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1.
Dent Mater ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39117497

RESUMEN

OBJECTIVES: This study aimed to evaluate the effects of incorporating the 0-20 wt% tetrapod-shaped zinc oxide (tZnO) whiskers on the mechanical, antibacterial, and cytotoxic properties exhibited by experimental dual-cure resin composites. METHODS: Commercially obtained tZnO whiskers underwent surface modification using 3-methacryloxypropyltrimethoxysilane (γ-MPS). Subsequently, four groups of resin composites containing 0, 5, 10, and 20 wt% silanized tZnO along with barium borosilicate glass (BaBSG) fillers were fabricated while maintaining total filler loading at 60 wt%. Mechanical properties were examined utilizing specimens produced adhering to ISO 4049:2019 guidelines where applicable. Depth of cure was quantified immediately, while three-point flexural strength, flexural modulus, fracture toughness, Vickers hardness, compressive strength, and diametral tensile strength were assessed after 24 h of storage in 37 °C distilled water. Planktonic bacteria of Streptococcus mutans (S. mutans) were cultured and tested for antibacterial activity using disk diffusion and microbial anti-adhesion assays. Cytotoxicity was examined by preparing extracts from specimens in a cell culture medium and exposing stem cells from human exfoliated deciduous teeth (SHED) to serial dilutions of these extracts, then assessing cell viability and survival using CCK-8 assay and live/dead staining. RESULTS: Elevating tZnO loading yielded significant reductions in depth of cure, compressive (from 296.4 to 254.6 MPa), and diametral tensile strength (from 42.7 to 31.0 MPa), while flexural strength (91.3-94.1 MPa), flexural modulus (6.4-6.6 GPa), fracture toughness (0.96-1.04 MPa·m0.5), and Vickers hardness (36.5-37.4 kgf·mm-2) remained the same. Composites integrating tZnO displayed markedly enhanced antibacterial activity against S. mutans, based on anti-adhesion tests and live/dead staining. No cytotoxicity was observed for SHED treated with extracts from resin composites possessing up to 20 wt% tZnO whiskers. SIGNIFICANCE: This study demonstrates that incorporating up to 20 wt% silanized tZnO in place of traditional barium glass particles appreciably enhances dual-cure resin composite antibacterial function against S. mutans without compromising mechanical properties.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39127911

RESUMEN

OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. CONCLUSION: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.

3.
J Oral Biosci ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128823

RESUMEN

OBJECTIVES: Dental caries, or tooth decay, is an oral health issue worldwide. Oral healthcare researchers are considering how to develop safe and effective preventive measures and treatments for dental caries. This study evaluated the potential applications of Compound K and BTEX-K, a Compound K-rich red ginseng extract, for the prevention and treatment of dental caries. Moreover, this study briefly confirmed its inhibitory effect on inflammation, an important factor in dental health. METHODS: The amount of organic acids produced by bacteria in biofilm was determined using in vitro and in vivo assays. The ability of these extracts to promote tooth remineralization and microhardness was evaluated using an in vivo mouse assay. We evaluated their anti-inflammatory potential by inhibiting proinflammatory cytokine expression and lipopolysaccharide-induced nitrous oxide production in cell lines. RESULTS: Compound K (10-20 µg/mL) and BTEX-K (50-100 µg/mL) effectively inhibited the growth of Streptococcus mutans bacteria, demonstrating significant antibacterial properties. They can potentially prevent biofilm formation by reducing lactic acid production in the teeth. These compounds showed a strong ability to promote tooth remineralization and improve the microhardness of acid-producing bacteria. They also possess potent anti-inflammatory properties that downregulate proinflammatory cytokine (interleukin-6, interleukin-1ß, inducible nitric oxide synthase) expression, suppress nuclear factor-kappa B transcription factor activation (∼1.6 times), and reduce nitrous oxide production in lipopolysaccharide-induced RAW264.7 cells. CONCLUSIONS: Compounds K and BTEX-K may provide a novel approach to dental caries prevention as well as inflammation prevention and treatment.

