methods: A mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant's perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants' benefits, the data's credibility, and the results' validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy. Discussion: Conducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD. Trial registration number: https://www.chictr.org.cn/, identifier ChiCTR2200062786.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Projetos Piloto , Resultado do Tratamento , Rim , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
BMC Public Health ; 24(1): 499, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365639

RESUMO

BACKGROUND: Chronic kidney disease (CKD), often coexisting with various systemic disorders, may increase the risk of falls. Our study aimed to assess the prevalence and risk of falls among patients with CKD in China. METHODS: We included patients with/without CKD from China Health and Retirement Longitudinal Study (CHARLS). Our primary outcome was the occurrence of fall accidents within the past 2 years. To enhance the robustness of our findings, we employed a multivariable logistic regression model, conducted propensity score analysis, and applied an inverse probability-weighting model. RESULTS: A total of 12,658 participants were included, the prevalence of fall accident rates were 17.1% (2,028/11,837) among participants without CKD and 24.7% (203/821) among those with CKD. In the inverse probability-weighting model, participants with CKD exhibited higher fall accident rates (OR = 1.28, 95% CI: 1.08-1.53, p = 0.005 ). Sensitivity and subgroup analysis showed the results still stable. CONCLUSIONS: The population in China afflicted with CKD has a significantly heightened risk of experiencing falls, underscoring the crucial importance of intensifying efforts in assessing and preventing fall risks.


Assuntos
Insuficiência Renal Crônica , Aposentadoria , Humanos , Estudos Longitudinais , Acidentes por Quedas , Insuficiência Renal Crônica/epidemiologia , China/epidemiologia
6.
Nat Commun ; 15(1): 1116, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321072

RESUMO

Stretchable electronics that prevalently adopt chemically inert metals as sensing layers and interconnect wires have enabled high-fidelity signal acquisition for on-skin applications. However, the weak interfacial interaction between inert metals and elastomers limit the tolerance of the device to external friction interferences. Here, we report an interfacial diffusion-induced cohesion strategy that utilizes hydrophilic polyurethane to wet gold (Au) grains and render them wrapped by strong hydrogen bonding, resulting in a high interfacial binding strength of 1017.6 N/m. By further constructing a nanoscale rough configuration of the polyurethane (RPU), the binding strength of Au-RPU device increases to 1243.4 N/m, which is 100 and 4 times higher than that of conventional polydimethylsiloxane and styrene-ethylene-butylene-styrene-based devices, respectively. The stretchable Au-RPU device can remain good electrical conductivity after 1022 frictions at 130 kPa pressure, and reliably record high-fidelity electrophysiological signals. Furthermore, an anti-friction pressure sensor array is constructed based on Au-RPU interconnect wires, demonstrating a superior mechanical durability for concentrated large pressure acquisition. This chemical modification-free approach of interfacial strengthening for chemically inert metal-based stretchable electronics is promising for three-dimensional integration and on-chip interconnection.

7.
Biofabrication ; 16(2)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38408382

RESUMO

Pressure ulcers (PUs) have emerged as a substantial burden on individuals and society. The introduction of innovative dressings that facilitate the healing of pressure ulcer wounds represents a cost-effective alternative for treatment. In this study, the emphasis is on the preparation of Carthamus tinctorius L. polysaccharide (CTLP) as hydrogel microspheres (MPs), which are then encapsulated within a hydrogel matrix crosslinked with phenylboronic acid gelatin (Gelatin-PBA) andϵ-polylysine-grafted catechol (ϵ-PL-Cat) to enable sustained release for promoting pressure ulcer healing. The presented Gelatin-PBA/ϵ-PL-Cat (GPL)/CTLP-MPs hydrogel demonstrated outstanding self-healing properties. In addition,in vitroexperiments revealed that the hydrogel exhibited remarkable antibacterial activity, excellent biocompatibility. And it showed the capacity to promote vascular formation, effectively scavenge reactive oxygen species, and facilitate macrophage polarization from the M1 to M2 phenotype.In vivowound healing of mice PUs indicated that the prepared GPL/CTLP-MPs hydrogel effectively accelerated the formation of granulation tissue and facilitated the healing of the wounds. In summary,in vivoandin vitroexperiments consistently highlight the therapeutic potential of GPL/CTLP-MPs hydrogel in facilitating the healing process of PUs.


