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1.
Proc Natl Acad Sci U S A ; 121(28): e2321193121, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38954549

RESUMEN

Iron antimonide (FeSb2) has been investigated for decades due to its puzzling electronic properties. It undergoes the temperature-controlled transition from an insulator to an ill-defined metal, with a cross-over from diamagnetism to paramagnetism. Extensive efforts have been made to uncover the underlying mechanism, but a consensus has yet to be reached. While macroscopic transport and magnetic measurements can be explained by different theoretical proposals, the essential spectroscopic evidence required to distinguish the physical origin is missing. In this paper, through the use of X-ray absorption spectroscopy and atomic multiplet simulations, we have observed the mixed spin states of 3d 6 configuration in FeSb2. Furthermore, we reveal that the enhancement of the conductivity, whether induced by temperature or doping, is characterized by populating the high-spin state from the low-spin state. Our work constitutes vital spectroscopic evidence that the electrical/magnetical transition in FeSb2 is directly associated with the spin-state excitation.

2.
Mol Ther ; 32(7): 2176-2189, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38734896

RESUMEN

The disassembly of the neuromuscular junction (NMJ) is an early event in amyotrophic lateral sclerosis (ALS), ultimately leading to motor dysfunction and lethal respiratory paralysis. The hexanucleotide GGGGCC repeat expansion in the C9orf72 gene is the most common genetic mutation, and the dipeptide repeat (DPR) proteins have been shown to cause neurodegeneration. While no drugs can treat ALS patients efficiently, new treatment strategies are urgently needed. Here, we report that a MuSK agonist antibody alleviates poly-PR-induced NMJ deficits in C9orf72-ALS mice. The HB9-PRF/F mice, which express poly-PR proteins in motor neurons, exhibited impaired motor behavior and NMJ deficits. Mechanistically, poly-PR proteins interacted with Agrin to disrupt the interaction between Agrin and Lrp4, leading to attenuated activation of MuSK. Treatment with a MuSK agonist antibody rescued NMJ deficits, and extended the lifespan of C9orf72-ALS mice. Moreover, impaired NMJ transmission was observed in C9orf72-ALS patients. These findings identify the mechanism by which poly-PR proteins attenuate MuSK activation and NMJ transmission, highlighting the potential of promoting MuSK activation with an agonist antibody as a therapeutic strategy to protect NMJ function and prolong the lifespan of ALS patients.


Asunto(s)
Esclerosis Amiotrófica Lateral , Proteína C9orf72 , Modelos Animales de Enfermedad , Unión Neuromuscular , Proteínas Tirosina Quinasas Receptoras , Animales , Unión Neuromuscular/metabolismo , Unión Neuromuscular/efectos de los fármacos , Ratones , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Humanos , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Longevidad/efectos de los fármacos , Neuronas Motoras/metabolismo , Neuronas Motoras/efectos de los fármacos , Agrina/metabolismo , Agrina/genética , Ratones Transgénicos , Anticuerpos/farmacología , Receptores Colinérgicos/metabolismo , Receptores Colinérgicos/genética , Proteínas Relacionadas con Receptor de LDL/metabolismo , Proteínas Relacionadas con Receptor de LDL/genética
3.
J Proteome Res ; 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39067049

RESUMEN

Although seminal plasma extracellular vesicles (SPEVs) play important roles in sperm function, little is known about their metabolite compositions and roles in sperm motility. Here, we performed metabolomics and proteomics analysis of boar SPEVs with high or low sperm motility to investigate specific biomarkers affecting sperm motility. In total, 140 proteins and 32 metabolites were obtained through differentially expressed analysis and weighted gene coexpression network analysis (WGCNA). Seven differentially expressed proteins (DEPs) (ADIRF, EPS8L1, PRCP, CD81, PTPRD, CSK, LOC100736569) and six differentially expressed metabolites (DEMs) (adenosine, beclomethasone, 1,2-benzenedicarboxylic acid, urea, 1-methyl-l-histidine, and palmitic acid) were also identified in WGCNA significant modules. Joint pathway analysis revealed that three DEPs (GART, ADCY7, and NTPCR) and two DEMs (urea and adenosine) were involved in purine metabolism. Our results suggested that there was significant correlation between proteins and metabolites, such as IL4I1 and urea (r = 0.86). Furthermore, we detected the expression level of GART, ADCY7, and CDC42 in sperm of two groups, which further verified the experimental results. This study revealed that several proteins and metabolites in SPEVs play important roles in sperm motility. Our results offered new insights into the complex mechanism of sperm motility and identified potential biomarkers for male reproductive diseases.

