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1.
Nutr Cancer ; : 1-9, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775076

RESUMO

Vitamin B12 plays a role in DNA methylation, influencing the 1-carbon cycle; However, its effect on colorectal cancer (CRC) mortality remains uncertain. This study assessed the relationship between vitamin B12 intake and all-cause and cancer-specific mortality among CRC patients. We analyzed data from the NHANES from 1999 to 2018, using multivariable Cox regression, competing risk model, Kaplan-Meier survival curves, and stratified analysis with interaction effects. The studied involved 4,554 cancer patients (mean age 65.8 years, 47.6% males). Results from multivariate Cox regression indicated that each additional 1 mcg/day of dietary vitamin B12 independently increased the risk of all-cause (HR, 1.07; 95% CI: 1.04-1.09, p < 0.001) and cancer-specific mortality (HR, 1.04; 95% CI, 1.02-1.06; p < 0.001). Kaplan-Meier curves indicated a higher risk of all-cause mortality with increased vitamin B12 intake (Log rank p = 0.01). Subgroup analysis suggested that higher vitamin B12 intake correlated with increased all-cause mortality risk, especially in individuals with higher protein (HR, 1.04; 95% CI, 1.02-1.06; p = 0.019) or carbohydrate intake (HR, 1.03; 95% CI, 1.01-1.05; p = 0.04). Thus, higher vitamin B12 intake correlates with increased all-cause and cancer-specific mortality in CRC patients, particularly those with higher protein or carbohydrate intake.

2.
Front Public Health ; 12: 1370765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737857

RESUMO

Background: Occupational health is closely related to harmful factors in the workplace. Dust is the primary contributing factor causing impaired lung ventilation function among employees with dust exposure, and their lung ventilation function may also be influenced by other factors. We aimed at assessing the status and influencing factors of lung ventilation function among employees exposed to dust in the enterprises of the Eighth Division located in the Xinjiang Production and Construction Corps (XPCC), China. Methods: Employees exposed to dust in enterprises of the Eighth Division located in the XPCC in 2023 were selected as the subjects of this cross-sectional study. Their lung ventilation function indicators were extracted from health examination records, and an on-site electronic questionnaire survey was conducted among them. Binary logistic regression analyses were conducted to evaluate the factors influencing lung ventilation function. Results: According to the fixed value criteria, the abnormal rates of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were 31.6, 1.4, and 0.4%, respectively. The lower limit of normal (LLN) criteria could overestimate the rate of abnormal lung ventilation function. Several factors were related to impaired lung ventilation function, including gender, age, education level, marital status, body mass index (BMI), smoking status, physical activity, the type of dust, industry, enterprise scale, occupation, length of service, working shift, monthly income, and respiratory protection. Conclusions: A relatively low abnormal rate of lung ventilation function was observed among employees exposed to dust in enterprises of the Eighth Division, XPCC, and their lung ventilation function was associated with various factors. Effective measures should be taken urgently to reduce the effects of adverse factors on lung ventilation function, thereby further protecting the health of the occupational population.


Assuntos
Poeira , Exposição Ocupacional , Humanos , China , Masculino , Feminino , Estudos Transversais , Adulto , Exposição Ocupacional/efeitos adversos , Pessoa de Meia-Idade , Inquéritos e Questionários , Testes de Função Respiratória , Ventilação Pulmonar/fisiologia , Capacidade Vital , Volume Expiratório Forçado
3.
Artigo em Inglês | MEDLINE | ID: mdl-38734935

RESUMO

Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.

4.
Cell Rep Med ; : 101519, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38692271

RESUMO

Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1ß and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.

5.
BMC Pulm Med ; 24(1): 220, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702679

RESUMO

BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica , Fumar , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Fumar/epidemiologia , Fumar/efeitos adversos , Periodontite/genética , Periodontite/epidemiologia , Índice de Gravidade de Doença , Predisposição Genética para Doença , Doenças Periodontais/genética , Doenças Periodontais/epidemiologia
6.
Carbohydr Polym ; 335: 122078, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616098

RESUMO

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.


