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1.
Diabetol Metab Syndr ; 16(1): 232, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289758

RESUMEN

Diabetic cardiomyopathy (DCM) is a kind of myocardial disease that occurs in diabetes patients and cannot be explained by hypertensive heart disease, coronary atherosclerotic heart disease and other heart diseases. Its pathogenesis may be closely related to programmed cell death, oxidative stress, intestinal microbes and micro-RNAs. The excessive activation of mineralocorticoid receptors (MR) in DCM can cause damage to the heart and kidneys. The third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), finerenone, can effectively block MR, thus playing a role in protecting the heart and kidneys. This review mainly introduces the classification of MRA, and the mechanism of action, applications and limitations of finerenone in DCM, in order to provide reference for the study of treatment plans for DCM patients.

2.
Heliyon ; 10(17): e36283, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281567

RESUMEN

Homologous recombination defects (HRD) render cells fail to repair DNA double-strand break (DSB), which causes synthetic lethality in these cells with punch by poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Here, we reveal a receptor tyrosine kinase, AXL, whose inhibition leads to HRD in hepatocellular carcinoma (HCC) cells. AXL is upregulated in HCC tumors, which is positively correlated with low survival rates. AXL knockdown or AXL inhibition by bemcentinib reduces HR efficiency in HCC cells, and AXL plays its role in HR repair through its kinase activity. Furthermore, we find that AXL interacts with RPA2, enhancing the recruitment of RPA2 to DNA damage sites. Mechanistically, AXL promotes the tyrosinization of RPA2 at tyrosine 9, promoting the phosphorylation of CHK1, thereby strengthens the HR repair ability in HCC cells to resist DNA damage. In conclusion, our results reveal that AXL is a promising therapeutic biomarker for HCC patients, and present that targeting AXL-RPA2-CHK1 pathway together with PARP inhibitor will be effective therapeutic strategy in HCC.

3.
Curr Res Food Sci ; 9: 100830, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286428

RESUMEN

The World Health Organization (WHO) has identified the use of iron cookware as a potential strategy for alleviating iron deficiency anaemia (IDA) and emphasises the need for action-oriented research in this area. In response to this need, our study systematically investigated the patterns of iron release from various types of cookware under different cooking conditions. Among these, nitrided iron pots (NIPs), the most widely used cookware, were selected for the development of kinetic models to predict iron release efficiently across a range of cooking temperatures and pH levels in food materials. Our results demonstrated that iron release from the pots was significantly influenced by cooking conditions such as the type of cookware, cooking temperatures, cooking times, types of acidic substances, and the pH of the cooking environment. Specifically, higher temperatures, longer cooking times, lower pH levels, and the presence of acetic acid were found to maximise iron release into food. We developed a series of kinetic models-Iron Release-Temperature Models (I, II, and III) and Iron Release-pH Models (IV, V, and VI)-to predict iron release from NIPs. The temperature models are applicable for cooking food with a pH of 5.00-6.00 within a temperature range of 50-100 °C, while the pH models are designed for food with a pH of 3.00-6.00 at boiling temperatures. Validation experiments confirmed the relative accuracy of these models. Additionally, when comparing the predicted iron release with the Recommended Nutrient Intake (RNI) guidelines, the findings support the efficacy of iron pots as a viable method for iron supplementation.