4.
BMC Genomics ; 25(1): 719, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054472

RESUMEN

BACKGROUND: Pigs serve as a crucial source of protein in the human diet and play a fundamental role in ensuring food security. However, infectious diseases caused by bacteria or viruses are a major threat to effective global pig farming, jeopardizing human health. Peripheral blood mononuclear cells (PBMCs) are a mixture of immune cells that play crucial roles in immunity and disease resistance in pigs. Previous studies on the gene expression regulation patterns of PBMCs have concentrated on a single immune stimulus or immune cell subpopulation, which has limited our comprehensive understanding of the mechanisms of the pig immune response. RESULTS: Here, we integrated and re-analyzed RNA-seq data published online for porcine PBMC stimulated by lipopolysaccharide (LPS), polyinosinic acid (PolyI:C), and various unknown microorganisms (EM). The results revealed that gene expression and its functional characterization are highly specific to the pathogen, identifying 603, 254, and 882 pathogen-specific genes and 38 shared genes, respectively. Notably, LPS and PolyI:C stimulation directly triggered inflammatory and immune-response pathways, while exposure to mixed microbes (EM) enhanced metabolic processes. These pathogen-specific genes were enriched in immune trait-associated quantitative trait loci (QTL) and eGenes in porcine immune tissues and were implicated in specific cell types. Furthermore, we discussed the roles of eQTLs rs3473322705 and rs1109431654 in regulating pathogen- and cell-specific genes CD300A and CD93, using cellular experiments. Additionally, by integrating genome-wide association studies datasets from 33 complex traits and diseases in humans, we found that pathogen-specific genes were significantly enriched for immune traits and metabolic diseases. CONCLUSIONS: We systematically analyzed the gene expression profiles of the three stimulations and demonstrated pathogen-specific and cell-specific gene regulation across different stimulations in porcine PBMCs. These findings enhance our understanding of shared and distinct regulatory mechanisms of genetic variants in pig immune traits.


Asunto(s)
Leucocitos Mononucleares , Lipopolisacáridos , Poli I-C , Sitios de Carácter Cuantitativo , Animales , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Porcinos , Poli I-C/farmacología , Lipopolisacáridos/farmacología , Perfilación de la Expresión Génica , Transcriptoma , Regulación de la Expresión Génica
5.
Cancer Sci ; 115(2): 427-438, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38115228

RESUMEN

Gastric cancer is one of the most common causes of cancer-related death worldwide. The N6 -methyladenosine (m6 A) reader IGF2BP1 (insulin-like growth factor-2 mRNA binding protein 1) has been reported to promote cancer progression by stabilizing oncogenic mRNAs through its m6 A-binding activity in some tumors. However, the role of IGF2BP1 in gastric carcinogenesis remains unclear. In this study, we found that IGF2BP1 is significantly downregulated in tumor tissues from patients with gastric cancer. Lower expression of IGF2BP1 is associated with poor prognosis. Gastric cancer cell proliferation is suppressed by IGF2BP1 in an m6 A-dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric cancer cells. Further m6 A sequencing and m6 A-RNA immunoprecipitation assays show that MYC (c-myc proto-oncogene) mRNA is a target transcript of IGF2BP1 in gastric cancer cells. IGF2BP1 inhibits gastric cancer cell proliferation by reducing the mRNA and protein expression of MYC. Mechanistically, IGF2BP1 promotes the degradation of MYC mRNA and inhibits its translation efficiency. Taken together, these data suggest that IGF2BP1 plays a tumor-suppressive role in gastric carcinogenesis by downregulating MYC in an m6 A-dependent manner, thereby making the IGF2BP1-MYC axis a potential target for gastric cancer treatment.