Assuntos
Antibacterianos , Antioxidantes , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Transporte Biológico , Fermentação , Alimento Funcional
7.
Nat Commun ; 15(1): 3382, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643164

RESUMO

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Microambiente Tumoral , Organoides/patologia , Medicina de Precisão/métodos
8.
Am J Case Rep ; 25: e943801, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632857

RESUMO

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for severe aplastic anemia (SAA). It is known that SAA can evolve into malignant clonal diseases, such as acute myeloblastic leukemia (AML) or myelodysplastic syndrome. However, the transformation of SAA into AML after allo-HSCT is a rare phenomenon. Here, we report a case of SAA transformed into AML after patient received human leucocyte antigen (HLA)-matched sibling peripheral blood stem cell transplantation. CASE REPORT A 51-year-old female patient presented with petechiae and fatigue and received a diagnosis of idiopathic SAA. The immunosuppressive therapy combined with umbilical cord blood transplantation failed for this patient. Then, she received HLA-matched sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). However, 445 days after allo-PBSCT, the patient had a diagnosis of AML by bone marrow puncture. Donor-recipient chimerism monitoring and cytogenetic analysis confirmed that the leukemia was donor cell origin. Notably, a new HOXA11 mutation was detected in the peripheral blood of the patient after transplantation by whole-exome sequencing, which was the same gene mutation detected in the donor. The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission. However, the leukemia relapsed after 2 cycles of consolidation chemotherapy. Unfortunately, the patient died of leukemia progression 575 days after allo-HSCT. CONCLUSIONS The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Feminino , Humanos , Pessoa de Meia-Idade , Anemia Aplástica/terapia , Doadores de Tecidos , Leucemia Mieloide Aguda/terapia , Antígenos HLA
9.
Front Oncol ; 14: 1337035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638861

RESUMO

Objectives: Sessile serrated lesions (SSLs) are precursors of sporadic colorectal cancer (CRC) and have distinct characteristics compared with conventional adenomas (CAs). Several lifestyle and environmental factors may play critical roles in the development of advanced lesions. Our aim is to describe the features of SSLs and CAs and further explore risk factors for advanced lesions. Methods: This is an observational study that collected demographic, endoscopic, and histological data from the China-Japan Friendship Hospital among the inpatient population with pathologically reported as SSL or CA between 2015 and 2022. We analyzed the clinicopathology and endoscopic differences between SSL alone, CA alone, and synchronous SSL+CA groups, and identified risk factors using multiple regression analysis. Results: A total of 9236 polyps from 6598 patients were included in the cohort. Patients with SSL+CA were more likely to be older (p=0.008), while individuals with SSL alone had a higher proportion of early-onset polyps (p<0.001), and SSLs were more common in advanced polyps than CAs (p<0.001). A greater proportion of advanced polyps in the SSL and CA groups were diagnosed as Yamada III, Yamada IV, and laterally spreading tumor (p=0.002, p<0.001, respectively), and multiple SSLs and CAs were more represented in nonadvanced polyps than in advanced polyps. In multiple regression analysis, older patients were more likely to develop advanced SSLs (aOR 1.05, 95% CI 1.02-1.09, p=0.005). Conclusion: SSLs and CAs have diverse demographic, endoscopic, and histological characteristics, and their advanced lesions share different risk factors, which advances the understanding of the etiology and progression of SSLs.

10.
Toxicology ; 504: 153807, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38641160

RESUMO

Decabromodiphenyl ether (BDE209) has been demonstrated to be associated with thyroid dysfunction and thyroid carcinoma risk as a widely used brominated flame retardants. Although dabrafenib has been confirmed to be a promising therapeutic agent for papillary thyroid carcinoma (PTC) harboring BRAFV600E mutation, the rapid acquired dabrafenib resistance has brought a great challenge to clinical improvement and the underpinning mechanisms remain poorly defined. By treating PTC-derived and normal follicular epithelial cell lines with BDE209, we assessed its impact on the MAPK pathway's activation and evaluated the resultant effects on cell viability and signaling pathways, utilizing methods such as Western blot, IF staining, and RNA-seq bioinformatic analysis. Our findings reveal that BDE209 exacerbates MAPK activation, undermining dabrafenib's inhibitory effects by triggering the EGFR pathway, thereby highlighting BDE209's potential to diminish the pharmacological efficacy of dabrafenib in treating BRAF-mutated PTC. This research underscores the importance of considering environmental factors like BDE209 exposure in the effective management of thyroid carcinoma treatment strategies.