4.
Heliyon ; 10(16): e36307, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39247310

RESUMEN

Objective: Carbon nanoparticle (CNP)-guided sentinel lymph node biopsy (SLNB) has been extensively adopted as a cost-effective and highly efficient method for tracing malignant tumors except for those associated with vulvar cancer. The current study aimed to validate the feasibility and efficacy of CNPs in tracking sentinel lymph nodes (SLNs) in patients with early vulvar cancer. Methods: We retrospectively reviewed patients with vulvar cancer at our institution from January 2016 to April 2022 who were pathologically diagnosed and underwent SLNB or inguinofemoral lymphadenectomy (IFLND). CNPs were the only lymphatic tracer used in SLNB. Patient demographics, perioperative outcomes and follow-up results, including overall survival (OS) and progression-free survival (PFS), were compared between the SLNB and IFLND groups. Results: Data from 52 patients were collected and investigated. Forty groins of 22 patients who underwent SLNB with CNP tracing were included. Black-stained SLNs were detected in 32 groins of 19 patients, and the rates of CNP detection by patient and by groin were 86.4 % and 80 %, respectively. Patients who underwent SLNB had better perioperative outcomes than those who underwent IFLND in certain aspects (groin drainage rate: 41.2 % and 80 %, respectively, p < 0.05; daily drainage volume (ml): 12.49 and 36.4, respectively, p < 0.05; and inguinal wound healing rate: 100 % and 80 %, respectively, p < 0.05). The results of survival analysis indicated similar prognoses for node-negative patients who underwent CNP-guided SLNB or IFLND. Conclusions: Sentinel lymph node mapping with CNPs in vulvar cancer is feasible and demonstrates considerable biosecurity. With a satisfactory SLN detection rate achieved expediently, CNPs are a promising lymphatic tracer worthy of further utilization in vulvar cancer and could be an alternative option to canonical tracers.

5.
Front Pharmacol ; 15: 1439036, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39221147

RESUMEN

Chitosan (CS) has been extensively studied in wound care for its intrinsic hemostatic and antibacterial properties. However, CS has limiting hemostasis applications on account of its drawbacks such as poor adhesion in humid environments and water solubility at neutral pH. CS-based biomaterials, inspired by mussel-adhesive proteins, serve as a suggested platform by biomedical science. The reports show that the mussel-inspired CS-based hemostatic structure has negligible toxicity and excellent adhesiveness. Biomedicine has witnessed significant progress in the development of these hemostatic materials. This review summarizes the methods for the modification of CS by mussel-inspired chemistry. Moreover, the general method for preparation of mussel-inspired CS-based biomaterials is briefly discussed in this review. This work is expected to give a better understanding of opportunities and challenges of the mussel-inspired strategy for the functionalization of CS-based biomaterials in hemostasis and wound healing. This review is hoped to provide an important perspective on the preparation of mussel-inspired CS-based hemostatic materials.

6.
Food Funct ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39257163

RESUMEN

Medium- and long-chain triglyceride (MLCT) is a striking structural lipid for the supply of energy and essential fatty free acids (FFAs) in the food field. This study aimed to prepare MLCT by enzymatic interesterification of rubber seed oil (RSO) and medium-chain triglyceride (MCT). Fortunately, the conversion of synthesized MLCT could reach 75.4% by the catalysis of Novozym 40086 (7 wt% to MCT) at a temperature of 40 °C with the substrate mole ratio of 1 : 0.7 (RSO : MCT). The as-synthesized MLCT contained unsaturated fatty acid (USFA, 50.13%) at the sn-2 position and exhibited superior performance on the acid value, peroxide value and iodine value in contrast to grade III soybean oil. Moreover, it exhibited the simultaneous release of LCFAs and MCFAs, extremely facilitating the reduction of body weight gain and control of the level of lipids in the blood. Finally, the preferred hepatic metabolism process of the obtained MLCT was proven to be the main cause of the reduced body weight and improved lipid levels by the in vivo deposition experiments. Therefore, our study suggested that the outstanding performance of the MLCT synthesized by RSO in foods as functional lipids.

7.
J Am Chem Soc ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264180

RESUMEN

α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of toxic cyanation reagents. Thus, the development of a greener and widely applicable method for the synthesis of aminonitriles from readily available starting materials presents an important yet unmet challenge. We developed a general and new method for the synthesis of aminonitriles from readily available aminoacetonitrile. This method utilized off-the-shelf ammonium salts as catalysts, tolerated air and moisture, and avoided the use of cyanation reagents, which rendered it a greener alternative to the widely practiced Strecker reaction approach. We further illustrated that chiral ammonium-catalyzed asymmetric reactions of N-arylidene aminoacetonitriles could provide chiral α-tertiary and α-quaternary aminonitriles and α-aminonitriles bearing two continuous stereocenters.

