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1.
Artigo em Inglês | MEDLINE | ID: mdl-38839034

RESUMO

BACKGROUND: Interoception represents perception of the internal bodily state which is closely associated with social/emotional processing and physical health in humans. Understanding the mechanism underlying interoceptive processing, particularly its modulation, is thus of great importance. Given overlap between oxytocinergic pathways and interoceptive signaling substrates in both peripheral visceral organs and the brain, intranasal oxytocin administration is a promising approach for modulating interoceptive processing. METHODS: In a double-blind, placebo-controlled, between-subject design, 72 healthy male participants performed a cardiac interoceptive task during electroencephalograph (EEG) and electrocardiograph (ECG) recording to examine whether intranasal administration of the neuropeptide oxytocin can modulate interoceptive processing. We also collected data in a resting state to examine whether we could replicate previous findings. RESULTS: Results showed that in the interoceptive task oxytocin increased interoceptive accuracy at the behavioral level which was paralleled by larger heartbeat-evoked potential amplitudes at frontocentral and central regions on the neural level. However, there were no significant effects of oxytocin on EEG or ECG during resting-state. CONCLUSIONS: These findings suggest that oxytocin may only have a facilitatory effect on interoceptive processing during task-based conditions. Our findings not only provide new insights into the modulation of interoceptive processing via targeting the oxytocinergic system but also provide proof of concept evidence for the therapeutic potential of intranasal oxytocin in mental disorders with dysfunctional interoception.

2.
Food Sci Nutr ; 12(6): 4110-4121, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873490

RESUMO

Among middle-aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle-aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007-2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake-related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non-osteoporosis group (p < .001). The lowest tertile category is then used to act as a reference category, and a higher dietary folic acid intake amount is observed to be positively related to lower odds for risk of osteoporosis. This trend is also not changed in adjustments for combinations of different covariates (p all < .05). Based on this, a dietary folic acid intake of 475.5 µg/day is identified as an optimal cutoff value for revealing osteoporosis. Collectively, this nationwide population-based study reveals that a higher daily dietary folic acid intake has potential protective effects on osteoporosis in middle-aged and older people.

3.
Imeta ; 3(1): e165, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868519

RESUMO

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

4.
J Integr Med ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38871592

RESUMO

BACKGROUND: Electroacupuncture is often used to treat insomnia. OBJECTIVE: To evaluate the efficacy and safety of electroacupuncture for insomnia. SEARCH STRATEGY: Databases including PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data and VIP Full-text e-Journals Database were searched up to January 15, 2023. INCLUSION CRITERIA: Randomized clinical trials were included if they compared the clinical efficacy and safety of electroacupuncture with sham acupuncture, no treatment or usual care (UC) and general acupuncture. DATA EXTRACTION AND ANALYSIS: The full texts of the studies were reviewed to remove ineligible literature. The extracted data included authors, publication year, diagnostic criteria, sample size, population characteristics, interventions and outcomes. The above steps were performed independently by two reviewers and the data were cross-checked. Stata15.0 software was used to analyze the extracted outcome data. For continuous data (Pittsburgh Sleep Quality Index [PSQI] score and Insomnia Severity Index score), weighted mean difference (WMD) was calculated and 95% confidence interval (CI) was reported when the same scale was applied. For dichotomous variables (clinical response rate and adverse events), a meta-analysis was performed using risk ratio (RR) as the effect indicator. RESULTS: Thirty-one trials with 2226 subjects were included. The meta-analysis suggested that electroacupuncture was more effective in improving insomnia compared with the control group (sham acupuncture, no treatment, UC and general acupuncture) (RR = 1.21; 95% CI: [1.16, 1.27]), significantly reducing the PSQI score in insomnia patients after treatment and at follow-up (WMD = -3.23; 95% CI: [-4.29, -2.17]; P < 0.001). There was no significant difference in the incidence of adverse events between the EA and control groups (sham acupuncture and no treatment or UC. RR = 1.48; 95% CI: [0.91, 2.40]; P = 0.117). In addition, the regression results revealed that receiving electroacupuncture for seven to nine weeks provided the best efficacy (P < 0.05). CONCLUSION: Electroacupuncture can significantly promote better sleep quality in insomnia patients and is suitable for the treatment of various types of insomnia. However, the articles included were single-center trials with small sample sizes, and some articles were of poor quality. Therefore, further research is still needed to confirm these findings. Please cite this article as: Xu HY, Wu LN, Zhang Y, Ba T, Zhao XF. Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis. J Integr Med. 2024; Epub ahead of print.

