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1.
Front Nutr ; 11: 1358017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903629

RESUMO

Purpose: With the prevalence of high body mass index (HBMI) increasing over the past 30 years, it is essential to examine the impact of obesity on kidney cancer. This study aims to explore the attributable burden of kidney cancer associated with HBMI and its proportion at different levels. Methods and materials: The data used in this research were obtained from the Global Burden of Diseases Study 2019. We utilized DisMod-MR 2.1, a Bayesian meta-regression tool, to estimate the burden of kidney cancer attributable to HBMI, which was measured by age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR). Correlation analysis was conducted by the Spearman rank order correlation method. The temporal trends were analyzed by estimating the estimated annual percentage change (EAPC). Results: Globally in 2019, there were a total of 31.7 thousand deaths and 751.89 thousand disability-adjusted life years (DALYs) attributable to kidney cancer caused by HBMI, increased by 183.1 and 164%, respectively. Over the period from 1990 to 2019, the burden of kidney cancer attributable to HBMI increased in all regions, with the most significant increases occurring in Low-middle socio-demographic index (SDI) and Low SDI regions. At the national level, countries with lower SDI had lower ASMR and ASDR compared to developed nations. However, the EAPC values, which indicate the rate of increase, were significantly higher in these countries than in developed nations. Furthermore, across all years from 1990 to 2019, males experienced a greater and more rapidly increasing burden of kidney cancer attributable to HBMI than females. Conclusion: As the population grows and dietary patterns shift, the burden of kidney cancer attributable to HBMI is expected to become even more severe. Males and developed regions have borne a heavier burden from 1990 to 2019. However, the EAPC values for both ASMR and ASDR were higher in males but not in regions with higher SDI values.

2.
Carbohydr Polym ; 339: 122250, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823917

RESUMO

Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.


Assuntos
Acne Vulgar , Glycyrrhiza , Nanopartículas , Polissacarídeos , Dióxido de Silício , Glycyrrhiza/química , Dióxido de Silício/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Nanopartículas/química , Animais , Porosidade , Acne Vulgar/tratamento farmacológico , Camundongos , Administração Tópica , Humanos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Indóis , Polímeros
3.
Front Psychiatry ; 15: 1376867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807691

RESUMO

Objectives: Online mindfulness-based program (MBP) for parents and families especially in clinical population is limited. Engagement and significant dropout are major issues in MBP implementation. This pilot study examined the effects of an online mindfulness-based program (MBP) on parents of children with Attention Deficit/Hyperactivity Disorder (ADHD). Methods: A mixed methods study was applied to evaluate the effects of the MBP. A total of 43 parents were recruited and were randomly assigned into intervention group and waitlist control group. The online MBP lasted for 28 days, including 20 psychoeducation videos, homework audio guidance, and four instructor-led online group meetings. Purposive sampling was used to recruit parents who completed the program to share their experiences and suggestions for improving the program in semi-structured online interviews. Results: Quantitative data showed that participants from the online MBP reported a medium to large effect on the reduction of child ADHD symptoms. In semi-structured interviews, participants reported positive experiences in their help seeking intention, and personal changes, such as emotion regulation and quality attention to their children. Participants further made suggestions for improvement. Conclusions: The effect of online MBP is promising, and the program should be conducted. A large scale randomized controlled trial should be conducted to investigate the effects of MBP in clinical populations. Clinical trial registration: ClinicalTrials.gov NCT05480423.

4.
J Integr Neurosci ; 23(5): 89, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38812380

RESUMO

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.


Assuntos
Sensibilização do Sistema Nervoso Central , Neuralgia , Neuralgia/terapia , Neuralgia/fisiopatologia , Humanos , Sensibilização do Sistema Nervoso Central/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo
5.
Heliyon ; 10(10): e31192, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813236