8.
Theranostics ; 14(13): 5102-5122, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267784

RESUMEN

Rationale: Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients. Methods: We performed whole-genome/exome sequencing (WGS/WES), Circle-Seq, single-molecule real-time (SMRT) long-read sequencing of circular DNA, and RNA sequencing (RNA-Seq) on 80 pairs of tumor and AT samples. We used our newly developed circular DNA analysis software, Circle-Map++ to detect small extrachromosomal circular DNA from Circle-Seq data. Results: We observed a high load and significant heterogeneity of extrachromosomal circular DNAs in UBC, including numerous single-locus and complex chimeric circular DNAs originating from different chromosomes. This includes highly chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. We also found that large tumor-specific extrachromosomal circular DNAs could influence genome-wide gene expression, and are detectable in time-matched urinary sediments. Additionally, we found that the extrachromosomal circular DNA correlates with hypermutation, copy number variation, oncogene amplification, and clinical outcome. Conclusions: Overall, our study provides a comprehensive extrachromosomal circular DNA map of UBC, along with valuable data resources and bioinformatics tools for future cancer and extrachromosomal circular DNA research.


Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Circular , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Humanos , ADN Circular/genética , Variaciones en el Número de Copia de ADN/genética , Secuenciación Completa del Genoma/métodos , Heterogeneidad Genética , Masculino , Femenino , Secuenciación del Exoma/métodos , Anciano , Mutación/genética
9.
Support Care Cancer ; 32(10): 630, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225814

RESUMEN

BACKGROUND: Detection of precachexia is important for the prevention and treatment of cachexia. However, how to identify precachexia is still a challenge. OBJECTIVE: This study aimed to detect cancer precachexia using a simple method and distinguish the different characteristics of precachexia and cachexia. METHODS: We included 3896 participants in this study. We used all baseline characteristics as input variables and trained machine learning (ML) models to calculate the importance of the variables. After filtering the variables based on their importance, the models were retrained. The best model was selected based on the receiver operating characteristic value. Subsequently, we used the same method and process to identify patients with precachexia in a noncachexia population using the same method and process. RESULTS: Participants in this study included 2228 men (57.2%) and 1668 women (42.8%), of whom 471 were diagnosed with precachexia, 1178 with cachexia, and the remainder with noncachexia. The most important characteristics of cachexia were eating changes, arm circumference, high-density lipoprotein (HDL) level, and C-reactive protein albumin ratio (CAR). The most important features distinguishing precachexia were eating changes, serum creatinine, HDL, handgrip strength, and CAR. The two logistic regression models for screening for cachexia and diagnosing precachexia had the highest area under the curve values of 0.830 and 0.701, respectively. Calibration and decision curves showed that the models had good accuracy. CONCLUSION: We developed two models for identifying precachexia and cachexia, which will help clinicians detect and diagnose precachexia.


Asunto(s)
Caquexia , Aprendizaje Automático , Neoplasias , Humanos , Caquexia/etiología , Caquexia/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias/complicaciones , Anciano , Estudios de Cohortes , Proteína C-Reactiva/análisis , Adulto
10.
Nanomaterials (Basel) ; 14(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39269051

RESUMEN

Quantum entanglement is essential in performing many quantum information tasks. Here, we theoretically investigate the stationary entanglement between a Laguerre-Gaussian (LG) cavity field and a rotating end mirror in an LG-cavity optorotational system with a nonlinear cross-Kerr (CK) interaction and a degenerate optical parametric amplifier (OPA). We calculate the logarithmic negativity of the system to quantify the stationary entanglement. We examine the influence of various system parameters such as the cavity detuning, the strength of the nonlinear CK interaction, the parametric gain and phase of the OPA, the power of the input Gaussian laser, the topological charge of the LG-cavity field, the mass of the rotating end mirror, and the ambient temperature on the stationary entanglement. Under the combined effect of the nonlinear CK interaction and the OPA, we find that the stationary entanglement can be substantially enhanced at lower Gaussian laser powers, smaller topological charges of the LG-cavity field, and larger masses of the rotating end mirror. We show that the combination of the nonlinear CK interaction and the OPA can make the stationary entanglement more robust against the ambient temperature.