Assuntos
Receptores ErbB , Éteres Difenil Halogenados , Imidazóis , Mutação , Oximas , Proteínas Proto-Oncogênicas B-raf , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Éteres Difenil Halogenados/toxicidade , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia , Oximas/farmacologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Imidazóis/farmacologia , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Antineoplásicos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos
11.
Rev Neurosci ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38517315

RESUMO

Peripheral nerve injury (PNI) is one of the most serious causes of disability and loss of work capacity of younger individuals. Although PNS has a certain degree of regeneration, there are still challenges like disordered growth, neuroma formation, and incomplete regeneration. Regarding the management of PNI, conventional methods such as surgery, pharmacotherapy, and rehabilitative therapy. Treatment strategies vary depending on the severity of the injury. While for the long nerve defect, autologous nerve grafting is commonly recognized as the preferred surgical approach. Nevertheless, due to lack of donor sources, neurological deficits and the low regeneration efficiency of grafted nerves, nerve guide conduits (NGCs) are recognized as a future promising technology in recent years. This review provides a comprehensive overview of current treatments for PNI, and discusses NGCs from different perspectives, such as material, design, fabrication process, and composite function.

12.
Front Plant Sci ; 15: 1344733, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516665

RESUMO

Introduction: Phosphorus (P), which plays a vital role in plant growth, is continually added to soil to maximize biomass production, leading to excessive P accumulation and water eutrophication. Results: In this study, a pot experiment using a subtropical tobacco-growing soil fertilized with four P levels-no P, low P, medium P, and high P-was conducted and rhizosphere and bulk soils were analyzed. Results: P addition significantly increased tobacco biomass production (except under low P input) and total soil P and available P content (P<0.05), whereas total nitrogen content decreased in the rhizosphere soils, although this was only significant with medium P application. P fertilization also significantly altered the bacterial communities of rhizosphere soils (P<0.05), but those of bulk soils were unchanged (P>0.05). Moreover, a significant difference was found between rhizosphere soils with low (LR) and high (HR) P inputs (P<0.05). Additionally, compared with rhizosphere soils with no P (CKR), Shannon diversity showed a declining trend, which was significant with LR and HR (P<0.05), whereas an increasing tendency was observed for Chao1 diversity except in LR (P>0.05). Functional prediction revealed that P application significantly decreased the total P and N metabolism of microorganisms in rhizosphere soils (P<0.05). Discussion: Collectively, our results indicate that maintaining sustainable agricultural ecosystems under surplus P conditions requires more attention to be directed toward motivating the potential of soil functional microbes in P cycling, rather than just through continual P input.

13.
Int J Biol Macromol ; 265(Pt 1): 130713, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471612

RESUMO

Rapeseed-derived peptides (RPPs) can maintain the homeostasis of human blood glucose by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) and activating the calcium-sensing receptor (CaSR). However, these peptides are susceptible to hydrolysis in the gastrointestinal tract. To enhance the therapeutic potential of these peptides, we developed a chitosan/sodium alginate-based nanocarrier to encapsulate two RPP variants, rapeseed-derived cruciferin peptide (RCPP) and rapeseed-derived napin peptide (RNPP). A convenient three-channel device was employed to prepare chitosan (CS)/sodium alginate (ALG)-RPPs nanoparticles (CS/ALG-RPPs) at a ratio of 1:3:1 for CS, ALG, and RPPs. CS/ALG-RPPs possessed optimal encapsulation efficiencies of 90.7 % (CS/ALG-RNPP) and 91.4 % (CS/ALG-RCPP), with loading capacities of 15.38 % (CS/ALG-RNPP) and 16.63 % (CS/ALG-RCPP) at the specified ratios. The electrostatic association between CS and ALG was corroborated by zeta potential and near infrared analysis. 13C NMR analysis verified successful RPPs loading, with CS/ALG-RNPP displaying superior stability. Pharmacokinetics showed that both nanoparticles were sustained release and transported irregularly (0.43 < n < 0.85). Compared with the control group, CS/ALG-RPPs exhibited significantly increased glucose tolerance, serum GLP-1 (Glucagon-like peptide 1) content, and CaSR expression which play pivotal roles in glucose homeostasis (*p < 0.05). These findings proposed that CS/ALG-RPPs hold promise in achieving sustained release within the intestinal epithelium, thereby augmenting the therapeutic efficacy of targeted peptides.