RESUMO

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

6.
Int J Biol Macromol ; 267(Pt 2): 131551, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621566

RESUMO

Gentiana dahurica Fisch. (G. dahurica) is one of the legitimate sources of Qinjiao in Traditional Chinese Medicine (TCM) and grows on high-altitude plateaus. Plants develop unique biochemical accumulations to resist plateau conditions, especially the strong UV irradiation. Thus, this study aimed to investigate the polysaccharide of G. dahurica (GDP), its structure and its activity against UVB irradiation. Four GDPs were isolated and two of them were subjected to structural elucidation. The results suggested that GDP-1 has 53.5 % Ara and 30.8 % GalA as its main monosaccharides, with a molecular weight (Mw) of 23 kDa; the GDP-2 has 33.9 % Ara and 48.5 % GalA, with a Mw of 82 kDa. Methylation and NMR spectroscopy analysis revealed that GDP-1 contains →5)-α-Araf-(1 â†’ 5)-α-Araf-(1 â†’ 3,5)-α-Araf-(1 â†’ 3,4)-α-GalpA-(6-OMe)-(1→ as the main chain, the branches of GalA (with esterification), and the terminal Ara; the GDP-2 contains →4)-α-GalpA-(1 â†’ 4)-α-GalpA-(6-OMe)-(1 â†’ 5)-α-Araf-(1 â†’ 3,5)-α-Araf-(1→ as the main chain, the branches of →5)-α-Araf-(1-5)-α-Araf, and the terminal GalA. Both GDP-1 and GDP-2 exhibited concentration-dependent antioxidant activity against DPPH, ABTS and hydroxyl radicals. Moreover, GDPs significantly attenuated the decreases in viability and proliferation of HaCaT cells after UVB irradiation. They can scavenge reactive oxygen species (ROS) and improve the activities of endogenous antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH). The potential mechanism explored by flow cytometry assays of cell apoptosis and cell cycle distribution suggested that GDPs exert protective effects against UVB irradiation by reducing ROS and attenuating S phase cell arrest. In brief, the GDP-1 and GDP-2 are α-1,3- and α-1,4- arabinogalacturonan, respectively. The high content of Ara could be attributed to biochemical accumulation in resisting to the plateau environment and to prevent UVB irradiation-related damage in cells. These findings provide insight into authentic medicinal herbs and the development of GDPs in the modern pharmaceutical and cosmetics industry.


Assuntos
Antioxidantes , Gentiana , Polissacarídeos , Raios Ultravioleta , Polissacarídeos/farmacologia , Polissacarídeos/química , Gentiana/química , Antioxidantes/farmacologia , Antioxidantes/química , Humanos , Monossacarídeos/análise , Peso Molecular , Metilação , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Protetores contra Radiação/isolamento & purificação
7.
Med Sci Monit ; 30: e942888, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576138

RESUMO

BACKGROUND This retrospective study aimed to compare patient outcomes from standard total knee arthroplasty (TKA) vs navigation-guided arthroplasty using the Brainlab software-guided surgical system at Cangzhou Hospital of Integrated TCM-WM, Hebei, Hebei Province, China from January 2021 to July 2023. MATERIAL AND METHODS A total of 239 patients who underwent total knee arthroplasty in Cangzhou Hospital of Integrated TCM-WM, Hebei from January 2021 to July 2023 were retrospectively analyzed. According to the inclusion criteria, 212 eligible patients were selected for analysis and divided into a Navigation Group (NG) (n=105) and a Traditional Group (TG) (n=107) according to surgical method used. Outcomes measured included duration of disease, operative time, intraoperative blood loss volume, postoperative length of hospital stay, and pain measured by the hospital for special surgery knee score (HSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and forgotten joint score (FJS). RESULTS The comparison of perioperative results between the 2 groups showed that the incision length in the NG was significantly longer than that in the TG (P<0.001, 95% Cl 2.59-3.35). At 3 months after surgery, the HSS score of the NG was statistically higher than that of the TG (P=0.002, 95% Cl 3.42-4.46); the WOMAC score of the NG was lower than that of the TG (P<0.001, 95% Cl -4.41-2.87); and the FJS score of the NG was significantly higher than that of the TG (P=0.003, 95% Cl 2.39-3.67). CONCLUSIONS Compared with conventional TKA, use of the Brainlab navigation system is associated with a longer incision, more accurate implantation position of the prosthesis, faster recovery of knee joint function, and helps patients to "forget" about their knee prosthesis in the short term.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Ferida Cirúrgica , Humanos , Artroplastia do Joelho/métodos , Estudos Retrospectivos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Resultado do Tratamento
8.
Biol Reprod ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582608

RESUMO

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.