11.
PhytoKeys ; 246: 179-187, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257485

RESUMEN

Salviapenghuana, a new species from Guizhou Province of southwestern China, is described and illustrated. Morphologically, Salviapenghuana is similar to S.filicifolia, but can be easily distinguished from the latter by ovate-lanceolate bracts, purple corolla, and foot-shaped fused lower arms of connective. In addition, S.penhuana is morphologically similar to S.cavaleriei, but differs by having 3-4-pinnate leave, ovate-lanceolate bracts, puberulent calyx, and longer upper arms of connective. Based on the fibril root, small calyx and corolla, and completely reduced posterior thecae, S.penghuana should be placed in section Sobiso of subg. Glutinaria.

12.
J Cardiothorac Surg ; 19(1): 521, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252031

RESUMEN

BACKGROUND: Selective antegrade cerebral perfusion (sACP) is a crucial cerebral protection technique employed during aortic dissection surgeries involving cardiopulmonary bypass. However, postoperative neurological complications, particularly those related to cannulation issues and perfusion problems, remain a significant concern. CASE PRESENTATION: This case report details an unusual instance where a 38-year-old male patient with Marfan syndrome experienced cerebral hypoperfusion during emergency surgery for Stanford Type A aortic dissection. Despite following standard protocols, a significant drop in regional cerebral oxygen saturation (rSO2) and abnormal blood pressure fluctuations were observed shortly after initiating sACP via the innominate artery. After initial attempts to optimize perfusion flow proved ineffective, the cannulation position was adjusted, leading to improvements. Nevertheless, the patient subsequently exhibited signs of cerebral hypoperfusion and was found to have suffered a new cerebral infarction. CONCLUSIONS: This case report underscores the importance of precise cannula placement during sACP procedures and the dire consequences that can arise from improper positioning. It emphasizes the need for continuous monitoring and prompt intervention in cases of abnormal cerebral oxygenation and blood pressure, as well as the value of considering cannulation-related issues as potential causes of postoperative neurological complications.


Asunto(s)
Disección Aórtica , Humanos , Masculino , Adulto , Disección Aórtica/cirugía , Cateterismo/métodos , Circulación Cerebrovascular/fisiología , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta/cirugía , Puente Cardiopulmonar/métodos , Puente Cardiopulmonar/efectos adversos , Síndrome de Marfan/complicaciones
13.
J Ethnopharmacol ; 335: 118680, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39117021

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a disease involving the enteric canal which is characterised by chronisch inflammatory reaction. Coptisine (COP), the distinctive component of Coptis chinensis Franch., is famous for its anti-inflammation, antioxidation, anti-bacteria, and anti-cancer. Earlier researches certified that COP is a prospective remedy for colitis, but the mechanism of colitis and the therapeutical target of COP are deficiently elucidated. AIM OF THIS STUDY: In this follow-up study, we adopted dextran sulfate sodium (DSS)-elicited UC model to further elucidate the possible mechanism of COP on UC in mice. MATERIALS AND METHODS: COP and the positive drug sulfasalazine (SASP) were administered by oral gavage in DSS-induced colitis mouse model. Oxidative stress, inflammatory cytokines, intestinal barrier permeability, protein expression of the TXNIP/NLRP3 inflammasome pathway and intestinal microbiome structure were assessed. RESULTS: Among this investigation, our team discovered that COP could mitigate DSS-elicited UC in murines, with prominent amelioration in weight loss, disease activity index, intestinal permeability (serum diamine oxidase and D-lactate), contracted colonal length and histologic alterations. Furthermore, COP greatly lowered the generation of pro-inflammatory factors, malondialdehyde (MDA) activity and reactive oxygen species (ROS) level, while increased superoxide dismutase (SOD) activity in colonal tissues. Additionally, COP downmodulated the proteic expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, IL-1ß and IL-18. Enteric microbiome sequencing displayed that DSS and COP tremendously influenced the constitution and diversity of enteric microbes in DSS-elicited UC murines. Besides, COP elevated the abundance of probiotic bacteria Bacteroidota, Akkermansia_muciniphila and Bacteroides_acidifaciens, lowered the proportions of potential pathogenic bacteria, such as Lachnospiraceae, Acetatifactor_muris, Clostridium_XlVa, Alistipes and Oscillibacter, and reduced the ratio of Bacillota/Bacteroidota, which vastly helped to reverse the enteric microbiome to a balanceable condition. Alterations in these bacteria were strongly correlated with the colitis relative index. CONCLUSION: The mechanism of COP against UC is connected with the suppression of TXNIP/NLRP3 inflammasome signalling pathway and the adjustment of the enteric microbiome profiles. The proofs offer new understandings upon the anti-UC function of COP, which might be a prospective candidate against UC.