5.
Adv Sci (Weinh) ; : e2402884, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874086

RESUMO

The construction of large and complex supramolecular architectures through self-assembly is at the forefront of contemporary coordination chemistry. Notwithstanding great success in various systems using anionic bridges (e.g., O2- or S2-) or organic ligands (e.g., pyridine or carboxylate ligands), the assembly of large cyanide-bridged clusters with increasing nuclearity remains a formidable synthetic challenge. In this study, it is achieved in preparing two heterometallic cyanometallate clusters with unprecedented complexity, [Fe20Co20] (1) and [Fe12Co15] (2), by creating the "flexibility" through a versatile ligand of bis((1H-imidazol-4-yl)methylene)hydrazine (H2L) and low-coordinate cobalt. Complex 1 features a super-square array of four cyanide-bridged [Fe4Co4] cube subunits as the corners that are interconnected by four additional [FeCo] units, resulting in a torus-shaped architecture. Complex 2 contains a lantern-like core-shell cluster with a triple-helix kernel of [Co3L3] enveloped by a [Fe12Co12] shell. The combined structure analysis and mass spectrometry study reveal a hierarchical assembly mechanism, which sheds new light on constructing cyanometallate nanoclusters with atomic precision. Moreover, complex 1 undergoes a thermally induced electron-transfer-coupled spin transition (ETCST) between the diamagnetic {FeII LS(µ-CN)CoIII LS} and paramagnetic {FeIII LS(µ-CN)CoII HS} configurations (LS = low spin, HS = high spin) above room temperature, representing the largest molecule displaying electron transfer and spin transition characteristic.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38874521

RESUMO

AIMS: Mitochondrial dynamics in alveolar macrophages (AMs) are associated with sepsis-induced acute lung injury (ALI). In this study, we aimed to investigate whether changes in mitochondrial dynamics could alter the polarization of AMs in sepsis-induced ALI and to explore the regulatory mechanism of mitochondrial dynamics by focusing on SIRT3-induced optic atrophy protein 1 (OPA1) deacetylation. RESULTS: The AMs of sepsis-induced ALI showed imbalanced mitochondrial dynamics and polarization to the M1 macrophage phenotype. In sepsis, SIRT3 overexpression promotes mitochondrial dynamic equilibrium in AMs. However, 3TYP-specific inhibition of SIRT3 increased the mitochondrial dynamic imbalance and pro-inflammatory polarization of AMs and further aggravated sepsis-induced ALI. OPA1 is directly bound to and deacetylated by SIRT3 in AMs. In AMs of sepsis-induced ALI, SIRT3 protein expression was decreased and OPA1 acetylation was increased. OPA1 acetylation at the lysine 792 amino acid residue (OPA1-K792) promotes self-cleavage and is associated with an imbalance in mitochondrial dynamics. However, decreased acetylation of OPA1-K792 reversed the pro-inflammatory polarization of AMs and protected the barrier function of alveolar epithelial cells in sepsis-induced ALI. INNOVATION: Our study revealed for the first time the regulation of mitochondrial dynamics and AMs polarization by SIRT3-mediated deacetylation of OPA1 in sepsis-induced ALI, which may serve as an intervention target for precision therapy of the disease. CONCLUSIONS: Our data suggest that imbalanced mitochondrial dynamics promote pro-inflammatory polarization of AMs in sepsis-induced ALI, and that deacetylation of OPA1 mediated by SIRT3 improves mitochondrial dynamic equilibrium, thereby ameliorating lung injury.