Assuntos
Brassica napus , Quitosana , Nanopartículas , Humanos , Quitosana/química , Portadores de Fármacos/química , Preparações de Ação Retardada , Brassica napus/metabolismo , Alginatos/química , Nanopartículas/química , Glucose , Peptídeos
14.
Mol Nutr Food Res ; 68(7): e2300749, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38511225

RESUMO

SCOPE: Palmitoleic acid (POA) is an omega-7 monounsaturated fatty acid that has been suggested to improve metabolic disorders. However, it remains unclear whether gut microbiota plays a role in the amelioration of metabolic disorders by POA. This study aims to investigate the regulation of POA on metabolism, as well as systemic inflammation in HFD-fed mice from the perspective of serum metabolome and gut microbiome. METHODS AND RESULTS: Thirty-six C57BL/6 male mice are randomly assigned to either a normal chow diet containing 1.9% w/w lard or an HFD containing 20.68% w/w lard or 20.68% w/w sea buckthorn pulp oil for 16 weeks. The study finds that POA significantly attenuated hyperlipidemia, insulin resistance, and inflammation in HFD-fed mice. POA supplementation significantly alters the composition of serum metabolites, particularly lipid metabolites in the glycerophospholipid metabolism pathway. POA obviously increases the abundance of Bifidobacterium and decreases the abundance of Allobaculum. Importantly, the study finds that glycerophosphocholine mediates the effect of Bifidobacterium on LDL-C, sphingomyelin mediates the effect of Bifidobacterium on IL-6, and maslinic acid mediates the effect of Allobaculum on IL-6. CONCLUSION: The results suggest that exogenous POA can improve metabolic disorders and inflammation in HFD-fed mice, potentially by modulating the serum metabolome and gut microbiome.


Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Masculino , Animais , Camundongos , Interleucina-6 , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Ácidos Graxos Monoinsaturados/farmacologia , Firmicutes , Dieta Hiperlipídica/efeitos adversos
15.
J Glaucoma ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38506842

RESUMO

PRCIS: Gonioscopy-assisted Transluminal Trabeculotomy may be an effective first line surgery for decreasing intraocular pressure and medication burden in patients with uveitis-related ocular hypertension or glaucoma. PURPOSE: The purpose of the study is to determine the efficacy of Gonioscopy-assisted transluminal trabeculotomy (GATT) to lower the intraocular pressure (IOP) in uveitis-related ocular hypertension (OHT) or glaucoma. METHODS: Retrospective case series that included patients with uveitis-related OHT or glaucoma that underwent GATT with or without concomitant cataract extraction and intraocular lens implantation at two Canadian academic centres from July 2018 to May 2022. Primary outcomes were : complete (no medications) and qualified success (with medication), and failure defined as (1) IOP > 21mmHg with maximal medical therapy, (2) the need of additional glaucoma procedure, (3) loss of light perception secondary to glaucoma, (4) IOP < 6 mmHg for 3 months. RESULTS: Twenty-one eyes from 18 patients were included with a mean preoperative IOP of 26.2±7.3 mmHg on 4.3±0.7 classes of glaucoma drops. Average follow-up was 29.2±17.6 months and 76% of eyes (n=16) had reached at least 12 months of follow-up. At the 12 month follow-up visit, there was a significant decrease in average IOP by 9.9±7.9 mmHg (38%, P=0.005) and a decrease of 1.9 in glaucoma medication classes (P=0.002). Fourteen percent of eyes achieved complete success while 80% of eyes achieved qualified success. Six eyes failed (29%) and five patients (24%) required an additional glaucoma surgery. The most common postoperative complication was hyphema (n=9; 43%). CONCLUSION: This small case series suggests that GATT may be an effective first line surgery for decreasing IOP and medication burden in patients with uveitis-related OHT or glaucoma. Further studies with longer follow-up should be conducted to assess its long-term outcomes.