Assuntos
Carthamus tinctorius , Lesão por Pressão , Animais , Camundongos , Hidrogéis/farmacologia , Gelatina , Polilisina/farmacologia , Espécies Reativas de Oxigênio , 60489 , Macrófagos , Antibacterianos/farmacologia , Supuração
8.
Aging (Albany NY) ; 16(4): 3934-3954, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382106

RESUMO

OBJECTIVE: The enzyme Aspartyl tRNA synthetase 2 (DARS2) is a crucial enzyme in the mitochondrial tRNA synthesis pathway, playing a critical role in maintaining normal mitochondrial function and protein synthesis. However, the role of DARS2 in ESCA is unclear. MATERIALS AND METHODS: Transcriptional data of pan-cancer and ESCA were downloaded from UCSC XENA, TCGA, and GEO databases to analyze the differential expression of DARS2 between tumor samples and normal samples, and its correlation with clinicopathological features of ESCA patients. R was used for GO, KEGG, and GSEA functional enrichment analysis of DARS2 co-expression and to analyze the connection of DARS2 with glycolysis and m6A-related genes. In vitro experiments were performed to assess the effects of interfering with DARS2 expression on ESCA cells. TarBase v.8, mirDIP, miRTarBase, ENCORI, and miRNet databases were used to analyze and construct a ceRNA network containing DARS2. RESULTS: DARS2 was overexpressed in various types of tumors. In vitro experiments confirmed that interfering with DARS2 expression significantly affected the proliferation, migration, apoptosis, cell cycle, and glycolysis of ESCA cells. DARS2 may be involved in multiple biological pathways related to tumor development. Furthermore, correlation and differential analysis revealed that DARS2 may regulate ESCA m6A modification through its interaction with METTL3 and YTHDF1. A ceRNA network containing DARS2, DLEU2/has-miR-30a-5p/DARS2, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the upregulation of DARS2 in ESCA and its association with clinical features, glycolysis pathway, m6A modification, and ceRNA network. These discoveries provide valuable insights into the molecular mechanisms underlying ESCA.


Assuntos
Aspartato-tRNA Ligase , Carcinoma , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/genética , Apoptose/genética , Ciclo Celular , Metiltransferases
9.
Onco Targets Ther ; 17: 41-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298550

RESUMO

Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect.

10.
Lung Cancer ; 188: 107449, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184958

RESUMO

BACKGROUND: Sideroflexin 1 (SFXN1) has been discovered as a novel tumor marker for lung adenocarcinoma, but data on its importance in the development of lung adenocarcinoma is still limited. This study evaluated the correlation between SFXN1 and parameters related to 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and further explored the role of SFXN1 in the value-added and glycolytic processes of LUAD. METHOD: The expression and prognostic value of SFXN1 mRNA in LUAD were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data base. Retrospective analysis of 18F-FDG PET imaging and metabolic parameters in 42 patients to explore the relationship between the expression of SFXN1 and glucose metabolism levels in lung adenocarcinoma and its clinical significance. H1975 cells were selected as the in vitro research object, and the biological effects of SFXN1 on LUAD were further elucidated through Edu proliferation assay, CCK8 activity assay, wound healing experiment, and cell flow cytometry. RESULT: SFXN1 is highly expressed in various tumors, including LUAD, and its high expression can serve as an independent predictor of overall survival in lung adenocarcinoma. In addition, the expression of SFXN1 in LUAD was significantly correlated with 18F-FDG PET/CT parameters: maximum and average standardized uptake values (SUVmax and SUVmean), as well as total lesion glycolysis (TLG) (rho = 0.574, 0.589, and 0.338, p < 0.05), which can predict the expression of SFXN1 with an accuracy of 0.934. In vitro functional experiments have shown that knocking down SFXN1 inhibits the proliferation and migration of LUAD cells, promotes cell apoptosis, and may inhibit tumor activity by regulating the expression of glycolytic related genes SLC2A1, HK2, GPI, ALDOA, GAPDH, ENO1, PKM, and LDHA. CONCLUSION: The overexpression of SFXN1 is closely related to FDG uptake, and SFXN1, as a promising prognostic biomarker, may mediate the development of LUAD through the glycolytic pathway.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Fluordesoxiglucose F18/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Biomarcadores
11.
Syst Rev ; 13(1): 23, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217017