Asunto(s)
Neoplasias Gástricas , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Neoplasias Gástricas/genética
6.
Anal Chem ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017607

RESUMEN

A portable Hadamard-transform Raman spectrometer with excellent performance was fabricated consisting of a 785 nm laser, an optical filter, an optical system, a control system, and a signal processing system. As the core of the spectrometer, the optical system was composed of a slit, collimator, optical grating, reflector, digital micromirror devices (DMD), lens system, and InGaAs photodetector. Compared with a conventional dispersive Raman spectrometer, the proposed Raman spectrometer adopted the DMD and corresponding controlling device (DLPC350 control chip) to collect the Raman spectrum. Thus, in our design, the gratings are fixed, while the full Raman spectrum was collected by the deflection of the micromirror. This design can greatly improve the vibration resistance ability of the spectrometer since the gratings are not rotating during the spectrum collecting. More importantly, Hadamard-transform was used as signal processing technology, which has the ability of faster calculation, the merits of high energy input, single detector multichannel simultaneous detection (imaging) ability, and high signal-to-noise ratio (SNR). Hence, the Hadamard-transform portable Raman spectrometer has the potential to be applied in the field of point-of-care testing (POCT).

7.
Opt Express ; 32(7): 12291-12302, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571056

RESUMEN

We report a Ta2O5 photonic platform with a propagation loss of 0.49 dB/cm at 1550 nm, of 0.86 dB/cm at 780 nm, and of 3.76 dB/cm at 2000 nm. The thermal bistability measurement is conducted in the entire C-band for the first time to reveal the absorption loss of Ta2O5 waveguides, offering guidelines for further reduction of the waveguide loss. We also characterize the Ta2O5 waveguide temperature response, which shows favorable thermal stability. The fabrication process temperature is below 350°C, which is friendly to integration with active optoelectronic components.

8.
Langmuir ; 40(20): 10571-10579, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38725094

RESUMEN

In this work, polydopamine (PDA) and polyetheramine D230 were selected to construct the PDA-D230 interphase between the carbon fiber (CF) and epoxy matrix. Density functional theory (DFT) and molecular dynamics (MD) simulations were performed to explore the interface enhancement mechanisms of a carbon fiber reinforced polymer (CFRP) with the PDA-D230 interphase from the molecular level. The adsorption characteristics of a PDA molecule on the CF surface were investigated using the DFT method. The results show that stronger π-π stacking interactions are formed due to the structure and orientation preference of the PDA molecule. The interfacial structures and properties of CFRP with the PDA-D230 interphase are derived from MD simulations. The PDA-D230 interphase on the CF surface induces stronger interfacial interaction energy, leading to the better load transfer between the CF and epoxy matrix. The existence of the PDA-D230 interphase on the CF surface can decrease the mean-square displacement (MSD) value and the free volume fraction of CFRP, which restricts the movement of epoxy atoms and inhibits the translational and rotational motion of epoxy chains. Compared with the epoxy using pristine CFs as reinforcement, the interfacial shear stress (ISS) of CFRP with the PDA-D230 interphase is improved by 13.1%. Our results provide valuable insights into the interface characteristics of CFRP with the PDA-D230 interphase, which are of great significance for exploring the strengthening mechanisms for CFRPs with the PDA-D230 interphase.

9.
J Org Chem ; 89(15): 10467-10471, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39031914

RESUMEN

Full nitration is one of the most effective strategies used in synthesizing high-density energetic materials, but this strategy has reached its limit because the resultant compounds cannot be further functionalized. To overcome this limitation, we present the synergistic action of full nitration and strong intermolecular H-bonding in designing and synthesizing 1-trinitromethyl-3,5-dinitro-4-nitroaminopyrazole (DNTP) with a density that exceeds those of the reported monocyclic CHON compounds. The detonation velocity and specific impulse of DNTP exceed those of 1-trinitromethyl-3,4,5-trinitropyrazole (TTP), HMX, and ADN.