4.
Alzheimers Dement ; 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39129223

RESUMEN

INTRODUCTION: The heritability of Alzheimer's disease (AD) is estimated to be 58%-79%. However, known genes can only partially explain the heritability. METHODS: Here, we conducted gene-based exome-wide association study (ExWAS) of rare variants and single-variant ExWAS of common variants, utilizing data of 54,569 clinically diagnosed/proxy AD and related dementia (ADRD) and 295,421 controls from the UK Biobank. RESULTS: Gene-based ExWAS identified 11 genes predicting a higher ADRD risk, including five novel ones, namely FRMD8, DDX1, DNMT3L, MORC1, and TGM2, along with six previously reported ones, SORL1, GRN, PSEN1, ABCA7, GBA, and ADAM10. Single-variant ExWAS identified two ADRD-associated novel genes, SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. The druggability evidence suggests that DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets. DISCUSSION: Our study contributes to the current body of evidence on the genetic etiology of ADRD. HIGHLIGHTS: Gene-based analyses of rare variants identified five novel genes for Alzheimer's disease and related dementia (ADRD), including FRMD8, DDX1, DNMT3L, MORC1, and TGM2. Single-variant analyses of common variants identified two novel genes for ADRD, including SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets.

5.
Medicine (Baltimore) ; 103(33): e39446, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39151495

RESUMEN

RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.


Asunto(s)
Anemia , Hipotiroidismo Congénito , Tiroxina , Talasemia alfa , Humanos , Femenino , Talasemia alfa/complicaciones , Talasemia alfa/diagnóstico , Hipotiroidismo Congénito/complicaciones , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Preescolar , Tiroxina/uso terapéutico , Anemia/etiología , Anemia/tratamiento farmacológico , Enfermedades Musculares/etiología , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/complicaciones
6.
Front Immunol ; 15: 1457636, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139558

RESUMEN

The liver is vulnerable to various hepatotoxins, including carbon tetrachloride (CCl4), which induces oxidative stress and apoptosis by producing reactive oxygen species (ROS) and activating the mitogen-activated protein kinase (MAPK) pathway. Cereblon (CRBN), a multifunctional protein implicated in various cellular processes, functions in the pathogenesis of various diseases; however, its function in liver injury remains unknown. We established a CRBN-knockout (KO) HepG2 cell line and examined its effect on CCl4-induced hepatocellular damage. CRBN-KO cells exhibited reduced sensitivity to CCl4-induced cytotoxicity, as evidenced by decreased levels of apoptosis markers, such as cleaved caspase-3, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. CRBN deficiency enhanced antioxidant defense, with increased superoxide dismutase activity and glutathione ratios (GSH/GSSG), as well as reduced pro-inflammatory cytokine expression. Mechanistically, the protective effects of CRBN deficiency appeared to involve the attenuation of the MAPK-mediated pathways, particularly through decreased phosphorylation of JNK and ERK. Overall, these results suggest the crucial role of CRBN in mediating the hepatocellular response to oxidative stress and inflammation triggered by CCl4 exposure, offering potential clinical implications for liver injury in a wide range of liver diseases.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Apoptosis , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Estrés Oxidativo , Humanos , Apoptosis/efectos de los fármacos , Células Hep G2 , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Estrés Oxidativo/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/deficiencia , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Especies Reactivas de Oxígeno/metabolismo
8.
Plants (Basel) ; 13(15)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39124220

RESUMEN

Foxtail millet (Setaria italica) is an important cereal crop with rich nutritional value. Distinctness, Uniformity, and Stability (DUS) are the prerequisites for the application of new variety rights for foxtail millet. In this study, we investigated 32 DUS test characteristics of 183 foxtail millet resources, studied their artificial selection trends, and identified the varieties that conform to breeding trends. The results indicated significant differences in terms of the means, ranges, and coefficients of variation for each characteristic. A correlation analysis was performed to determine the correlations between various DUS characteristics. A principal component analysis was conducted on 31 test characteristics to determine their primary characteristics. By plotting PC1 and PC2, all the germplasm resources could be clearly distinguished. The trends in foxtail millet breeding were identified through a differential analysis of the DUS test characteristics between the landrace and cultivated varieties. Based on these breeding trends, the optimal solution types for multiple evaluation indicators were determined; the weight allocation was calculated; and a specific TOPSIS algorithm was designed to establish a comprehensive multi-criteria decision-making model. Using this model, the breeding potential of foxtail millet germplasm resources were ranked. These findings provided important reference for foxtail millet breeding in the future.

