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1.
Med Decis Making ; : 272989X241263356, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39056320

RESUMO

BACKGROUND: Recent developments in causal inference and machine learning (ML) allow for the estimation of individualized treatment effects (ITEs), which reveal whether treatment effectiveness varies according to patients' observed covariates. ITEs can be used to stratify health policy decisions according to individual characteristics and potentially achieve greater population health. Little is known about the appropriateness of available ML methods for use in health technology assessment. METHODS: In this scoping review, we evaluate ML methods available for estimating ITEs, aiming to help practitioners assess their suitability in health technology assessment. We present a taxonomy of ML approaches, categorized by key challenges in health technology assessment using observational data, including handling time-varying confounding and time-to event data and quantifying uncertainty. RESULTS: We found a wide range of algorithms for simpler settings with baseline confounding and continuous or binary outcomes. Not many ML algorithms can handle time-varying or unobserved confounding, and at the time of writing, no ML algorithm was capable of estimating ITEs for time-to-event outcomes while accounting for time-varying confounding. Many of the ML algorithms that estimate ITEs in longitudinal settings do not formally quantify uncertainty around the point estimates. LIMITATIONS: This scoping review may not cover all relevant ML methods and algorithms as they are continuously evolving. CONCLUSIONS: Existing ML methods available for ITE estimation are limited in handling important challenges posed by observational data when used for cost-effectiveness analysis, such as time-to-event outcomes, time-varying and hidden confounding, or the need to estimate sampling uncertainty around the estimates. IMPLICATIONS: ML methods are promising but need further development before they can be used to estimate ITEs for health technology assessments. HIGHLIGHTS: Estimating individualized treatment effects (ITEs) using observational data and machine learning (ML) can support personalized treatment advice and help deliver more customized information on the effectiveness and cost-effectiveness of health technologies.ML methods for ITE estimation are mostly designed for handling confounding at baseline but not time-varying or unobserved confounding. The few models that account for time-varying confounding are designed for continuous or binary outcomes, not time-to-event outcomes.Not all ML methods for estimating ITEs can quantify the uncertainty of their predictions.Future work on developing ML that addresses the concerns summarized in this review is needed before these methods can be widely used in clinical and health technology assessment-like decision making.

2.
BMC Cancer ; 24(1): 875, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039511

RESUMO

BACKGROUND: The diagnosis of solitary pulmonary nodules has always been a difficult and important point in clinical research, especially granulomatous nodules (GNs) with lobulation and spiculation signs, which are easily misdiagnosed as malignant tumors. Therefore, in this study, we utilised a CT deep learning (DL) model to distinguish GNs with lobulation and spiculation signs from solid lung adenocarcinomas (LADCs), to improve the diagnostic accuracy of preoperative diagnosis. METHODS: 420 patients with pathologically confirmed GNs and LADCs from three medical institutions were retrospectively enrolled. The regions of interest in non-enhanced CT (NECT) and venous contrast-enhanced CT (VECT) were identified and labeled, and self-supervised labels were constructed. Cases from institution 1 were randomly divided into a training set (TS) and an internal validation set (IVS), and cases from institutions 2 and 3 were treated as an external validation set (EVS). Training and validation were performed using self-supervised transfer learning, and the results were compared with the radiologists' diagnoses. RESULTS: The DL model achieved good performance in distinguishing GNs and LADCs, with area under curve (AUC) values of 0.917, 0.876, and 0.896 in the IVS and 0.889, 0.879, and 0.881 in the EVS for NECT, VECT, and non-enhanced with venous contrast-enhanced CT (NEVECT) images, respectively. The AUCs of radiologists 1, 2, 3, and 4 were, respectively, 0.739, 0.783, 0.883, and 0.901 in the (IVS) and 0.760, 0.760, 0.841, and 0.844 in the EVS. CONCLUSIONS: A CT DL model showed great value for preoperative differentiation of GNs with lobulation and spiculation signs from solid LADCs, and its predictive performance was higher than that of radiologists.


Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Masculino , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/diagnóstico , Feminino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Diagnóstico Diferencial , Idoso , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/diagnóstico , Adulto , Granuloma/diagnóstico por imagem , Granuloma/patologia , Granuloma/diagnóstico
3.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3414-3420, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-39041113

RESUMO

Based on the systematic deconstruction of multi-dimensional and multi-target biological networks, modular pharmacology explains the complex mechanism of diseases and the interactions of multi-target drugs. It has made progress in the fields of pathogenesis of disease, biological basis of disease and traditional Chinese medicine(TCM) syndrome, pharmacological mechanism of multi-target herbs, compatibility of formulas, and discovery of new drug of TCM compound. However, the complexity of multi-omics data and biological networks brings challenges to the modular deconstruction and analysis of the drug networks. Here, we constructed the "Computing Platform for Modular Pharmacology" online analysis system, which can implement the function of network construction, module identification, module discriminant analysis, hub-module analysis, intra-module and inter-module relationship analysis, and topological visualization of network based on quantitative expression profiles and protein-protein interaction(PPI) data. This tool provides a powerful tool for the research on complex diseases and multi-target drug mechanisms by means of modular pharmacology. The platform may have broad range of application in disease modular identification and correlation mechanism, interpretation of scientific principles of TCM, analysis of complex mechanisms of TCM and formulas, and discovery of multi-target drugs.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Biologia Computacional/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Farmacologia/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos
4.
Anal Methods ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037195

RESUMO

Personalized medical diagnostics and monitoring have become increasingly important due to inefficient and delayed medical services of traditional centralized healthcare systems. To enhance the comfort and portability, flexible health monitoring systems have been developed in recent years. In particular, smart fiber/textile-based sensing devices show superiority for continuously monitoring personal health and vital physiological parameters owing to their light weight, good flexibility and inherent miniaturization. This review focuses on the recent advances in smart fiber/textile-based sensing devices for wearable electronic applications. First, fabrication strategies of smart sensing fibers/textiles are introduced in detail. In addition, sensing performances, working principles and applications of smart sensing fibers/textiles such as pressure sensing fibers/textiles, stretchable strain sensing fibers/textiles, temperature sensing fibers/textiles, and biofluid, gas and humidity sensing fibers/textiles in health monitoring are also reviewed systematically. Finally, we propose current challenges and future prospects in the area of fiber/textile-based sensors for wearable healthcare monitoring and diagnosis systems. In general, this review aims to give an overall perspective of the promising field by reviewing various fiber/textile-based sensing devices and highlighting the importance for researchers to keep up with the sequential exploration of soft sensing fibers/textiles for applications in wearable smart systems.

5.
Nanotechnology ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025082

RESUMO

Flexible, wearable triboelectric nanogenerators (TENGs) monitoring human movement and health signals have received more attention recently. In particular, developing a flexible TENG combining stress, strain, electrical output performance and durability becomes the current research focus. Herein, a highly stretchable, self-powered coaxial yarn TENGs were manufactured using a low-cost, efficient continuous wet-spinning method. Carbon nanotube/conductive thermoplastic polyurethane (MWCNT/CTPU) and polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) were utilized for the coaxial fibers conductive layers and dielectric layers, respectively. Fibers were continuously collected over a length of 10 m. Excellent electrical output with an open-circuit voltage (Voc) of 11.4 V, short-circuit current (Isc) of 114.8 nA, and short-circuit transfer charge (Qsc) of 6.1 nC was achieved. In addition, fabric TENGs with different two and three dimensional structures were further prepared by the developed coaxial fibers. The corresponding electrical output properties and practical performance were discussed. Results showed that the four-layer three-dimensional angle interlocking structure exhibited the optimal performance with an open-circuit voltage (Voc) of 38.4 V, short-circuit current (Isc) of 451.5 nA, and short-circuit transfer charge (Qsc) of 23.1 nC.

6.
Int J Cardiol ; 413: 132364, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39025135

RESUMO

BACKGROUND: Kawasaki disease (KD) is a kind of pediatric vasculitis, whose pathogenesis has not been elucidated until now. Many scholars believe that KD is one type of infectious diseases in the susceptible groups. However, no recognized pathogens are confirmed. Human cytomegalovirus (HCMV) is a ubiquitous human herpes virus, which can infect varieties of cells including endothelial cells. Studies reported that the viral protein pUL135 is very important for virus replication, reactivation and immune escape. Therefore, we hypothesize that HCMV pUL135 may have a pathogenic effect on KD. METHODS: We first determined pUL135 levels in the serum from KD patients. Next, we examined the effects and mechanisms of pUL135 on endothelial cell proliferation and migration. Finally, we assessed the effect of pUL135 on cardiac inflammation in a KD murine model. RESULTS: Data showed that pUL135 level was significantly increased in the serum from KD patients compared with the healthy and fever controls. And pUL135 expression in endothelial cells remarkably inhibited cell proliferation, migration and tube formation. Moreover, expression of pUL135 obviously affected actin cytoskeleton. Mechanism investigation substantiated that pUL135 mediated endothelial cell dysfunction via regulating CD2AP. Ultimately, we found that HCMV pUL135 aggravated coronary arteritis in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. CONCLUSION: Our findings imply that HCMV pUL135-mediated endothelial dysfunction plays an important role in exacerbating coronary artery injury in KD conditions.