10.
Eur J Clin Microbiol Infect Dis ; 43(6): 1061-1072, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38536523

RESUMEN

INTENTION: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. METHODS: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. RESULTS: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). CONCLUSION: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glucocorticoides , Tuberculosis , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Masculino , Femenino , Anciano , Adulto , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Adulto Joven , Anciano de 80 o más Años , Adolescente , Tuberculosis/tratamiento farmacológico , Tuberculosis/complicaciones , China , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico
11.
Bioorg Med Chem ; 106: 117753, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38749342

RESUMEN

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.


Asunto(s)
Antígenos de Superficie , Diseño de Fármacos , Radioisótopos de Flúor , Tomografía de Emisión de Positrones , Radiofármacos , Animales , Humanos , Masculino , Radioisótopos de Flúor/química , Ratones , Antígenos de Superficie/metabolismo , Radiofármacos/síntesis química , Radiofármacos/química , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Estructura Molecular , Línea Celular Tumoral , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/metabolismo , Relación Estructura-Actividad
12.
Bioorg Med Chem ; 100: 117615, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38342079

RESUMEN

sTF (sialyl-Thomsen-Friedenreich) is a type of tumor-associated carbohydrate antigens (TACAs) and is highly expressed in various human malignancies. To validate if sTF could be a valuable molecular target for future cancer vaccine development, in this work the sTF antigen was prepared by adopting a strategy combining chemical and enzymatic methods, and then was covalently conjugated to a carrier protein, CRM197. The preliminary immunological evaluation, performed on BALB/c mice, revealed that the sTF-CRM197 conjugate elicited high titers of specific IgG antibodies. FACS experiments showed that the antisera induced by sTF-CRM197 conjugate could specifically recognize and bind to sTF-positive cancer cells T-47D. Furthermore, the conjugate mediated effective and specific antibody-mediated complement-dependent cytotoxicity (CDC).


Asunto(s)
Anticuerpos , Antígenos de Carbohidratos Asociados a Tumores , Animales , Ratones , Humanos , Antígenos de Carbohidratos Asociados a Tumores/química , Proteínas Bacterianas/química
13.
Bioorg Med Chem ; 100: 117631, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38330848

RESUMEN

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.


Asunto(s)
Leucemia Mieloide Aguda , Tirosina Quinasa 3 Similar a fms , Humanos , Apoptosis , Línea Celular Tumoral , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Piridinas/farmacología
14.
Dig Dis Sci ; 69(6): 2223-2234, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38594436

RESUMEN

BACKGROUND: Serum lactate, as a single and an easily available biomarker, has been applied in various diseases. AIMS: In this study, we aimed to explore the predictive value of serum lactate for short-term and long-term prognosis in acute pancreatitis (AP) admitted in intensive care unit (ICU) based on a large-scale database. METHODS: AP patients admitted in ICU in the MIMIC-IV database were included. We constructed three different models to investigate the relationships between serum lactate and clinical outcomes, including 30-day, 180-day and 1-year mortality in AP. Smooth fitting curves were performed for intuitively demonstrating the relationship between serum lactate and different outcomes in AP by the generalized additive model. RESULTS: A total of 895 AP patients admitted in ICU were included. The mortalities of 30 days, 180 days, and 1 year were 12.63% (n = 113), 16.87% (n = 151), and 17.54% (n = 157). In model B, with 1-mmol/L increment in serum lactate, the values of OR in 30-day, 180-day and 1-year mortality were 1.20 (95%CI 1.04-1.37, P = 0.0094), 1.21 (95%CI 1.06-1.37, P = 0.0039), and 1.21 (95%CI 1.07-1.38, P = 0.0035). The AUCs of serum lactate for predicting 30-day, 180-day, and 1-year mortality in AP were 0.688 (95%CI 0.633-0.743), 0.655 (95%CI 0.605-0.705), and 0.653 (95%CI 0.603-0.701), respectively. The cut-off value of serum lactate predicting 30-day, 180-day and 1-year mortality in AP was 2.4 mmol/L. CONCLUSION: Serum lactate could be an indicator for short-term and long-term mortality in patients with AP admitted in ICU.