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is a common and severe complication of diabetes that can lead to end-stage renal disease with no cure. The first-line drugs recommended by clinical guidelines fail to achieve satisfactory effects for people with DKD. A Chinese herbal medicine Tangshen Qushi Formula (TQF) shows preliminary efficacy and safety in preserving renal function for people with DKD, but the effects on comprehensive renal outcomes remain unclear. We will conduct a systematic review and meta-analysis to evaluate the effects of TQF herbs and their compounds identified from ultra-high performance liquid chromatography-MS/MS in diabetic animal models with renal outcomes. METHODS: This protocol complies with the guideline Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will include studies investigating the effects of TQF herbs and compounds on diabetic rats or mice with renal outcomes. Six electronic databases will be searched from their inception to February 2023. Quality assessment will be conducted using SYRCLE's risk of bias tool. Standardized or weighted mean differences will be estimated for renal outcomes (creatinine, urea, proteinuria, histological changes, oxidative stress, inflammation, and kidney fibrosis). Data will be pooled using random-effects models. Heterogeneity across studies will be expressed as I2. Sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots and Egger's test will be used to explore publication bias. DISCUSSION: The results of this review will provide valuable insights into the potential effects of TQF in managing DKD. The limitation is that the included studies will be animal studies from specific databases, and the interpretation of the findings must be cautious. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023432895. Registered on 19 July 2023 ( https://www.crd.york.ac.uk/PROSPERO/#recordDetails ).


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Plantas Medicinais , Animais , Humanos , Camundongos , Ratos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Rim , Metanálise como Assunto , Revisões Sistemáticas como Assunto/métodos , Espectrometria de Massas em Tandem
12.
Lipids Health Dis ; 23(1): 5, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38185630

RESUMO

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.


Assuntos
Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição Tecidual , Prognóstico , Insuficiência Renal Crônica/terapia , Lipídeos
13.
Aging (Albany NY) ; 16(1): 779-798, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38217547

RESUMO

OBJECTIVE: Spindle pole body component 25 (SPC25) is an important cyclin involved in chromosome segregation and spindle dynamics regulation during mitosis. However, the role of SPC25 in lung adenocarcinoma (LAUD) is unclear. MATERIALS AND METHODS: The differential expression of SPC25 in tumor samples and normal samples was analyzed using TIMER, TCGA, GEO databases, and the correlation between its expression and clinicopathological features and prognosis in LUAD patients. Biological pathways that may be enriched by SPC25 were analyzed using GSEA. In vitro cell experiments were used to evaluate the effect of knocking down SPC25 expression on LUAD cells. Correlation analysis and differential analysis were used to assess the association of SPC25 expression with genes related to cell cycle, glycolysis, and ferroptosis. A ceRNA network involving SPC25 was constructed using multiple database analyses. RESULTS: SPC25 was highly expressed in LUAD, and its expression level could guide staging and predict prognosis. GSEA found that high expression of SPC25 involved multiple cell cycles and glycolytic pathways. Knocking down SPC25 expression significantly affected the proliferation, migration and apoptosis of LUAD cells. Abnormal SPC25 expression levels can affect cell cycle progression, glycolytic ability and ferroptosis regulation. A ceRNA network containing SPC25, SNHG15/hsa-miR-451a/SPC25, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the association of up-regulation of SPC25 in LUAD and its expression with clinical features, prognosis prediction, proliferation migration, cell cycle, glycolysis, ferroptosis, and ceRNA networks. Our results indicate that SPC25 can be used as a biomarker in LUAD therapy and a target for therapeutic intervention.


Assuntos
Adenocarcinoma de Pulmão , Ferroptose , Neoplasias Pulmonares , Humanos , Prognóstico , 60414 , Ferroptose/genética , Corpos Polares do Fuso , Adenocarcinoma de Pulmão/genética , Mitose , Neoplasias Pulmonares/genética , Proteínas Associadas aos Microtúbulos
14.
Int Urol Nephrol ; 56(2): 751-758, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37556106

RESUMO

AIM:  Frailty is common and is reported to be associated with adverse outcomes in patients with chronic diseases in Western countries. However, the prevalence of frailty remains unclear in individuals with chronic kidney disease (CKD) in China. We examined the prevalence of frailty and factors associated with frailty in patients with CKD. METHODS:  This was a cross-sectional analysis of 177 adult patients (mean age 54 ± 15 years, 52% men) with CKD from the open cohort entitled Physical Evaluation and Adverse outcomes for patients with chronic Kidney disease IN Guangdong (PEAKING). Frailty at baseline were assessed by FRAIL scale which included five items: fatigue, resistance, ambulation, illnesses, and loss of weight. Potential risk factors of frailty including age, sex, body mass index, and daily step counts recorded by ActiGraph GT3X + accelerometer were analyzed by multivariate logistic regression analysis. RESULTS: The prevalence of prefrailty and frailty was 50.0% and 11.9% in patients with stages 4-5 CKD, 29.6% and 9.3% in stage 3, and 32.1% and 0 in stages 1-2. In the multivariate logistic regression analysis, an increase of 100 steps per day (OR = 0.95, 95% CI 0.91-0.99, P = 0.01) and an increase of 5 units eGFR (OR = 0.82, 95% CI 0.68-0.99, P = 0.045) were inversely associated with being frail; higher BMI was associated with a higher likelihood of being frail (OR = 1.52, 95% CI 1.11-2.06, P = 0.008) and prefrail (OR = 1.25, 95% CI 1.10-1.42, P = 0.001). CONCLUSION:  Frailty and prefrailty were common in patients with advanced CKD. A lower number of steps per day, lower eGFR, and a higher BMI were associated with frailty in this population.