9.
Int J Biol Macromol ; 266(Pt 1): 130725, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490394

RESUMO

Carrageenan (CGN) is a typical sulfated polysaccharide widely applied in the food and pharmaceutical industries. Its in vivo behavior plays vital roles in understanding structural and biological functional relationships. The lack of UV chromophores in highly sulfated polysaccharides presents a challenge for their in vivo behavior studies. Therefore, this study aimed to develop a fast and effective quantitative fluorescence method for investigating the pharmacokinetics and tissue distribution of CGN. Fluorescence isothiocyanate labeling of CGN (FCGN) and microplate reader-based measurements were developed and validated to study its pharmacokinetics. These results showed that the FCGN concentration peaked at 3 h, the mean residence time was 36.6 h, and the clearance rate was 0.1 L/h/kg. Most of the FCGN was excreted in the feces, while 9.2 % was excreted in the urine, suggesting absorption and metabolism. The pharmacokinetic parameters indicated that the FCGN was absorbed quickly, eliminated slowly, and could remain in the body for a sustained profile. Moreover, ex vivo imaging and quantification of FCGN in tissues revealed that FCGN accumulated in the liver and kidney. Furthermore, oral administration of CGN or KOs for 14 days led to changes in liver and kidney indices. Histological analysis of significant organs revealed hepatocyte necrosis in the liver, renal tubular vacuolization in the kidney, and incomplete colonic epithelial cells. The KOs had a more significant effect on inflammatory cell infiltration than did CGNs. These in vivo findings laid the foundation for the study and application of CGN in food and pharmaceutical applications.


Assuntos
Carragenina , Animais , Camundongos , Distribuição Tecidual , Administração Oral , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo
10.
Liver Int ; 44(6): 1351-1362, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38436551

RESUMO

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Invasividade Neoplásica , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Microvasos/diagnóstico por imagem , Microvasos/patologia , Intervalo Livre de Doença , Recidiva Local de Neoplasia
11.
World J Clin Oncol ; 15(2): 302-316, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38455139

RESUMO

BACKGROUND: Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. AIM: To investigate the biological function and mechanism of TM9SF1 in BC. METHODS: Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. RESULTS: Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. CONCLUSION: TM9SF1 may be an oncogene in BC.

12.
Front Nutr ; 11: 1218912, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481974

RESUMO

Objectives: The associations of posteriori dietary patterns with the risk of hyperuricemia (HUA) are contradictory. Several fair-quality observational studies with inconsistent results have been published following a prior review. Herein, we carried out an updated systematic review and meta-analysis to quantitatively analyze the aforementioned relationships. Methods: Our analysis protocol has been registered with PROSPEPO (Number: CRD42022376745). English publications were searched in Embase, PubMed, and Web of Science from inception to January 1, 2024. Summary odds ratio (OR) and 95% confidence intervals (CIs) were calculated by a random-effects model. We also conducted subgroup, sensitivity, and meta-regression analyses and publication bias assessments. Results: Thirteen studies with a total of 163,192 participants were included in the current meta-analysis. Our finding revealed that the plant-based pattern was linked with a 17% decreased risk of HUA (OR = 0.83, 95%CI = 0.72-0.94, I2 = 72.9%, n = 10). There was no evidence of publication bias in the present analysis. The results of subgroup analyses were generally consistent with the main findings. In meta-regression analyses, no evidence of heterogeneity was detected in the subgroups. Furthermore, our analyses indicated that the animal-based food pattern (OR = 1.36, 95%CI = 1.25-1.47, I2 = 26.7%, n = 11) and sweet food pattern (OR = 1.24, 95%CI = 1.06-1.46, I2 = 0, n = 2) was related to an increased risk of HUA. Conclusion: The plant-based pattern is inversely correlated with HUA risk, whereas animal-based food patterns and sweet food patterns are positively correlated with HUA risk.

13.
Mol Biotechnol ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514598

RESUMO

Genomic epigenetics of extracellular matrix (ECM) play an important role in lung adenocarcinoma (LUAD). Our study identified a signature of potential prognostic genes associated with ECM and constructed immune risk-related prognosis model in LUAD. We downloaded mRNAs transcriptome data, miRNAs expression data, and clinical patient information for LUAD based on The Cancer Genome Atlas. "Limma, clusterProfiler, ggplot2" R packages and GSEA were used to analyze meaningful genes and explore potential biological function. A competing endogenous RNA network was constructed to reveal the mechanism of ECM-related genes. Combined with clinical LUAD patients' characteristics, univariate and multivariate Cox regression analyses were used to build prognostic immune risk model. Next, we calculated AUC value of ROC curve, and explored survival probability of different risk groups. A total of 2966 mRNAs were differently expressed in LUAD samples and normal samples. Function enrichment analyses proved mRNAs were associated with many tumor pathways, such as cell adhesion, vascular smooth muscle contraction, and cell cycle. There were 18 mRNAs related to ECM receptor signaling pathway, and 7 mRNAs expressions were correlated with EGFR expression, but only 5mRNAs were associated with the long-term prognosis. Based on Integrin alpha-8 (ITGA8) molecule, we identified potential 3 miRNAs from several databases. The promoter of ITGA8 was higher-methylated and lower-expressed in LUAD. And lower-expressed group has poor prognosis for patients. 66 immunomodulators related to ITGA8 were performed to construct immune correlation prediction model (p < 0.05). Comprehensive analyses of ITGA8 revealed it combined focal adhesion kinase to activate PI3K/AKT signaling pathway to influence the occurrence and development of LUAD. A novel immune prognostic model about ITGA8 was constructed and verified in LUAD patients. Combined with non-coding genes and genomic epigenetics, identification of potential biomarkers provided new light on therapeutic strategy for clinical patients.

