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1.
Plants (Basel) ; 13(9)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38732492

RESUMEN

Tomato yellow leaf curl virus (TYLCV) is a prominent viral pathogen that adversely affects tomato plants. Effective strategies for mitigating the impact of TYLCV include isolating tomato plants from the whitefly, which is the vector of the virus, and utilizing transgenic lines that are resistant to the virus. In our preliminary investigations, we observed that the use of growth retardants increased the rate of TYLCV infection and intensified the damage to the tomato plants, suggesting a potential involvement of gibberellic acid (GA) in the conferring of resistance to TYLCV. In this study, we employed an infectious clone of TYLCV to inoculate tomato plants, which resulted in leaf curling and growth inhibition. Remarkably, this inoculation also led to the accumulation of GA3 and several other phytohormones. Subsequent treatment with GA3 effectively alleviated the TYLCV-induced leaf curling and growth inhibition, reduced TYLCV abundance in the leaves, enhanced the activity of antioxidant enzymes, and lowered the reactive oxygen species (ROS) levels in the leaves. Conversely, the treatment with PP333 exacerbated TYLCV-induced leaf curling and growth suppression, increased TYLCV abundance, decreased antioxidant enzyme activity, and elevated ROS levels in the leaves. The analysis of the gene expression profiles revealed that GA3 up-regulated the genes associated with disease resistance, such as WRKYs, NACs, MYBs, Cyt P450s, and ERFs, while it down-regulated the DELLA protein, a key agent in GA signaling. In contrast, PP333 induced gene expression changes that were the opposite of those caused by the GA3 treatment. These findings suggest that GA plays an essential role in the tomato's defense response against TYLCV and acts as a positive regulator of ROS scavenging and the expression of resistance-related genes.

2.
MMWR Morb Mortal Wkly Rep ; 73(16): 372-376, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662678

RESUMEN

HIV transmitted through cosmetic injection services via contaminated blood has not been previously documented. During summer 2018, the New Mexico Department of Health (NMDOH) was notified of a diagnosis of HIV infection in a woman with no known HIV risk factors who reported exposure to needles from cosmetic platelet-rich plasma microneedling facials (vampire facials) received at a spa in spring 2018. An investigation of the spa's services began in summer 2018, and NMDOH and CDC identified four former spa clients, and one sexual partner of a spa client, all of whom received HIV infection diagnoses during 2018-2023, despite low reported behavioral risks associated with HIV acquisition. Nucleotide sequence analysis revealed highly similar HIV strains among all cases. Although transmission of HIV via unsterile injection practices is a known risk, determining novel routes of HIV transmission among persons with no known HIV risk factors is important. This investigation identified an HIV cluster associated with receipt of cosmetic injection services at an unlicensed facility that did not follow recommended infection control procedures or maintain client records. Requiring adequate infection control practices and maintenance of client records at spa facilities offering cosmetic injection services can help prevent the transmission of HIV and other bloodborne pathogens and ensure adequate traceback and notification in the event of adverse clinical outcomes, respectively.


Asunto(s)
Infecciones por VIH , Plasma Rico en Plaquetas , Humanos , Infecciones por VIH/transmisión , Infecciones por VIH/epidemiología , Femenino , New Mexico/epidemiología , Adulto , Masculino , Persona de Mediana Edad , Técnicas Cosméticas , Agujas , Cara , Inducción Percutánea del Colágeno
3.
Virus Evol ; 10(1): veae015, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38510920

RESUMEN

We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase (pol) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02_AG (2.5 per cent) and CRF02_AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02_AG/B (24.3 per cent), B/CRF02_AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02_AG-like and CRF02_AG/B, an eighteen-member CRF02_AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02_AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02_AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02_AG, and CRF02_AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02_AG; B and CRF02_AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread.

5.
Bioorg Chem ; 144: 107110, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38224636

RESUMEN

Wet age-related macular degeneration (w-AMD) is one of the leading causes of vision loss in industrialized countries. A large body of evidence suggests that inhibitors targeting VEGFR2 may be effective in the treatment of w-AMD. The identification of an oral VEGFR2 inhibitor for the treatment of w-AMD provides an opportunity for a route of administration other than intravitreal injection. While screening potent VEGFR2 inhibitors at the enzyme and cellular levels, ensuring the safety of the compounds was our primary strategy for screening optimal compounds. Finally, compound 16 was identified, exhibiting enhanced inhibition of VEGFR2 enzyme and proliferation of BaF3-TEL-VEGFR2 cells compared to Vorolanib. Compound 16 had a weak inhibitory effect on human Ether-a-go-go-related gene (hERG) channel currents, showing a cardiac safety profile similar to Vorolanib. Compound 16 showed no significant toxicity to human liver cell LX-2, indicating a liver safety profile similar to Vorolanib. The water solubility of compound 16 was found to be higher than that of Vorolanib when tested at pH = 7.4. In addition, compound 16 was found to inhibit VEGFR2 phosphorylation in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner by WB assay. Furthermore, the in vitro preliminary evaluation of the drug-like properties of compound 16 showed remarkable plasma stability and moderate liver microsomal stability. Based on in vivo pharmacokinetic studies in ICR mice, compound 16 exhibited acceptable oral bioavailability (F = 20.2 %). Overall, these findings provide evidence that compound 16 is a leading potential oral drug candidate for w-AMD.