Asunto(s)
Berberina , Proteínas Portadoras , Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , Inflamasomas , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Berberina/farmacología , Berberina/análogos & derivados , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Proteínas Portadoras/metabolismo , Ratones , Masculino , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Antiinflamatorios/farmacología , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad , Tiorredoxinas/metabolismo , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo
14.
J Environ Manage ; 368: 122217, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39146645

RESUMEN

The rapid increase in global plastic consumption, especially the worldwide use of polyethylene terephthalate (PET), has caused serious pollution problems. Due to the low recycling rate of PET, a substantial amount of waste accumulates in the environment, which prompts a growing focus on enzymatic degradation for its efficiency and environmentally friendliness. This study systematically designed and modified a cutinase, Est1 from Thermobifida alba AHK119, known for its potential of plastic-degradation at high temperatures. Additionally, the introduction of clustering algorithms provided the ability to understand and modify biomolecules, to accelerate the process of finding the optimal mutations. K-means was further proceeded based on the positive mutations. After comprehensive screening for thermostability and activity mutation sites, the dominant mutation Est1_5M (Est1 with the mutations of N213M, T215P, S115P, Q93A, and L91W) exhibited satisfying degradation ability for commercial PET bottles. The results showed that Est1_5M achieved a degradation rate of 90.84% in 72 h, 65-fold higher than the wild type. This study offers reliable theoretical and practical support for the development of efficient PET-degrading enzymes, providing a reference for plastic pollution management.


Asunto(s)
Hidrolasas de Éster Carboxílico , Tereftalatos Polietilenos , Tereftalatos Polietilenos/química , Hidrolasas de Éster Carboxílico/genética , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/química , Biodegradación Ambiental
15.
Nat Plants ; 10(9): 1317-1329, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39179701

RESUMEN

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is crucial for profiling histone modifications and transcription factor binding throughout the genome. However, its application in economically important plant organs (EIPOs) such as seeds, fruits and flowers is challenging due to their sturdy cell walls and complex constituents. Here we present advanced ChIP (aChIP), an optimized method that efficiently isolates chromatin from plant tissues while simultaneously removing cell walls and cellular constituents. aChIP precisely profiles histone modifications in all 14 tested EIPOs and identifies transcription factor and chromatin-modifying enzyme binding sites. In addition, aChIP enhances ChIP efficiency, revealing numerous novel modified sites compared with previous methods in vegetative tissues. aChIP reveals the histone modification landscape for rapeseed dry seeds, highlighting the intricate roles of chromatin dynamics during seed dormancy and germination. Altogether, aChIP is a powerful, efficient and sensitive approach for comprehensive chromatin profiling in virtually all plant tissues, especially in EIPOs.


Asunto(s)
Secuenciación de Inmunoprecipitación de Cromatina , Secuenciación de Inmunoprecipitación de Cromatina/métodos , Semillas/genética , Cromatina/metabolismo , Cromatina/genética , Frutas/genética , Inmunoprecipitación de Cromatina/métodos , Flores/genética , Código de Histonas
16.
Oncol Lett ; 28(4): 462, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39119233