14.
Anticancer Drugs ; 35(6): 584-596, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38518088

RESUMO

Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.


Assuntos
Neoplasias da Mama , Inibidores de Proteínas Quinases , Receptor ErbB-2 , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Feminino , Inibidores de Proteínas Quinases/uso terapêutico , Lapatinib/uso terapêutico , Antineoplásicos/uso terapêutico , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Acrilamidas , Aminoquinolinas
15.
Environ Sci Pollut Res Int ; 31(13): 19779-19794, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38366319

RESUMO

Comprehending the spatial-temporal characteristics, contributions, and evolution of driving factors in agricultural non-CO2 greenhouse gas (GHG) emissions at a macro level is pivotal in pursuing temperature control objectives and achieving China's strategic goals related to carbon peak and carbon neutrality. This study employs the Intergovernmental Panel on Climate Change (IPCC) carbon emissions coefficient method to comprehensively evaluate agricultural non-CO2 GHG emissions at the provincial level. Subsequently, the contributions and spatial-temporal evolution of six driving factors derived from the Kaya identity were quantitatively explored using the Logarithmic Mean Divisia Index (LMDI) and Geographical and Temporal Weighted Regression (GTWR) methods. The results revealed that the distribution of agricultural non-CO2 GHG emissions is shifting from the central provinces to the northwest regions. Moreover, the dominant driving factors of agricultural non-CO2 GHG emissions were primarily economic factor (EDL) with positive impact (cumulative promotion is 2939.61 million metric tons (Mt)), alongside agricultural production efficiency factor (EI) with negative impact (cumulative reduction is 2208.98 Mt). Influence of EDL diminished in the eastern coastal regions but significantly impacted underdeveloped regions such as the northwest and southwest. In the eastern coastal regions, EI gradually became the absolute dominant driver, demonstrating a rapid reduction effect. Additionally, a declining birth rate and rural-to-urban population migration have significantly amplified the driving effects of the population factor (RP) at a national scale. These findings, in conjunction with the disparities in geographic and socioeconomic development among provinces, can serve as a guiding framework for the development of a region-specific roadmap aimed at reducing agricultural non-CO2 GHG emissions.


Assuntos
Gases de Efeito Estufa , Agricultura , Dióxido de Carbono/análise , China , Carbono , Efeito Estufa
16.
Am J Chin Med ; 52(1): 253-274, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38351702

RESUMO

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.


Assuntos
Berberina , Diabetes Mellitus Tipo 2 , Doenças Mitocondriais , Camundongos , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Glucose , Obesidade/metabolismo , Estresse Oxidativo , Doenças Mitocondriais/tratamento farmacológico
17.
Int J Biol Macromol ; 261(Pt 2): 129709, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286380

RESUMO

The dried root of Pueraria mirifica (P. mirifica) is an edible foodstuff widely used in Asian countries. P. mirifica is known for its high starch content. The isolation of polysaccharides from high-starch plant parts is challenging due to the interference of starch. Therefore, this study aimed to develop a technique for isolating and investigating the structure and activity of non-glucan polysaccharides from P. mirifica (PMP). An effective starch removal process was developed using α-amylase hydrolysis and thorough membrane dialysis. Four non-glucan polysaccharides were isolated, and PMP-2 was subjected to structural elucidation. The results indicated that PMP-2 has a molecular weight of 124.4 kDa and that arabinose and galactose are the main components, accounting for 27.8 % and 58.5 %, respectively. Methylation and NMR analysis suggested that PMP-2 is an Arabinogalactan composed of 1,6-linked Galp and 1,4-linked Galp as the main chain, with arabinan and rhamnose as side chains. Furthermore, PMP-C and PMP-2 exhibited concentration-dependent antioxidant activities against DPPH, ABTS, and hydroxyl radicals and certain immunomodulatory activities related to the release of NO, TNF-α and IL-6. These findings suggest that PMP-2 has potential therapeutically active ingredient in functional foods. The developed method successfully removed starch and isolated non-glucan polysaccharides from the high-starch content plant P. mirifica and can be applied to other high-starch plants.