Asunto(s)
Degeneración Macular , Ratones , Animales , Humanos , Ratones Endogámicos ICR , Células Endoteliales de la Vena Umbilical Humana , Degeneración Macular/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular
6.
Chin J Nat Med ; 22(1): 15-30, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38278556

RESUMEN

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.


Asunto(s)
Ácido Oleanólico , Triterpenos , Relación Estructura-Actividad , Antiinflamatorios/farmacología , Antibacterianos/farmacología
7.
Eur J Med Chem ; 265: 116071, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38157596

RESUMEN

In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC50 = 30.35 ± 2.07 nM) and human butyrylcholinesterase (hBuChE, IC50 = 48.03 ± 6.41 nM) with minimal neurotoxicity. Further investigations have demonstrated that C7 exhibited a remarkable capacity to safeguard PC12 cells against H2O2-induced apoptosis and effectively suppressed the production of reactive oxygen species (ROS). Moreover, in an inflammation model of BV2 cells induced by lipopolysaccharide (LPS), C7 effectively attenuated the levels of pro-inflammatory cytokines. After 12 h of dialysis, C7 continued to exhibit an inhibitory effect on cholinesterase activity. An acute toxicity test in vivo demonstrated that C7 exhibited a superior safety profile and no hepatotoxicity compared to the parent nucleus tacrine. In the scopolamine-induced AD mouse model, C7 (20 mg/kg) significantly reduced cholinesterase activity in the brain of the mice. C7 was tested in a pharmacological AD mouse model induced by Aß1-42 and attenuated memory deficits at doses as low as 5 mg/kg. The pseudo-irreversible cholinesterase inhibitory properties and multifunctional therapeutic attributes of C7 render it a promising candidate for further investigation in the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer , Inhibidores de la Colinesterasa , Ratas , Ratones , Humanos , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/inducido químicamente , Butirilcolinesterasa/metabolismo , Tacrina/farmacología , Tacrina/uso terapéutico , Acetilcolinesterasa/metabolismo , Carbamatos/farmacología , Peróxido de Hidrógeno/farmacología , Péptidos beta-Amiloides , Barrera Hematoencefálica/metabolismo , Diseño de Fármacos , Relación Estructura-Actividad
8.
Light Sci Appl ; 12(1): 165, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37402713

RESUMEN

Chiral zeroth Landau levels are topologically protected bulk states. In particle physics and condensed matter physics, the chiral zeroth Landau level plays a significant role in breaking chiral symmetry and gives rise to the chiral anomaly. Previous experimental works on such chiral Landau levels are mainly based on three-dimensional Weyl degeneracies coupled with axial magnetic fields. Their realizations using two-dimensional Dirac point systems, being more promising for future applications, were never experimentally realized before. Here we propose an experimental scheme for realizing chiral Landau levels in a two-dimensional photonic system. By introducing an inhomogeneous effective mass through breaking local parity-inversion symmetries, a synthetic in-plane magnetic field is generated and coupled with the Dirac quasi-particles. Consequently, the zeroth-order chiral Landau levels can be induced, and the one-way propagation characteristics are experimentally observed. In addition, the robust transport of the chiral zeroth mode against defects in the system is also experimentally tested. Our system provides a new pathway for the realization of chiral Landau levels in two-dimensional Dirac cone systems, and may potentially be applied in device designs utilizing the chiral response and transport robustness.

9.
Phys Rev Lett ; 130(24): 243801, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37390435

RESUMEN

Owing to the chirality of Weyl nodes characterized by the first Chern number, a Weyl system supports one-way chiral zero modes under a magnetic field, which underlies the celebrated chiral anomaly. As a generalization of Weyl nodes from three-dimensional to five-dimensional physical systems, Yang monopoles are topological singularities carrying nonzero second-order Chern numbers c_{2}=±1. Here, we couple a Yang monopole with an external gauge field using an inhomogeneous Yang monopole metamaterial and experimentally demonstrate the existence of a gapless chiral zero mode, where the judiciously designed metallic helical structures and the corresponding effective antisymmetric bianisotropic terms provide the means for controlling gauge fields in a synthetic five-dimensional space. This zeroth mode is found to originate from the coupling between the second Chern singularity and a generalized 4-form gauge field-the wedge product of the magnetic field with itself. This generalization reveals intrinsic connections between physical systems of different dimensions, while a higher-dimensional system exhibits much richer supersymmetric structures in Landau level degeneracy due to the internal degrees of freedom. Our study offers the possibility of controlling electromagnetic waves by leveraging the concept of higher-order and higher-dimensional topological phenomena.