RESUMEN

The importance of supraclavicular lymph node (SCLN) metastasis in cervical and upper thoracic esophageal squamous cell carcinoma (ESCC) has not been determined. The aim of the present study was to provide a detailed definition of the range of SCLN regions and to explore whether SCLNs should be considered as a regional lymph nodes for patients with cervical and upper thoracic ESCC. A retrospective analysis was performed on 230 patients with locally advanced cervical or upper thoracic ESCC who underwent radical radiotherapy and chemotherapy. The range of SCLN regions was defined in detail on contrast enhanced computed tomography images of the neck. According to whether the patient had lymph node metastasis in the supraclavicular region, the included patients were divided into two groups, and the survival differences and reasons for treatment failure between the two groups were analyzed. Of the 230 patients with ESCC, 71 (30.87%) exhibited lymph node metastases in the supraclavicular region. The median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 30 months, respectively (P<0.001). After propensity score matching (PSM), the median overall survival time of ESCC patients with and without SCLN metastasis was 17 and 28 months, respectively (P<0.001). During the follow-up period, there were a total of 101 cases of failure of treatment in the irradiation field, 6 cases had esophageal metastasis in the non-irradiated field and 27 cases had regional lymph node metastasis in the non-irradiated field. In addition, there were 33 cases of metastasis to the distant lymph nodes or organs. There was no significant difference in the local treatment failure rate between the groups with or without SCLN metastasis in both the irradiation field and the non-irradiation field, but the probability of distant metastasis in the SCLN metastasis group was significantly higher than that in the group without SCLN metastasis (P=0.025). In conclusion, patients with cervical and upper thoracic ESCC with SCLN metastasis have a poor prognosis and the median overall survival time is closer to that of metastatic ESCC than ESCC with regional lymph node metastasis; therefore, SCLNs should not be defined as regional lymph nodes in patients with cervical and upper thoracic ESCC.

17.
Asia Pac J Oncol Nurs ; 11(8): 100546, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39148936

RESUMEN

Objective: This study aimed to develop and validate a machine learning-based risk prediction model for catheter-related bloodstream infection (CRBSI) following implantation of totally implantable venous access ports (TIVAPs) in patients. Methods: A retrospective cohort study design was employed, utilizing the R software package mlr3. Various algorithms including logistic regression, naive Bayes, K nearest neighbor, classification tree, and random forest were applied. Addressing class imbalance, benchmarks were used, and model performance was assessed using the area under the curve (AUC). The final model, chosen for its superior performance, was interpreted using variable importance scores. Additionally, a nomogram was developed to calculate individualized risk probabilities, enhancing clinical utility. Results: The study involved 755 patients across both development and validation cohorts, with a TIVAP-CRBSI rate of 14.17%. The random forest model demonstrated the highest discrimination ability, achieving a validated AUC of 0.94, which was consistent in the validation cohort. Conclusions: This study successfully developed a robust predictive model for TIVAP-CRBSI risk post-implantation. Implementation of this model may aid healthcare providers in making informed decisions, thereby potentially improving patient outcomes.

18.
RSC Med Chem ; 15(8): 2601-2621, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39149100

RESUMEN

Diabetes mellitus is an exponentially growing chronic metabolic disease identified by prolonged hyperglycemia that leads to a plethora of health problems. It is well established that the skin of diabetic patients is more prone to injury, and hence, wound healing is an utmost critical restorative process for injured skin and other tissues. Diabetes patients have problems with wound healing at all stages, which ultimately results in delays in the healing process. Therefore, it is vital to find new medications or techniques to hasten the healing of wounds. Metal-organic frameworks (MOFs), an assorted class of porous hybrid materials comprising metal ions coordinated to organic ligands, can display great potential in accelerating diabetic wound healing due to their good physicochemical properties. The release of metal ions during the degradation of MOFs can promote the differentiation of fibroblasts into myofibroblasts and subsequently angiogenesis. Secondly, similar to enzyme-like active substances, they can eliminate reactive oxygen species (ROS) overproduction (secondary to the bio-load of wound bacteria), which is conducive to accelerating diabetic wound healing. Subsequently, MOFs can support the slow release of drugs (molecular or gas therapeutics) in diabetic wounds and promote wound healing by regulating pathological signaling pathways in the wound microenvironment or inhibiting the expression of inflammatory factors. In addition, the combination of photodynamic and photothermal therapies using photo-stimulated porphyrin-based MOF nanosystems has brought up a new idea for treating complicated diabetic wound microenvironments. In this review, recent advances affecting diabetic wound healing, current means of rapid diabetic wound healing, and the limitations of traditional approaches are discussed. Further, the diabetic wound healing applications of MOFs have been discussed followed by the future challenges and directions of MOF materials in diabetic wound healing.