Assuntos
Fragilidade , Insuficiência Renal Crônica , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fragilidade/epidemiologia , Estudos Transversais , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Idoso Fragilizado
15.
Mol Ther ; 32(2): 313-324, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38093516

RESUMO

Renal fibrosis is a characteristic hallmark of chronic kidney disease (CKD) that ultimately results in renal failure, leaving patients with few therapeutic options. TGF-ß is a master regulator of renal fibrosis and mediates progressive renal fibrosis via both canonical and noncanonical signaling pathways. In the canonical Smad signaling, Smad3 is a key mediator in tissue fibrosis and mediates renal fibrosis via a number of noncoding RNAs (ncRNAs). In this regard, targeting Smad3-dependent ncRNAs may offer a specific therapy for renal fibrosis. This review highlights the significance and innovation of TGF-ß/Smad3-associated ncRNAs as biomarkers and therapeutic targets in renal fibrogenesis. In addition, the underlying mechanisms of these ncRNAs and their future perspectives in the treatment of renal fibrosis are discussed.


Assuntos
Rim , Insuficiência Renal Crônica , Humanos , Fibrose , Rim/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
16.
Front Nutr ; 10: 1279721, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075216

RESUMO

Background and aims: Cognitive impairment (CI) is a prevalent condition in patients with chronic kidney disease (CKD), who face an elevated risk of developing cognitive decline. The fundamental mechanism underlying CI is linked to chronic inflammation, which can be gauged by the Dietary Inflammatory Index (DII). The DII is categorized into anti-inflammatory diets with lower scores and pro-inflammatory diets with higher scores. Specifically, pro-inflammatory diets may contribute to chronic inflammation. However, the correlation between the inflammatory potential of diet and cognitive function in patients with CKD has not been explored. This study aims to investigate the connection between the inflammatory potential of diet and cognitive function in individuals with or without chronic kidney disease. Methods: Data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey (NHANES) were utilized. Participants under the age of 60 or lacking DII, CI, CKD, and other essential data were excluded. DII was computed based on a 24-h dietary recall interview for each participant. Cognitive performance was evaluated using three cognitive tests: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, the Animal Fluency Test (AFT), and the Digital Symbol Substitution Test (DSST). Logistic regression analysis and subgroup analysis were conducted to assess the independent relationship between DII score and CI in the CKD and non-CKD populations. Results: The study included a total of 2069 subjects, with CI prevalence ranging from 21.4 to 23.5%. Multiple regression models showed that after adjusting for all covariates of the three cognitive function tests, higher DII scores were significantly associated with increased risk of CI (CERAD OR = 1.18, 95% CI: 1.1 ~ 1.26, AFT OR = 1.15, 95% CI: 1.08 ~ 1.23, DSST OR = 1.19, 95% CI: 1.11 ~ 1.28). Subgroup analysis indicated that the effect of DII score on CI remained consistent in all subgroups (p > 0.05). Conclusion: Higher DII scores were associated with an increased risk of cognitive impairment in people with or without CKD, suggesting that consuming a pro-inflammatory diet may contribute to the impairment of the cognitive function.

17.
Am J Cancer Res ; 13(9): 3963-3982, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818081

RESUMO

The vesicular nucleotide transporter (SLC17A9) has been overexpressed in various cancers. Nonetheless, little is known about its influence on non-small cell lung cancer (NSCLC), including human lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Integrative bioinformatics analysis was performed to investigate the prognostic significance and underlying mechanisms of SLC17A9 in patients with NSCLC. Here, we found that SLC17A9 up-regulation was significantly correlated with overall survival in LUAD and LUSC (P < 0.05). Gene set enrichment analysis and protein-protein interaction results revealed that SLC17A9 up-regulation was linked to metabolic process, the hallmark of MYC targets, DNA repair, coagulation and complement. SLC17A9 expression was negatively associated with overall survival and positively related to most LUSC immune cells and immunoinhibitor (20/23), particularly immuno A2aR, PD-1, and CTLA-4 (P < 0.001). High SLC17A9 was associated with infiltrating levels of B cells, CD4+ T cells, M1 macrophages, and T cell exhaustion checkpoints such as PD-1, CTLA4, and LAG3 in LUAD. Moreover, Real-time PCR, MTS assay, EdU assay, ATP production assays and cell cycle analysis were performed to validate SLC17A9 knockdown in LUAD cells. SLC17A9 knockdown significantly inhibited cell proliferation and ATP levels by affecting P2X1, Cytochrome C, and STAT3 expression in lung cancer cells. In conclusion, the present study suggested that SLC17A9 could potentially serve as a prognostic biomarker and correlated with immune infiltrates in LUAD and LUSC.