7.
Nanomedicine (Lond) ; : 1-13, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016060

RESUMO

Aim: To evaluate a liposome complex conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for the treatment of pre-eclampsia (PE). Methods: In in vitro experiments, the transfection rate, silencing effect and cytotoxicity were determined. In the in vivo PE model, the siRNA distribution, mean arterial pressure, 24-h urine protein concentration, serum sFlt1 concentration, number of viable fetuses and placental weight were measured. Results: The nanomedicine effectively reduced the expression of sFIt1 and had a strong ability to target placental tissues. It could significantly reduce the symptoms of pre-eclampsia and improve pregnancy outcomes in PE model rats. Conclusion: The constructed nanomedicine can improve pregnancy outcomes in a rat model of pre-eclampsia and provides a new strategy for the treatment of pre-eclampsia.


[Box: see text].

8.
Environ Pollut ; 359: 124574, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39029865

RESUMO

Microalgae play an important role in aquatic ecosystems, but the widespread presence of micro- and nano-plastics (MNPs) poses significant threats to them. Haematococcus pluvialis is well-known for its ability to produce the antioxidant astaxanthin when it experiences stress from environmental conditions. Here we examined the effects of polystyrene nanoplastics (PS-NPs) at concentrations of 0.1, 1, and 10 mg/L on H. pluvialis over an 18-day period. Our results show that PS-NPs caused a significant, dose-dependent inhibition of H. pluvialis growth and a reduction in photosynthesis. Furthermore, PS-NPs severely damaged the morphology of H. pluvialis, leading to cell shrinkage, collapse, content release, and aggregation. Additionally, PS-NPs induced a dose-dependent increase in soluble protein content and a decrease in the production of extracellular polymeric substances. These findings indicate that PS-NPs has the potential to adversely affect both the physiology and morphology of H. pluvialis. An increase in reactive oxygen species and antioxidant enzyme activities was also observed, suggesting an oxidative stress response to PS-NPs exposure. Notably, the synthesis of astaxanthin, which is crucial for H. pluvialis's survival under stress, was significantly inhibited in a dose-dependent manner under strong light conditions, along with the down-regulation of genes involved in the astaxanthin biosynthesis pathway. This suggests that PS-NPs exposure reduces H. pluvialis's ability to survive under adverse conditions. This study enhances our understanding of the toxic effects of PS-NPs on microalgae and underscores the urgent need for measures to mitigate MNP pollution to protect aquatic ecosystems.

9.
Front Med (Lausanne) ; 11: 1389040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957305

RESUMO

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

10.
Ecotoxicol Environ Saf ; 282: 116703, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38986335

RESUMO

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

11.
Drug Des Devel Ther ; 18: 3005-3023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050796

RESUMO

Irisin is a muscle factor induced by exercise, generated through the proteolytic cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC-5). Numerous studies have shown that irisin plays a significant role in regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing systemic inflammatory responses, and providing neuroprotection. Additionally, irisin can exert immunomodulatory functions by regulating regulatory T cells (Tregs). Tregs are a highly differentiated subset of mature T cells that play a key role in maintaining self-immune homeostasis and are closely related to infections, inflammation, immune-related diseases, and tumors. Irisin exerts persistent positive effects on Treg cell functions through various mechanisms, including regulating Treg cell differentiation and proliferation, improving their function, modulating the balance of immune cells, increasing the production of anti-inflammatory cytokines, and enhancing metabolic functions, thereby helping to maintain immune homeostasis and prevent immune-related diseases. As an important myokine, irisin interacts with receptors on the cell membrane, activating multiple intracellular signaling pathways to regulate cell metabolism, proliferation, and function. Although the specific receptor for irisin has not been fully identified, integrins are considered potential receptors. Irisin activates various signaling pathways, including AMPK, MAPK, and PI3K/Akt, through integrin receptors, thereby exerting multiple biological effects. These research findings provide important clues for understanding the mechanisms of irisin's action and theoretical basis for its potential applications in metabolic diseases and immunomodulation. This article reviews the relationship between irisin and Tregs, as well as the research progress of irisin in immune-related diseases such as multiple sclerosis, myasthenia gravis, acquired immune deficiency syndrome, type 1 diabetes, sepsis, and rheumatoid arthritis. Studies have revealed that irisin plays an important role in immune regulation by improving the function of Tregs, suggesting its potential application value in the treatment of immune-related diseases.