Asunto(s)
Biomarcadores , Ácido Láctico , Pancreatitis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pancreatitis/mortalidad , Pancreatitis/sangre , Pancreatitis/diagnóstico , Ácido Láctico/sangre , Biomarcadores/sangre , Anciano , Adulto , Pronóstico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Tiempo , Valor Predictivo de las Pruebas , Enfermedad Aguda , Estudios Retrospectivos , Bases de Datos Factuales
15.
J Nanobiotechnology ; 22(1): 202, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658952

RESUMEN

Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.


Asunto(s)
Autofagia , Neoplasias Colorrectales , Reposicionamiento de Medicamentos , Ivermectina , Nanopartículas , Autofagia/efectos de los fármacos , Animales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/terapia , Humanos , Ratones , Nanopartículas/química , Ivermectina/farmacología , Ivermectina/química , Línea Celular Tumoral , Indoles/química , Indoles/farmacología , Ratones Endogámicos BALB C , Ratones Desnudos , Fotoquimioterapia/métodos , Antineoplásicos/farmacología , Antineoplásicos/química , Fototerapia/métodos , Ácido Hialurónico/química , Hidroxicloroquina/farmacología , Hidroxicloroquina/química , Terapia Fototérmica/métodos
16.
BMC Nephrol ; 25(1): 219, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982346

RESUMEN

BACKGROUND: Some studies have suggested that uric acid has antioxidant properties that can prevent bone loss, but the relationship between uric acid and bone mineral density is controversial. The aim of this study was to investigate the relationship between UA and BMD in patients with CKD stage 1-3. METHODS: We extracted 13,047 participants from the NHANES database, including 7342 male subjects and 5705 female subjects. Weighted multiple linear regression analysis was used to investigate the correlation between UA and BMD in patients with CKD stages 1-3. RESULTS: In patients with CKD stage 1-3, UA was significantly correlated with BMD. In the male group, UA was positively associated with BMD (ß, 7.94 [95%CI, 4.95, 10.94]). In the female group, there was a negative relationship between them (ß, -5.33 [95%CI, -8.77, -1.89]). The relationship between UA and BMD in male group showed an inverted U-shaped curve, and UA was positively correlated before 6.1 mg/dl and negatively correlated after 6.1 mg/dl. The relationship was basically negative in the female group. CONCLUSIONS: For the patients with CKD stage 1-3, the relationship between UA and BMD showed an inverted U-shaped curve in the males, while the relationship was largely negative in the females.


Asunto(s)
Densidad Ósea , Insuficiencia Renal Crónica , Ácido Úrico , Humanos , Ácido Úrico/sangre , Masculino , Femenino , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Anciano , Adulto , Encuestas Nutricionales
17.
BMC Pediatr ; 24(1): 498, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095721

RESUMEN

OBJECTIVE: To determine the prevalence of and risk factors for overweight and obese among Chinese children and adolescents. METHODS: This analytical cross-sectional study included 16,640 children and adolescents aged 6-18 years across four provinces of China in 2016. Physical characteristics and responses to questionnaires were analyzed. Body Mass Index (BMI) and the prevalence of overweight and obesity were calculated. RESULTS: Among children and adolescents, the overall prevalence of overweight and obesity in 2016 in four regions of China was 27.2% and 29.6%, respectively. Among different stages and sexes, the highest prevalence of obesity (15.8%) was observed in adolescent boys. From childhood to adolescence, the obesity rate among boys increased by 0.7% (from 15.1% to 15.8%), while the obesity rate among girls decreased by 0.9% (from 10.8% to 9.9%). Children and adolescents who were overweight or obese had significantly higher systolic blood pressures, larger waist circumferences and larger hip sizes than those with a normal BMI. Logistic regression analyses identified thirteen factors associated with overweight or obesity in children and adolescents. CONCLUSIONS: Our results indicate that the prevalence of overweight and obesity is high among children and adolescents, especially among male adolescents in four regions of China. A suitable intervention program should not only help parents understand the serious risk of childhood obesity but also, more importantly, help to encourage a healthy lifestyle among children and adolescents.