18.
BMC Nephrol ; 24(1): 262, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667217

RESUMO

BACKGROUND: The 2017 Oxford classification of immunoglobulin A nephropathy (IgAN) recently reported that crescents could predict a worse renal outcome. Early prediction of crescent formation can help physicians determine the appropriate intervention, and thus, improve the outcomes. Therefore, we aimed to establish a nomogram model for the prediction of crescent formation in IgA nephropathy patients. METHODS: We retrospectively analyzed 200 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator(LASSO) regression and multivariate logistic regression was applied to screen for influencing factors of crescent formation in IgAN patients. The performance of the proposed nomogram was evaluated based on Harrell's concordance index (C-index), calibration plot, and decision curve analysis. RESULTS: Multivariate logistic analysis showed that urinary protein ≥ 1 g (OR = 3.129, 95%CI = 1.454-6.732), urinary red blood cell (URBC) counts ≥ 30/ul (OR = 3.190, 95%CI = 1.590-6.402), mALBU ≥ 1500 mg/L(OR = 2.330, 95%CI = 1.008-5.386), eGFR < 60ml/min/1.73m2(OR = 2.295, 95%CI = 1.016-5.187), Serum IgA/C3 ratio ≥ 2.59 (OR = 2.505, 95%CI = 1.241-5.057), were independent risk factors for crescent formation. Incorporating these factors, our model achieved well-fitted calibration curves and a good C-index of 0.776 (95%CI [0.711-0.840]) in predicting crescent formation. CONCLUSIONS: Our nomogram showed good calibration and was effective in predicting crescent formation risk in IgAN patients.


Assuntos
Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/diagnóstico , Estudos Retrospectivos , Nomogramas , Rim , Calibragem
19.
J Transl Med ; 21(1): 574, 2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37626419

RESUMO

BACKGROUND: This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. METHODS: This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. RESULTS: DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. CONCLUSIONS: Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Aspartato-tRNA Ligase , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Glicólise , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética
20.
Adv Rheumatol ; 63(1): 32, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464372

RESUMO

BACKGROUND: Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate crystals in joints, cartilage, and kidneys. Although Tongfengding capsules, a Chinese patent medicine, have long been used to treat gout, their effects and safety have not been reviewed systematically. This study evaluated its efficacy and safety for gout in adults. METHODS: Randomized controlled trials involving Tongfengding capsule for gout in adults were searched from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CBM, CNKI, and VIP databases, and analyzed using the Cochrane Handbook criteria. The primary outcome measures were the total effective rate. The secondary outcome measures including the blood uric acid (BUA), 24-h urinary total protein (24-h UTP), blood urea nitrogen (BUN), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and adverse effects. The risk of bias was evaluated in all included studies. RevMan ver. 5.3.5 and GRADE profiler was used for data analysis and assessing the quality of evidence, respectively. RESULTS: Six studies (n = 607 Chinese participants) were included. Tongfengding capsules plus conventional treatment significantly increased the total effective rate (RR 1.21, 95% CI 1.11-1.33), while reducing the BUA (MD - 66.05 µmol/L, 95% CI - 81.26 to - 50.84), 24-h UTP (MD - 0.83 g/24 h, 95% CI - 0.96 to - 0.70), BUN (MD - 0.90 mmol/L, 95% CI - 1.60 to - 0.20), IL-6 (MD - 6.99 ng/L, 95% CI - 13.22 to - 0.75), IL-8 (MD - 12.17 ng/L, 95% CI - 18.07 to - 6.27), TNF-α (MD - 8.50 ng/L, 95% CI - 15.50 to - 1.51), and adverse effects (RR 0.21, 95% CI 0.04-0.95). CONCLUSION: Tongfengding capsules plus conventional treatment is safe and beneficial for adults with gout compared with conventional treatment.


Assuntos
Gota , Ácido Úrico , Adulto , Humanos , Medicamentos sem Prescrição , Fator de Necrose Tumoral alfa , Cápsulas , Interleucina-8 , Uridina Trifosfato , Gota/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
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