8.
Acta Biomater ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838903

RESUMO

Limited success has been achieved in ferroptosis-induced cancer treatment due to the challenges related to low production of toxic reactive oxygen species (ROS) and inherent ROS resistance in cancer cells. To address this issue, a self-assembled nanodrug have been investigated that enhances ferroptosis therapy by increasing ROS production and reducing ROS inhibition. The nanodrug is constructed by allowing doxorubicin (DOX) to interact with Fe2+ through coordination interactions, forming a stable DOX-Fe2+ chelate, and this chelate further interacts with sorafenib (SRF), resulting in a stable and uniform nanoparticle. In tumor cells, overexpressed glutathione (GSH) triggers the disassembly of nanodrug, thereby activating the drug release. Interestingly, the released DOX not only activates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) to produce abundant H2O2 production for enhanced ROS production, but also acts as a chemotherapeutics agent, synergizing with ferroptosis. To enhance tumor selectivity and improve the blood clearance, the nanodrug is coated with a related cancer cell membrane, which enhances the selective inhibition of tumor growth and metastasis in a B16F10 mice model. Our findings provide valuable insights into the rational design of self-assembled nanodrug for enhanced ferroptosis therapy in cancer treatment. STATEMENT OF SIGNIFICANCE: Ferroptosis is a non-apoptotic form of cell death induced by the iron-regulated lipid peroxides (LPOs), offering a promising potential for effective and safe anti-cancer treatment. However, two significant challenges hinder its clinical application: 1) The easily oxidized nature of Fe2+ and the low concentration of H2O2 leads to a low efficiency of intracellular Fenton reaction, resulting in poor therapeutic efficacy; 2) The instinctive ROS resistance of cancer cells induce drug resistance. Therefore, we developed a simple and high-efficiency nanodrug composed of self-assembling by Fe2+ sources, H2O2 inducer and ROS resistance inhibitors. This nanodrug can effectively deliver the Fe2+ sources into tumor tissue, enhance intracellular concentration of H2O2, and reduce ROS resistance, achieving a high-efficiency, precise and safe ferroptosis therapy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38847932

RESUMO

OBJECTIVE: Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. METHODS: A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. RESULTS: EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. CONCLUSION: Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

10.
Pharmacoepidemiol Drug Saf ; 33(6): e5846, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825963

RESUMO

PURPOSE: Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture. METHODS: Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration. RESULTS: Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day. CONCLUSIONS: EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care.


Assuntos
Analgésicos , Registros Eletrônicos de Saúde , Fraturas do Quadril , Medicare , Instituições de Cuidados Especializados de Enfermagem , Humanos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Idoso , Masculino , Idoso de 80 Anos ou mais , Estados Unidos , Analgésicos/administração & dosagem , Instituições de Cuidados Especializados de Enfermagem/estatística & dados numéricos , Medicare/estatística & dados numéricos , Cuidados Semi-Intensivos/estatística & dados numéricos , Acetaminofen/administração & dosagem
11.
Sci Adv ; 10(23): eadk9996, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838152

RESUMO

Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (ED-sHDL) or chemically conjugated (CD-sHDL) DM1. We found that CD-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than ED-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving CD-sHDL, leading to a better efficacy and immune memory of CD-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 (CD-Lipo) showed lower immunotoxicity than those with entrapped drug (ED-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.


Assuntos
Nanopartículas , Animais , Nanopartículas/química , Camundongos , Linhagem Celular Tumoral , Humanos , Receptores Depuradores Classe B/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Lipoproteínas HDL/metabolismo , Portadores de Fármacos/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Lipossomos/química , Lipídeos/química
12.
ISA Trans ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38851925

RESUMO

Uncertainty can lead to jitter or overshoot in mechanical systems, necessitating the design of multiple constraints to stabilize them. This paper proposes a control structure based on the generalized Udwadia-Kalaba equation to address these constraints simultaneously. An uncertain dynamical model is developed, incorporating both equality and inequality constraints. By integrating diffeomorphism theory, a robust control strategy is designed to ensure compliance with these constraints. Utilizing the Lyapunov approach, the uniform boundedness and uniform ultimate boundedness of the dynamical system are demonstrated. Finally, the feasibility of the proposed control method is validated through its application to a belt conveyor system.