16.
Front Cell Dev Biol ; 12: 1344705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419843

RESUMO

Exosomes, extracellular vesicles secreted by cells, have garnered significant attention in recent years for their remarkable therapeutic potential. These nanoscale carriers can be harnessed for the targeted delivery of therapeutic agents, such as pharmaceuticals, proteins, and nucleic acids, across biological barriers. This versatile attribute of exosomes is a promising modality for precision medicine applications, notably in the realm of cancer therapy. However, despite their substantial therapeutic potential, exosomes still confront challenges tied to standardization and scalability that impede their practice in clinical applications. Moreover, heterogeneity in isolation methodologies and limited cargo loading mechanisms pose obstacles to ensuring consistent outcomes, thereby constraining their therapeutic utility. In contrast, exosomes exhibit a distinct advantage in cancer diagnosis, as they harbor specific signatures reflective of the tumor's genetic and proteomic profile. This characteristic endows them with the potential to serve as valuable liquid biopsies for non-invasive and real-time monitoring, making possible early cancer detection for the development of personalized treatment strategies. In this review, we provide an extensive evaluation of the advancements in exosome research, critically examining their advantages and limitations in the context of cancer therapy and early diagnosis. Furthermore, we present a curated overview of the most recent technological innovations utilizing exosomes, with a focus on enhancing the efficacy of early cancer detection.

17.
Mol Ther ; 32(3): 749-765, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38310356

RESUMO

Approximately 80%-90% of hepatocellular carcinomas (HCC) occur in a premalignant environment of fibrosis and abnormal extracellular matrix (ECM), highlighting an essential role of ECM in the tumorigenesis and progress of HCC. However, the determinants of ECM in HCC are poorly defined. Here, we show that nuclear receptor RORγ is highly expressed and amplified in HCC tumors. RORγ functions as an essential activator of the matrisome program via directly driving the expression of major ECM genes in HCC cells. Elevated RORγ increases fibronectin-1 deposition, cell-matrix adhesion, and collagen production, creating a favorable microenvironment to boost liver cancer metastasis. Moreover, RORγ antagonists effectively inhibit tumor growth and metastasis in multiple HCC xenografts and immune-intact models, and they effectively sensitize HCC tumors to sorafenib therapy in mice. Notably, elevated RORγ expression is associated with ECM remodeling and metastasis in patients with HCC. Taken together, we identify RORγ as a key player of ECM remodeling in HCC and as an attractive therapeutic target for advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Sorafenibe , Colágeno/metabolismo , Microambiente Tumoral
18.
BMC Musculoskelet Disord ; 25(1): 133, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347477

RESUMO

OBJECTIVE: The aim of the study was to investigate the 3.0 Tesla magnetic resonance imaging (MRI) features of Madelung's deformity. MATERIALS AND METHODS: The wrist MRI scans of 19 patients clinically diagnosed with Madelung's deformity and 20 patients without deformity were consecutively selected from Beijing Jishuitan Hospital between April 2019 and December 2022 for observation, in the case group and control group, respectively. Multiple linear regression was used to analyze the factors affecting tilting angle and width of central disc (CD, also termed as triangular fibrocartilage, the main component of triangular fibrocartilage complex), while the chi-square test was used to compare the occurrences of CD (radial) attachment displacement, VL, and RTL. p < 0.05 indicated statistical significance. RESULTS: Madelung's deformity significantly contributed to the tilting and thickening of the CD. In the case group, the tilting angle and thickness of CD were (51.46 ± 1.33)° and (0.23 ± 0.01) cm, respectively, which was statistically significant (p < 0.05); the radial attachment of the CD significantly shifted away from the distal articular surface level (χ2 = 39.00, p < 0.001), with a mean displacement of (0.97 ± 0.38) cm. Furthermore, the cases demonstrated abnormally developed Vickers ligament (χ2 = 35.19, p < 0.001) and radiotriquetral ligament (χ2 = 25.66, p < 0.001). CONCLUSION: MRI provides a notable advantage in diagnosing Madelung's deformity. Compared with the control group, patients with Madelung's deformity exhibited tilting and thickening of the CD. Additionally, the radial attachment of the CD was significantly shifted proximally with abnormal development of Vickers and radiotriquetral ligaments.