Assuntos
Fibronectinas , Linfócitos T Reguladores , Humanos , Fibronectinas/metabolismo , Fibronectinas/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo
12.
Front Oncol ; 14: 1387345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055566

RESUMO

Lung cancer remains the leading cause of mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with a generally poor prognosis. In recent years, advances in targeted therapy and sequencing technology have brought significant improvement in the therapeutic outcomes of patients with advanced NSCLC. Targeted inhibitors directed against specific mutated or rearranged oncogenes, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and receptor tyrosine kinase ROS proto-oncogene 1(ROS1) among others, exhibit promising anti-tumor activity. Unfortunately, some patients develop acquired resistance and disease progression soon after initial remission. Despite the continuous development of new drugs and strategies to overcome drug resistance, it is still a major challenge in the treatment of NSCLC. The landscape of targeted therapy for NSCLC is evolving rapidly in response to the pace of scientific research. This study aimed to provide a comprehensive review of tumor target antigens and agents related to targeted therapy in NSCLC.

13.
Heliyon ; 10(13): e33788, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040345

RESUMO

The early stage of pancreatic cancer is asymptomatic and the treatment effect is not ideal. The progression to the advanced stage leads to a close relationship between mortality and morbidity. Therefore, there is an urgent need to develop precise and efficient therapeutic strategies to combat pancreatic cancer. In this study, we introduce a near-infrared (NIR) targeted drug delivery nanoparticle for ultrasound (US) imaging to guide magnetothermal/chemotherapy synergistic treatment of pancreatic cancer. Carboxylated polylactic acid (PLGA-PEG-COOH) serves as the structure of the nanoparticles, specifically binding the RGD cyclic peptide for pancreatic cancer targeting activity and promoting tumor aggregation of the nanoparticles. NIR-induced superparamagnetic iron oxide (SPIO) nanoparticles convert near-infrared light into thermal energy, triggering vaporization of perfluoropentane (PFH) droplets to generate PFH bubbles that enhance US imaging and help load doxorubicin (DOX), which are released from nanoparticles. SPIO can also be used for thermal ablation of tumors to improve therapeutic effect in treating pancreatic cancer. The results show that the targeted particles mediated by NIR have the characteristics of targeted drug delivery imaging. The microspheres exhibit strong acoustic and near-infrared responsiveness. Cell proliferation experiments showed that IR-mediated PFH-DOX@PLGA/SPIO-RGD NPs (RNPs) had a higher inhibitory effect on cell proliferation. Animal experiments have shown that RNPS can accumulate highly in the tumor area and show good therapeutic effect. In conclusion, this nanotherapeutic particle is a very promising targeted image-guided photothermal/chemotherapeutic synergistic tumor therapy strategy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39054959

RESUMO

The study aimed to explore the effect of the temperature chain management scheme on preventing hypothermia in patients undergoing robot-assisted radical prostatectomy (RARP). The patients were randomized to receive either intraoperative warming only (control group, Group C) or the temperature chain management (experimental group, Group T). We compared the core temperature, inadvertent perioperative hypothermia (IPH) rates, the incidence of shivering, and thermal comfort between the two groups. The perioperative core temperature of the Group T was higher than that of the Group C, and the incidence of IPH, the incidence of shivering in the postanesthesia care unit (PACU), and the length of stay in PACU were lower than those of the control group. The thermal comfort of Group T scored higher than that of Group C when leaving the PACU, all above have a statistically significant difference (p < 0.05). The temperature chain management scheme could decrease the IPH rates and reduce postoperative complications in RARP patients. The Clinical Trials Registration number is 2023IIT034.

15.
Colloids Surf B Biointerfaces ; 241: 114053, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38924849

RESUMO

The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn2+ produced by degradation can be used as a contrast agent for magnetic resonance (MR) imaging to provide visual exposure to tumor tissue. The released PTX can not only kill tumor cells directly, but also induce immunogenic death (ICD) of tumor cells, which can play a synergistic therapeutic effect with aPD-L1. Therefore, our study is expected to provide a promising strategy for improving the efficacy of cancer immunotherapy and the detection rate of cancer.