13.
Inflammation ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822951

RESUMO

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, inflammation and fibrosis play an important role in its progression. Histone lysine crotonylation (Kcr) was first identified as a new type of post-translational modification in 2011. In recent years, prominent progress has been made in the study of sodium crotonate (NaCr) and histone Kcr in kidney diseases. However, the effects of NaCr and NaCr-induced Kcr on DKD remain unclear. In this study, db/db mice and high glucose-induced human tubular epithelial cells (HK-2) were used respectively, and exogenous NaCr and crotonoyl-coenzyme A (Cr-CoA) as intervention reagents, histone Kcr and DKD-related indicators were detected. The results confirmed that NaCr had an antidiabetic effect and decreased blood glucose and serum lipid levels and alleviated renal function and DKD-related inflammatory and fibrotic damage. NaCr also induced histone Kcr and histone H3K18 crotonylation (H3K18cr). However, NaCr and Cr-CoA-induced histone Kcr and protective effects were reversed by inhibiting the activity of Acyl-CoA synthetase short-chain family member 2 (ACSS2) or histone acyltransferase P300 in vitro. In summary, our data reveal that NaCr may mitigate DKD via an antidiabetic effect as well as through ACSS2 and P300-induced histone Kcr, suggesting that Kcr may be the potential molecular mechanism and prevention target of DKD.

14.
Cell Commun Signal ; 22(1): 307, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831315

RESUMO

BACKGROUND: Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24's role in peripheral nociception remain unclear. METHODS: Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels). RESULTS: IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2. CONCLUSION: Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.


Assuntos
Canais de Cálcio Tipo T , Proteínas Quinases Dependentes de AMP Cíclico , Receptores de Interleucina , Células Receptoras Sensoriais , Transdução de Sinais , Gânglio Trigeminal , Quinases da Família src , Animais , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/genética , Quinases da Família src/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Gânglio Trigeminal/metabolismo , Masculino , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiologia , Receptores de Interleucina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Interleucinas/metabolismo
15.
Toxicol Appl Pharmacol ; 488: 116980, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823456

RESUMO

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU.


Assuntos
Células Dendríticas , Encefalomielite Autoimune Experimental , Camundongos Endogâmicos C57BL , Quercetina , Fator de Transcrição STAT4 , Células Th17 , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Animais , Quercetina/farmacologia , Fator de Transcrição STAT4/metabolismo , Feminino , Camundongos , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Diferenciação Celular/efeitos dos fármacos , Técnicas de Cocultura , Anti-Inflamatórios/farmacologia
16.
ACS Appl Bio Mater ; 7(6): 3900-3914, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38840339

RESUMO

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.


Assuntos
Ligas , Antibacterianos , Materiais Biocompatíveis , Escherichia coli , Raios Infravermelhos , Teste de Materiais , Nanoestruturas , Staphylococcus aureus , Propriedades de Superfície , Titânio , Titânio/química , Titânio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Ligas/química , Ligas/farmacologia , Escherichia coli/efeitos dos fármacos , Nanoestruturas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Animais , Camundongos , Osteogênese/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Proliferação de Células/efeitos dos fármacos , Osseointegração/efeitos dos fármacos
17.
Cancer Imaging ; 24(1): 74, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872150