19.
Adv Clin Exp Med ; 33(8): 889-899, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39194161

RESUMEN

BACKGROUND: T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses, but the functional role of Tfh cells in the pathogenesis of idiopathic membranous nephropathy (IMN) remains unclear. OBJECTIVES: This study aimed to establish a rat experimental membranous nephropathy model, investigate the phenotypic characteristics of Tfh cells, and analyze a clinically significant correlation between Tfh cells. MATERIAL AND METHODS: Passive Heymann nephritis (PHN) rats were induced by immunizing Sprague Dawley rats with anti-Fx1A serum. The frequency of Tfh and B cell subsets was analyzed with flow cytometry (FC). The serum concentration of interleukin-21 (IL-21), the relative mRNA expression levels of IL-21 and B cell lymphoma 6 (Bcl-6) in spleen mononuclear cells (MNCs), and the kidney infiltration of CD4+ T cells and IL-21 were assessed. The potential correlations among these measures were analyzed. RESULTS: In comparison with the control group, significantly increased percentages of Tfh cells, inducible T cell co-stimulator-positive (ICOS+) Tfh cells, and mRNA expression of Bcl-6 were detected in the spleen of PHN rats. Elevated IL-21 expression was detected in the serum and kidneys. Remarkably, the percentage of splenic ICOS+ Tfh cells was positively correlated with 24 h urine protein concentrations (r = 0.676, p = 0.011) in PHN rats. CONCLUSION: These data indicate that ICOS+ Tfh cells contribute to development of IMN, and they might be potential therapeutic targets for IMN.


Asunto(s)
Modelos Animales de Enfermedad , Progresión de la Enfermedad , Glomerulonefritis Membranosa , Interleucinas , Proteínas Proto-Oncogénicas c-bcl-6 , Ratas Sprague-Dawley , Células T Auxiliares Foliculares , Animales , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/sangre , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismo , Ratas , Interleucinas/sangre , Interleucinas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Masculino , Bazo/inmunología , Bazo/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo
20.
Med Eng Phys ; 130: 104205, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-39160029

RESUMEN

OBJECTIVES: Intimal tears caused by aortic dissection can weaken the arterial wall and lead to aortic aneurysms. However, the effect of different tear states on the blood flow behaviour remains complex. This study uses a novel approach that combines numerical haemodynamic simulation with in vitro experiments to elucidate the effect of arterial dissection rupture on the complex blood flow state within the abdominal aneurysm and the endogenous causes of end-organ malperfusion. MATERIALS AND METHODS: Based on the CT imaging data and clinical physiological parameters, the overall arterial models including aortic dissection and aneurysm with single tear and double tear were established, and the turbulence behaviours and haemodynamic characteristics of arterial dissection and aneurysm under different blood pressures were simulated by using non-Newtonian flow fluids with the pulsatile blood flow rate of the clinical patients as a cycle, and the results of the numerical simulation were verified by in vitro simulation experiments. RESULTS: Hemodynamic simulations revealed that the aneurysm and single-tear false lumen generated a maximum pressure of 320.591 mmHg, 267 % over the 120 mmHg criterion. The pressure differential generates reflux, leading to a WSS of 2247.9 Pa at the TL inlet and blood flow velocities of up to 6.41 m/s inducing extend of the inlet. DTD Medium FL instantaneous WP above 120 mmHg Standard 151 % Additionally, there was 82.5 % higher flow in the right iliac aorta than in the left iliac aorta, which triggered malperfusion. Thrombus was accumulated distal to the tear and turbulence. These results are consistent with the findings of the in vitro experiments. CONCLUSIONS: This study reveals the haemodynamic mechanisms by which aortic dissection induces aortic aneurysms to produce different risk states. This will contribute to in vitro simulation studies as a new fulcrum in the process of moving from numerical simulation to clinical trials.


Asunto(s)
Aorta Abdominal , Hemodinámica , Humanos , Aorta Abdominal/fisiopatología , Aorta Abdominal/diagnóstico por imagen , Rotura de la Aorta/fisiopatología , Rotura de la Aorta/diagnóstico por imagen , Disección Aórtica/fisiopatología , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Modelos Cardiovasculares
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