9.
Chin Med ; 19(1): 108, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153974

RESUMEN

BACKGROUND: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis constitutes a pivotal response by surgical trauma, manifesting as a critical aspect of the acute stress reaction. This hyperactivity resulted in adverse surgical outcomes and is often associated with increased postoperative anxiety. Increased evidence suggests that Nesfatin-1 plays a crucial role in stress responses and stress-related psychiatric disorders. Electroacupuncture (EA) is widely used to alleviate stress responses and anxiety, although its mechanism of action remains unclear. This study aimed to assess the mechanisms by which hypothalamic Nesfatin-1 contribute to the alleviation of HPA axis hyperactivity and anxiety by EA. METHODS: Partial hepatectomy (HT) was performed to simulate surgical trauma, and EA was applied at Zusanli (ST36) and Sanyinjiao (SP6). The levels of hypothalamic Nesfatin-1, c-Fos, and corticotropin-releasing hormone (CRH) were detected, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were regarded as indicators of HPA axis activity. Anxiety levels were assessed through open field tests (OFT), elevated plus maze (EPM), and light-dark box tests (LDBT). To investigate the role of Nesfatin-1, its expression was modulated using stereotactic viral injections or plasmid transfections. Transcriptome sequencing was employed to explore the downstream signaling pathways of Nesfatin-1. Additionally, brain cannula implantation was performed to facilitate targeted drug administration. RESULTS: Our findings demonstrated that EA reduced the hypothalamic overexpression of CRH and Nesfatin-1, as well as serum levels of ACTH and CORT. Additionally, it alleviated anxiety-like behaviors resulting from surgical trauma. We observed that overexpression of Nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) triggered hyperactivity of the HPA axis and anxiety. Conversely, knocking down Nesfatin-1 in the PVN reversed these effects caused by surgical trauma. Transcriptome sequencing identified the extracellular regulated protein kinases (ERK)/cAMP-response element binding protein (CREB) pathway as a key mediator in the impacts of surgical trauma and EA on the hypothalamus. Both in vivo and in vitro studies showed that overexpression of Nesfatin-1 activated the ERK/CREB pathway. Furthermore, administering ERK or CREB inhibitors into the PVN mitigated HPA axis hyperactivity and anxiety-like behaviors induced by surgical trauma. Finally, EA was observed to decrease the phosphorylation levels of ERK and CREB in the PVN. CONCLUSION: EA alleviates HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma through inhibition of Nesfatin-1/ERK/CREB pathway in the hypothalamus.

11.
J Cogn Neurosci ; : 1-16, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39106162

RESUMEN

Crossing a spatial boundary such as a doorway plays an important role in the temporal organization of episodic memory. However, despite the wealth of evidence showing that visual boundary structures in scenes affect our representation of space, no studies have tested the possibility that they also function as event boundaries even without active navigation. In this study, we used a nonnavigational scene-based memory task that required participants to remember a sequence of objects moving to various baskets in a scene. In the boundary condition, there was a freestanding boundary in the middle of the room, low enough to see the rest of the room beyond it. We found that the additional boundary within the scene was sufficient to trigger a larger response in the cortical visual scene network, the hippocampus, and their coordinated activity. These results suggest that active navigation across a spatial boundary such as a doorway into another room is not necessary to form an event boundary and that a visual representation of boundaries is sufficient to influence the organization of a hippocampal episodic memory.