Asunto(s)
Índice de Masa Corporal , Obesidad Infantil , Humanos , Adolescente , China/epidemiología , Estudios Transversales , Masculino , Femenino , Niño , Obesidad Infantil/epidemiología , Prevalencia , Factores de Riesgo , Sobrepeso/epidemiología , Distribución por Sexo
18.
BMC Pediatr ; 24(1): 222, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561702

RESUMEN

BACKGROUND AND OBJECTIVES: To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors. METHODS: 3125 participants aged 10 ∼ 14 years were selected from China from the survey of "China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) ". Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators. RESULTS: In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P < 0.05 ), whereas LDL-C, vitamin D, and ferritin showed decreasing trends with the increase of age ( P < 0.05 ). The increase in hemoglobin and blood uric acid levels with age was more pronounced in males compared to females ( P < 0.05 ). BMI was positively correlated with blood glucose, hemoglobin, triglyceride, LDL-C, blood uric acid, serum creatinine, ferritin, transferrin receptor, hs-CRP, total protein, vitamin A ( P < 0.05 ). There was a significant BMI × age interaction in the correlation analysis with LDL-C, transferrin receptor, serum creatinine, and hs-CRP ( P < 0.05 ). BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and metabolic syndrome in all age groups ( OR > 1, P < 0.05 ). CONCLUSIONS: High BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and MetS in early adolescents. With the focus on energy intake beginning in early adolescence, the maintenance of a healthy weight warrants greater attention.


Asunto(s)
Hipertensión , Hipertrigliceridemia , Masculino , Femenino , Humanos , Adolescente , Índice de Masa Corporal , Proteína C-Reactiva/análisis , LDL-Colesterol , Ácido Úrico , Creatinina , Vitamina A , Hipertensión/epidemiología , Lipoproteínas HDL , Hemoglobinas/análisis , Ferritinas , Receptores de Transferrina
19.
Acta Radiol ; 65(6): 554-564, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38623640

RESUMEN

BACKGROUND: Computed tomography (CT) radiomics combined with deep transfer learning was used to identify cholesterol and adenomatous gallbladder polyps that have not been well evaluated before surgery. PURPOSE: To investigate the potential of various machine learning models, incorporating radiomics and deep transfer learning, in predicting the nature of cholesterol and adenomatous gallbladder polyps. MATERIAL AND METHODS: A retrospective analysis was conducted on clinical and imaging data from 100 patients with cholesterol or adenomatous polyps confirmed by surgery and pathology at our hospital between September 2015 and February 2023. Preoperative contrast-enhanced CT radiomics combined with deep learning features were utilized, and t-tests and least absolute shrinkage and selection operator (LASSO) cross-validation were employed for feature selection. Subsequently, 11 machine learning algorithms were utilized to construct prediction models, and the area under the ROC curve (AUC), accuracy, and F1 measure were used to assess model performance, which was validated in a validation group. RESULTS: The Logistic algorithm demonstrated the most effective prediction in identifying polyp properties based on 10 radiomics combined with deep learning features, achieving the highest AUC (0.85 in the validation group, 95% confidence interval = 0.68-1.0). In addition, the accuracy (0.83 in the validation group) and F1 measure (0.76 in the validation group) also indicated strong performance. CONCLUSION: The machine learning radiomics combined with deep learning model based on enhanced CT proves valuable in predicting the characteristics of cholesterol and adenomatous gallbladder polyps. This approach provides a more reliable basis for preoperative diagnosis and treatment of these conditions.


Asunto(s)
Aprendizaje Profundo , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Adulto , Pólipos/diagnóstico por imagen , Colesterol , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Valor Predictivo de las Pruebas , Pólipos Adenomatosos/diagnóstico por imagen , Aprendizaje Automático , Medios de Contraste , Radiómica
20.
Artículo en Inglés | MEDLINE | ID: mdl-38978504

RESUMEN

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis reveals significant enrichment of genes related to autophagy-related signaling pathways, including the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the mTOR signaling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examine the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviates the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). The findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.

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