Assuntos
Pueraria , Pueraria/química , Amido , Diálise Renal , Extratos Vegetais , Antioxidantes , Polissacarídeos/farmacologia
18.
IEEE Trans Med Imaging ; 43(2): 820-831, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37801381

RESUMO

Image segmentation is essential to medical image analysis as it provides the labeled regions of interest for the subsequent diagnosis and treatment. However, fully-supervised segmentation methods require high-quality annotations produced by experts, which is laborious and expensive. In addition, when performing segmentation on another unlabeled image modality, the segmentation performance will be adversely affected due to the domain shift. Unsupervised domain adaptation (UDA) is an effective way to tackle these problems, but the performance of the existing methods is still desired to improve. Also, despite the effectiveness of recent Transformer-based methods in medical image segmentation, the adaptability of Transformers is rarely investigated. In this paper, we present a novel UDA framework using a Transformer for building a cross-modality segmentation method with the advantages of learning long-range dependencies and transferring attentive information. To fully utilize the attention learned by the Transformer in UDA, we propose Meta Attention (MA) and use it to perform a fully attention-based alignment scheme, which can learn the hierarchical consistencies of attention and transfer more discriminative information between two modalities. We have conducted extensive experiments on cross-modality segmentation using three datasets, including a whole heart segmentation dataset (MMWHS), an abdominal organ segmentation dataset, and a brain tumor segmentation dataset. The promising results show that our method can significantly improve performance compared with the state-of-the-art UDA methods.


Assuntos
Neoplasias Encefálicas , Humanos , Processamento de Imagem Assistida por Computador
19.
Endocrine ; 83(2): 488-493, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37749390

RESUMO

PURPOSE: Kallmann syndrome is a rare disease characterized by delayed puberty, infertility and anosmia. We report the clinical and genetic characteristics of three patients with Kallmann syndrome who presented with Klinefelter syndrome and defined this neglected combined form of hypogonadism as mixed hypogonadism. METHODS: Clinical data and examinations were obtained, including laboratory examination and magnetic resonance imagination (MRI) of the olfactory structures. Congenital hypogonadotropic hypogonadism (CHH) related genes were screened by next generation sequencing (NGS). RESULTS: Three patients with Kallmann syndrome were included. They had co-existence with Klinefelter syndrome and showed hypogonadotropic hypogonadism. Patient 1 was complicated with germinoma. CONCLUSION: Mixed hypogonadism was defined as hypogonadotropic hypogonadism in Klinefelter syndrome or primary testicular disease. Clinicians should be alert to mixed hypogonadism when spermatogenesis induction failed in patients with CHH or gonadotropin levels decrease in patients with Klinefelter syndrome.


Assuntos
Hipogonadismo , Infertilidade , Síndrome de Kallmann , Síndrome de Klinefelter , Masculino , Humanos , Síndrome de Kallmann/complicações , Síndrome de Klinefelter/complicações , Hipogonadismo/etiologia , Testículo
20.
Orthop Surg ; 16(2): 514-520, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38111022

RESUMO

BACKGROUND: With the development of spinal endoscopic techniques, on the basis of our previous experience in treating various types of cervical disc herniation with this endoscopic technique, we took the lead in applying the percutaneous fully endoscopic anterior transcorporeal procedure to be utilized in the treatment of the isolated cervical ossification of the posterior longitudinal ligament (OPLL). CASE PRESENTATION: A 66-year-old male patient who weighed 57 kg, with a height of 169 cm was admitted to the hospital on September 16, 2021 because of recurrent pain and numbness in the neck, shoulder, and right arm for 2 years, which as aggravated for the last 2 weeks. Two years ago, the patient developed neck and shoulder pain accompanied by right arm pain without obvious predisposing factors, and numbness in the first web space of the right hand. In the last 2 weeks, he had difficulty moving the right arm, but no pain or numbness in the contralateral arm. MRI and CT scans demonstrated that the ossified posterior longitudinal ligament of the cervical 5/6 vertebrae with spinal canal stenosis and seriously compressed the spinal cord patient was treated with a percutaneous fully endoscopic anterior transcorporeal procedure. CONCLUSION: Our percutaneous fully endoscopic anterior transcorporeal procedure is a feasible, minimally invasive surgery for treating isolated ossification of the posterior longitudinal ligament in the cervical spine.


Assuntos
Ligamentos Longitudinais , Ossificação do Ligamento Longitudinal Posterior , Masculino , Humanos , Idoso , Hipestesia/complicações , Osteogênese , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Dor , Resultado do Tratamento
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