12.
Chem Soc Rev ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39091219

RESUMEN

Silicon-stereogenic chiral organosilanes have found increasing applications in synthetic chemistry, medicinal chemistry, and materials science. In this context, various asymmetric catalytic methods have been established for the diverse synthesis of silicon-stereogenic silanes. In particular, asymmetric organocatalysis is emerging as an important and complementary synthetic tool for the enantioselective construction of silicon-stereocenters, along with the rapid development of chiral-metal catalyzed protocols. Its advent provides a powerful platform to achieve functionalized silicon-stereogenic organosilanes with structural diversity, and should lead to great development in chiral organosilicon chemistry. In this Tutorial Review, we highlight these latest achievements from two aspects: desymmetrizations of prochiral tetraorganosilanes and dynamic kinetic asymmetric transformations of racemic organosilanes by employing five organocatalytic activation modes. The advantages, limitations and synthetic value of each protocol, as well as the synthetic opportunities still open for further exploration, are also discussed.

13.
Appl Clin Inform ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102866

RESUMEN

BACKGROUND: Multitasking, defined as performing two or more interventions simultaneously, increases the cognitive burden of clinicians. This may, in turn, lead to higher risk of medication and procedural errors. Time motion study (TMS) data for nurses in nursing homes revealed an extensive amount of multitasking while managing medications. Further investigation of multitasked nursing interventions will provide a foundation for optimizing medication management workflows. OBJECTIVES: Using a continuous observational TMS method, this study aimed to describe pairs of multitasked nursing interventions associated with medication management interventions, including preparing and administering medications, assessing medication effects, instructing on medications, and documenting medication administration. METHODS: An external nurse observer used 57 pre-defined Omaha System nursing interventions embedded within TimeCaT (version 3.9) TMS data recording software to collect observation data in a single nursing home. A total of 120 hours of time-stamped observation data from nine nurses was downloaded from TimeCaT and analyzed using descriptive and inferential statistics. RESULTS: The majority (74%) of medication management interventions were multitasked, resulting in 2,003 pairs of multitasked interventions. Of the 57 Omaha System nursing interventions, 35 were involved in these multitasking pairs. When nurses multitasked, the average duration of medication preparation was longer (non-multitasked: 81 seconds; multitasked: 162 seconds, p<0.05), while the average duration of medication administration record documentation was shorter (non-multitasked: 93 seconds; multitasked: 66 seconds, p<0.05). CONCLUSIONS: The findings reveal the complexity of medication management in nursing homes with numerous and diverse multitasking pairs. Findings provide a platform for in-depth study of medication management multitasking in the clinical context, and inform future efforts to create clinical and informatics solutions to optimize medication management workflow. This method may be also applied to examine medication management and multitasking in other clinical settings.

14.
Age Ageing ; 53(8)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39108220

RESUMEN

BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.


Asunto(s)
Demencia , Osteoartritis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Alzheimer/epidemiología , Demencia/epidemiología , Demencia Vascular/epidemiología , Demencia Vascular/diagnóstico , Incidencia , Modelos Lineales , Imagen por Resonancia Magnética , Osteoartritis/epidemiología , Osteoartritis/terapia , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Biobanco del Reino Unido , Reino Unido/epidemiología
15.
BMC Oral Health ; 24(1): 896, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103804

RESUMEN

OBJECTIVE: Early childhood caries has become a globally crucial oral health problem over the decades. Most studies have discussed the association between low birth weight and early childhood caries; however, studies focusing on high birth weight have been relatively limited. This study aimed to assess the impact of high birth weight on the incidence and severity of dental caries in 4-5-year-old children. SUBJECTS AND METHODS: Study subjects included 491 children from a birth cohort study at 4-5 years of age. Data on dental caries, prenatal and perinatal factors, and socio-demographic determinants were recorded. Logistic regression models adjusted for potential confounders were performed to analyze the data. Two-sided P-value < 0.05 was considered statistically significant. RESULTS: Of the 491 children, the prevalence of dental caries was 48.7%. High birth weight (≥ 4,000 g) was significantly associated with increased incidence of dental caries (OR, 2.000; CI 95% 1.062-3.765), and the relatively enhanced risk OR was further increased in subjects experiencing caries (dmft ≥ 3) (OR, 2.437; CI 95% 1.306-4.549) compared with the normal birth weight (2,500-3,999 g). CONCLUSIONS: High birth weight is a risk factor for early childhood caries. Particular attention should be paid to children with birth weight more than or equal to 4,000 g.