Assuntos
Transtornos do Crescimento , Osteocondrodisplasias , Rádio (Anatomia) , Ulna , Humanos , Radiografia , Imageamento por Ressonância Magnética , Articulação do Punho/diagnóstico por imagem
19.
Plant Physiol Biochem ; 208: 108448, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422578

RESUMO

Sucrose content is a key factor for the flavor of edible peanut, which determines the sweet taste of fresh peanut and also attribute to pleasant flavor of roasted peanut. To explore the genetic mechanism of the sucrose content in peanut, an F2 population was created by crossing the sweet cultivar Zhonghuatian 1 (ZHT1) with Nanyangbaipi (NYBP). A genomic region spanning 28.26 kb on chromosome A06 was identified for the sucrose content through genetic mapping, elucidating 47.5% phenotypic variance explained. As the sucrose content had a significantly negative correlation with the oil content, this region was also found to be related to the oil content explaining 37.2% of phenotype variation. In this region, Arahy.42CAD1 was characterized as the most likely candidate gene through a comprehensive analysis. The nuclear localization of Arahy.42CAD1 suggests its potential involvement in the regulation of gene expression for sucrose and oil contents in peanut. Transcriptome analysis of the developing seeds in both parents revealed that genes involved in glycolysis and triacylglycerol biosynthesis pathways were not significantly down-regulated in ZHT1, indicating that the sucrose accumulation was not attributed to the suppression of triacylglycerol biosynthesis. Based on the WGCNA analysis, Arahy.42CAD1 was co-expressed with the genes involved in vesicle transport and oil body assembly, suggesting that the sucrose accumulation may be caused by disruptions in TAG transportation or storage mechanisms. These findings offer new insights into the molecular mechanisms governing sucrose accumulation in peanut, and also provide a potential gene target for enhancing peanut flavor.


Assuntos
Arachis , Sacarose , Arachis/genética , Arachis/metabolismo , Sacarose/metabolismo , Perfilação da Expressão Gênica , Mapeamento Cromossômico , Triglicerídeos/metabolismo , Transcriptoma/genética , Sementes/genética , Sementes/metabolismo
20.
Talanta ; 272: 125750, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364559

RESUMO

Imidazoline-linked cationic covalent triazine framework (IM-iCTF) was facilely prepared through the Debus-Radziszewski reaction, involving 4,4',4''-(1,3,5-triazine-2,4,6-triyl)trianiline, formaldehyde and methylglyoxal. The IM-iCTF was applied as a sorbent for cartridge solid-phase extraction (SPE). It provided good adsorption performance for estrogen and estrogen mimics including bisphenol F, bisphenol A, 7ß-estradiol, bisphenol B and estrone. The adsorption isotherm, adsorption kinetic model, thermodynamic calculations and adsorption mechanism were investigated to reveal the adsorption behavior. The IM-iCTF was employed for the extraction of the estrogens and estrogen mimics from water, fish and shrimp (fish and shrimp samples were extracted with acetonitrile before the SPE). The analytes were then determined by high-performance liquid chromatography with diode array detection. The limits of detection were 0.008-0.05 ng mL-1 for water, 0.015-0.11 µg g-1 for fish, and 0.012-0.10 µg g-1 for shrimp samples. This research not only offers a new approach to construct cationic covalent triazine framework, but also provides a reliable strategy for the adsorption/enrichment trace level of organic pollutants.


Assuntos
Estrogênios , Triazinas , Animais , Triazinas/análise , Estrogênios/análise , Estradiol/análise , Estrona/análise , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida/métodos , Água/química , Adsorção , Limite de Detecção
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