Assuntos
Glutationa , Imunoterapia , Imageamento por Ressonância Magnética , Neoplasias Ovarianas , Paclitaxel , Nanomedicina Teranóstica , Feminino , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Humanos , Imunoterapia/métodos , Concentração de Íons de Hidrogênio , Glutationa/química , Paclitaxel/farmacologia , Paclitaxel/química , Paclitaxel/administração & dosagem , Indóis/química , Indóis/farmacologia , Polímeros/química , Animais , Linhagem Celular Tumoral , Nanopartículas/química , Silício/química , Tamanho da Partícula , Propriedades de Superfície , Antígeno B7-H1/metabolismo , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos
17.
Chem Sci ; 15(23): 8946-8958, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38873054

RESUMO

The amyloid states of proteins are implicated in several neurodegenerative diseases and bioadhesion processes. However, the classical amyloid fibrillization mechanism fails to adequately explain the formation of polymorphic aggregates and their adhesion to various surfaces. Herein, we report a non-fibril amyloid aggregation pathway, with disulfide-bond-reduced lysozyme (R-Lyz) as a model protein under quasi-physiological conditions. Very different from classical fibrillization, this pathway begins with the air-water interface (AWI) accelerated oligomerization of unfolded full-length protein, resulting in unique plate-like oligomers with self-adaptive ability, which can adjust their conformations to match various interfaces such as the asymmetric AWI and amyloid-protein film surface. The pathway enables a stepwise packing of the plate-like oligomers into a 2D Janus nanofilm, exhibiting a divergent distribution of hydrophilic/hydrophobic residues on opposite sides of the nanofilm. The resulting Janus nanofilm possesses a top-level Young's modulus (8.3 ± 0.6 GPa) among amyloid-based materials and exhibits adhesive strength two times higher (145 ± 81 kPa) than that of barnacle cement. Furthermore, we found that such an interface-directed pathway exists in several amyloidogenic proteins with a similar self-adaptive 2D-aggregation process, including bovine serum albumin, insulin, fibrinogen, hemoglobin, lactoferrin, and ovalbumin. Thus, our findings on the non-fibril self-adaptive mechanism for amyloid aggregation may shed light on polymorphic amyloid assembly and their adhesions through an alternative pathway.

18.
Drug Des Devel Ther ; 18: 2215-2225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882049

RESUMO

Objective: While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health. Methods: Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions. Results: In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280-0.588; post-match: OR 0.385, 95% CI, 0.259-0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings. Conclusion: This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.


Assuntos
Hipertensão , Osteoporose , Espironolactona , Humanos , Espironolactona/uso terapêutico , Espironolactona/farmacologia , Espironolactona/efeitos adversos , Hipertensão/tratamento farmacológico , Osteoporose/tratamento farmacológico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Fraturas Ósseas/prevenção & controle , Fatores de Risco
19.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1123-1130, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38884247

RESUMO

China has complex natural conditions and is rich in biodiversity. Based on the geographical distribution and species composition of terrestrial mammals, we explored the characteristics and geographic partitioning of mammal populations in different regions of China. We used a clustering algorithm, combined with the spatial distribution data and taxonomic characteristics of mammals, to geographically partition the terrestrial mammals in China. We found 10 zoogeographic regions of terrestrial mammals in China: Northeast region, North China region, Eastern grassland region, Western region, Northwest region, Qiangtang plateau region, Eastern Qinghai-Tibet Plateau region, Himalayan region, South China region, and Taiwan-Hainan region. We found a new geographical zoning pattern for terrestrial mammals in China, examined the variability and characteristics of species composition among different regions, and quantified the association between species distribution and environmental factors. We proposed a method of incorporating taxonomic information into cluster analysis, which provided a new idea for zoogeographic region studies, a new perspective for understanding species diversity, and a scientific basis for animal conservation and habitat planning.


Assuntos
Biodiversidade , Ecossistema , Mamíferos , China , Animais , Mamíferos/classificação , Geografia , Análise por Conglomerados , Conservação dos Recursos Naturais
20.
Front Pharmacol ; 15: 1339153, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841368

RESUMO

Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, Tripterygium wilfordii poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.

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