Asunto(s)
Peso al Nacer , Caries Dental , Humanos , Caries Dental/epidemiología , Preescolar , Femenino , Masculino , Estudios de Cohortes , Incidencia , Prevalencia , Factores de Riesgo , Cohorte de Nacimiento , Índice CPO , China/epidemiología
16.
Chemistry ; : e202402488, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120485

RESUMEN

We report an H-bond donor controlled diastereoselective switchable intramolecular aza-Henry reaction of ketimines derived from α-ketoesters and 2-(2-nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza-quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide-bearing quaternary ammonium salt C2 selectively give cis-adducts in up to 20:1 dr and 99% ee, the corresponding urea-bearing analogue C8 preferentially give trans-adducts in up to 20:1 dr and 99% ee.

17.
ACS Sens ; 9(7): 3581-3593, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38958530

RESUMEN

Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.


Asunto(s)
Carbocianinas , Rayos Infrarrojos , Mitocondrias , Imagen Óptica , Fototerapia , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Carbocianinas/química , Animales , Ratones , Humanos , Fototerapia/métodos , Colorantes Fluorescentes/química , Femenino , Ratones Endogámicos BALB C , Terapia Fototérmica/métodos , Línea Celular Tumoral , Dimerización
18.
Nat Commun ; 15(1): 5540, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956042

RESUMEN

Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.


Asunto(s)
Encéfalo , Secuenciación del Exoma , Hierro , Humanos , Hierro/metabolismo , Encéfalo/metabolismo , Masculino , Femenino , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Persona de Mediana Edad , Predisposición Genética a la Enfermedad/genética , Anciano , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Adulto , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo
19.
Front Cardiovasc Med ; 11: 1397701, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962087

RESUMEN

Objective: Leukocyte parameters are associated with cardiovascular diseases. The aim of the present study was to investigate the role of leukocyte parameters in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) with high thrombus burden (HTB). Methods: A total of 102 consecutive STEMI patients with HTB who underwent PPCI within 12 h from the onset of symptoms between June 2020 and September 2021 were enrolled in this study. In addition, 101 age- and sex-matched STEMI patients with low thrombus burden (LTB) who underwent PPCI within 12 h from the onset of symptoms were enrolled as controls. Leukocyte parameters, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), were calculated at the time of admission. Results: The value of NLR and MLR were significantly higher in the HTB group than in the LTB group (6.24 ± 4.87 vs. 4.65 ± 3.47, p = 0.008; 0.40 ± 0.27 vs. 0.33 ± 0.20, p = 0.038). A cutoff value of >5.38 for NLR had a sensitivity and specificity of 53.9% and 74.3%, respectively, and MLR >0.29 had a sensitivity and specificity of 60.8% and 55.4%, respectively, for determining the STEMI patients with HTB [area under the receiver operating characteristic curve (AUC): 0.603, 95% confidence interval (CI): 0.524-0.681, p = 0.012; AUC: 0.578, 95% CI: 0.499-0.656, p = 0.046]. There was no significant difference of all-cause mortality rate and major adverse cardiac events (MACEs) between the STEMI patients with HTB or with LTB (3.92% in HTB group vs. 2.97% in LTB group, p = 0.712; 10.78% in HTB group vs. 8.91% in LTB group, p = 0.215). Compared with the HTB patients in the low NLR group, C-reactive protein, baseline troponin I, baseline brain natriuretic peptide, and leukocyte parameters, such as white blood cell, neutrophil, lymphocyte, NLR, PLR, and MLR, were also significantly higher in the high NLR group in STEMI patients who underwent PPCI with HTB (18.94 ± 19.06 vs. 35.23 ± 52.83, p = 0.037; 10.99 ± 18.07 vs. 21.37 ± 19.64, p = 0.007; 199.39 ± 323.67 vs. 430.72 ± 683.59, p = 0.028; 11.55 ± 3.56 vs. 9.31 ± 2.54, p = 0.001; 9.77 ± 3.17 vs. 5.79 ± 1.97, p = 0.000; 1.16 ± 0.44 vs. 2.69 ± 1.23, p = 0.000; 9.37 ± 4.60 vs 1.31 ± 2.58, p = 0.000; 200.88 ± 89.90 vs. 97.47 ± 50.99, p = 0.000; 0.52 ± 0.29 vs. 0.26 ± 0.14, p = 0.000, respectively). MACEs and heart failure in the high NLR group were significantly higher than that in the low NLR group of STEMI patients who underwent PPCI with HTB (20.45% vs. 4.25%, p = 0.041; 10.91% vs. 2.13%, p = 0.038). Conclusion: The value of NLR and MLR were higher in STEMI patients who underwent PPCI with HTB. In STEMI patients who underwent PPCI with HTB, a raised NLR could effectively predict the occurrence of MACEs and heart failure.