RESUMO

BACKGROUND: To assess MRI-based morphological features in improving the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) for categorizing thyroid nodules. METHODS: A retrospective analysis was performed on 728 thyroid nodules (453 benign and 275 malignant) that postoperative pathology confirmed. Univariate and multivariate logistic regression analyses were used to find independent predictors of MRI morphological features in benign and malignant thyroid nodules. The improved method involved increasing the ACR-TIRADS level by one when there are independent predictors of MRI-based morphological features, whether individually or in combination, and conversely decreasing it by one. The study compared the performance of conventional ACR-TIRADS and different improved versions. RESULTS: Among the various MRI morphological features analyzed, restricted diffusion and reversed halo sign were determined to be significant independent risk factors for malignant thyroid nodules (OR = 45.1, 95% CI = 23.2-87.5, P < 0.001; OR = 38.0, 95% CI = 20.4-70.7, P < 0.001) and were subsequently included in the final assessment of performance. The areas under the receiver operating characteristic curves (AUCs) for both the conventional and four improved ACR-TIRADSs were 0.887 (95% CI: 0.861-0.909), 0.945 (95% CI: 0.926-0.961), 0.947 (95% CI: 0.928-0.962), 0.945 (95% CI: 0.926-0.961) and 0.951 (95% CI: 0.932-0.965), respectively. The unnecessary biopsy rates for the conventional and four improved ACR-TIRADSs were 62.8%, 30.0%, 27.1%, 26.8% and 29.1%, respectively, while the malignant missed diagnosis rates were 1.1%, 2.8%, 3.7%, 5.4% and 1.2%. CONCLUSIONS: MRI morphological features with ACR-TIRADS has improved diagnostic performance and reduce unnecessary biopsy rate while maintaining a low malignant missed diagnosis rate.


Assuntos
Imageamento por Ressonância Magnética , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Procedimentos Desnecessários/estatística & dados numéricos , Curva ROC , Adulto Jovem , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Adolescente , Biópsia
18.
J Aging Health ; : 8982643241259781, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881277

RESUMO

OBJECTIVES: To examine lifetime experiences of employment discrimination and their association with Black older adults' employment status and well-being. METHODS: We use data from the Health and Retirement Study's leave-behind questionnaire to characterize lifetime experiences of being unfairly fired, not hired, or not promoted among Black older adults (N = 2948) and test associations with labor force status at age 62, job satisfaction among those working, and depressive symptoms. RESULTS: Employment discrimination was commonly reported by Black older adults, especially among men and those with college educations. Employment discrimination was not associated with employment status at age 62 but was associated with job dissatisfaction (OR = 2.00, p = .001) and depressive symptoms (Beta = 0.34, p < .001). DISCUSSION: Findings suggest a negative association between employment discrimination at any point in the life course and Black older adults' well-being. Employment discrimination is an obstacle to healthy aging, yet improved discrimination survey items are needed to fully capture its impact on Black Americans.

19.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891834

RESUMO

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent hereditary disorder that affects the kidneys, characterized by the development of an excessive number of fluid-filled cysts of varying sizes in both kidneys. Along with the progression of ADPKD, these enlarged cysts displace normal kidney tissue, often accompanied by interstitial fibrosis and inflammation, and significantly impair renal function, leading to end-stage renal disease. Currently, the precise mechanisms underlying ADPKD remain elusive, and a definitive cure has yet to be discovered. This review delineates the epidemiology, pathological features, and clinical diagnostics of ADPKD or ADPKD-like disease across human populations, as well as companion animals and other domesticated species. A light has been shed on pivotal genes and biological pathways essential for preventing and managing ADPKD, which underscores the importance of cross-species research in addressing this complex condition. Treatment options are currently limited to Tolvaptan, dialysis, or surgical excision of large cysts. However, comparative studies of ADPKD across different species hold promise for unveiling novel insights and therapeutic strategies to combat this disease.


Assuntos
Rim Policístico Autossômico Dominante , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/terapia , Rim Policístico Autossômico Dominante/patologia , Humanos , Animais , Rim/patologia , Rim/metabolismo , Modelos Animais de Doenças
20.
Bioorg Chem ; 149: 107500, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38823310

RESUMO

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Receptor com Domínio Discoidina 1 , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Receptor com Domínio Discoidina 1/antagonistas & inibidores , Receptor com Domínio Discoidina 1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Animais , Estrutura Molecular , Camundongos , Descoberta de Drogas , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C
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