20.
Sci Rep ; 14(1): 15277, 2024 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961128

RESUMEN

Dietary biomarkers in urine remain elusive when evaluating diet-induced oxidative stress and inflammation. In our previous study, we conducted a randomized controlled crossover trial to compare the short-term (4-weeks) effects of the balanced Korean diet (BKD) with Western diets, including the 2010 dietary guidelines for Americans (2010 DGA) and typical American diet (TAD), on various metabolic indices in obese Korean adults. Building on this work, the current research focuses on the impact of these dietary interventions on oxidative stress (d-ROMs and BAP) and inflammation (CRP, TNF-α, IL-6, IL-1ß, MCP-1) biomarkers in serum, and the concurrent urine metabolomes. Each dietary regimen was in silico and experimentally examined for their antioxidant levels using ABTS, DPPH, and FRAP assays, as well as total flavonoid (TFC) and total phenolic (TPC) contents. We assessed post-intervention variations in oxidative stress and inflammation biomarkers in serum, as well as the urine metabolite profiles for the participants (n = 48, average age: 41 years). Antioxidant contents and associated total antioxidant capacity (TAC) were significantly higher for the recommended diets (BKD and 2010 DGA) compared to TAD (p < 0.05). Butanol extracts from recommended diets (BKD and 2010 DGA) showed significantly higher antioxidant activity compared to TAD in ABTS (p < 0.01), DPPH, and FRAP (p < 0.05) assays. Consistent results were observed in total phenolic and flavonoid contents, mirroring their respective antioxidant activities. Following the intervention period, oxidative stress & inflammation markers in serum varied marginally, however, the urine metabolite profiles were clearly demarcated for the BKD and Western dietary groups (PC1 = 5.41%). For BKD group, the pre- and post-intervention urine metabolite profiles were clearly segregated (PLS2 = 2.93%). Compared to TAD, urine extracts from the recommended dietary group showed higher abundance of benzoic acid & phenolic derivatives (VIP > 0.7, p < 0.05). Metabolites associated with oxidative stress were observed higher in the urine samples from Western dietary groups compared to BKD. Urine metabolomics data delineated the post-intervention effects of three dietary interventions which corroborates the respective findings for their effects on metabolic indices.


Asunto(s)
Antioxidantes , Biomarcadores , Estudios Cruzados , Inflamación , Metabolómica , Estrés Oxidativo , Humanos , Adulto , Inflamación/dietoterapia , Inflamación/sangre , Masculino , Metabolómica/métodos , Femenino , Biomarcadores/orina , Biomarcadores/sangre , Antioxidantes/metabolismo , Antioxidantes/análisis , Persona de Mediana Edad , Metaboloma , Dieta Occidental
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