10.
Phys Rev Lett ; 130(20): 203802, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37267572

RESUMEN

In periodic systems, band degeneracies are typically protected and classified by spatial symmetries. However, in photonic systems, the Γ point at zero frequency is an intrinsic degeneracy due to the polarization degree of freedom of electromagnetic waves. For chiral photonic crystals, such an intrinsic degeneracy carries ±2 chiral topological charge while having linear band dispersions, different from the general perception of charge-2 nodes being associated with quadratic dispersions. Here, we show that these topological characters originate from the spin-1 Weyl point at zero frequency node of triple degeneracy, due to the existence of an electrostatic flat band. Such a topological charge at zero frequency is usually buried in bulk band projections and has never been experimentally observed. To address this challenge, we introduce space-group screw symmetries in the design of chiral photonic crystal, which makes the Brillouin zone boundary an oppositely charged nodal surface enclosing the Γ point. As a result, the emergent Fermi arcs are forced to connect the projections of these topological singularities, enabling their experimental observation. The number of Fermi arcs then directly reveals the embedded topological charge at zero frequency.

11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(2): 152-157, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-36916375

RESUMEN

OBJECTIVE: To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers. METHODS: Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis. RESULTS: Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/ß-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). CONCLUSIONS: DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.


Asunto(s)
Síndrome de Dificultad Respiratoria , Sepsis , Ratas , Masculino , Animales , Interleucina-10 , Factor A de Crecimiento Endotelial Vascular , Interleucina-6 , Proteína D Asociada a Surfactante Pulmonar , Factor de Necrosis Tumoral alfa
12.
J Enzyme Inhib Med Chem ; 38(1): 2192439, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36950955

RESUMEN

A series of OA-tacrine hybrids with the alkylamine linker was designed, synthesized, and evaluated as effective cholinesterase inhibitors for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some hybrids possessed significant inhibitory activities against acetylcholinesterase (AChE). Among them, compounds B4 (hAChE, IC50 = 14.37 ± 1.89 nM; SI > 695.89) and D4 (hAChE, IC50 = 0.18 ± 0.01 nM; SI = 3374.44) showed excellent inhibitory activities and selectivity for AChE as well as low nerve cell toxicity. Furthermore, compounds B4 and D4 exhibited lower hepatotoxicity than tacrine in cell viability, apoptosis, and intracellular ROS production for HepG2 cells. These properties of compounds B4 and D4 suggest that they deserve further investigation as promising agents for the prospective treatment of AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Tacrina/farmacología , Inhibidores de la Colinesterasa/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Acetilcolinesterasa/metabolismo , Relación Estructura-Actividad
13.
Bioorg Chem ; 134: 106441, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36854233

RESUMEN

A novel series of N-methyl-propargylamine derivates were designed, synthesized, and evaluated as isoform-selective monoamine oxidases (MAO) inhibitors for the treatment of nervous system diseases. The in vitro studies showed some of the compounds exhibited considerable MAO-A selective inhibitory activity (IC50 of 14.86-17.16 nM), while some of the others exhibited great MAO-B selective inhibitory activity (IC50 of 4.37-17.00 nM). Further studies revealed that compounds A2 (IC50 against MAO-A: 17.16 ± 1.17 nM) and A5 (IC50 against MAO-B: 17.00 ± 1.10 nM) had significant abilities to protect PC12 cells from H2O2-induced apoptosis and reactive oxygen species (ROS) production. The parallel artificial membrane permeability assay showed A2 and A5 would be potent to cross the blood-brain barrier. The results indicated that A2 showed potential use in the therapy of MAO-A related diseases, such as depression and anxiety; while A5 exhibited promising ability in the treatment of MAO-B related diseases, such as Alzheimer's disease and Parkinson's disease.


Asunto(s)
Enfermedad de Alzheimer , Peróxido de Hidrógeno , Ratas , Animales , Relación Estructura-Actividad , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo
14.
AIDS ; 37(5): 723-731, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36625252

RESUMEN

OBJECTIVE: Sexually transmitted infections (STIs) increase mucosal HIV infection risk and have the potential to reduce preexposure prophylaxis efficacy. Clinical trials of a broadly neutralizing antibody (bNAb) provided proof-of-concept that passive immunization against HIV can be efficacious in people. We sought to evaluate preclinically the protective efficacy of passive bNAb immunization against simian-human immunodeficiency virus (SHIV) infection in the context of concurrent vaginal STIs. DESIGN: Using a macaque model of combined ulcerative and nonulcerative vaginal STIs caused by Treponema pallidum , Chlamydia trachomatis , and Trichomonas vaginalis , we determined the protection that passively administered bNAb 10-1074 conferred against repeated vaginal SHIV challenges and compared correlates of protection to contemporaneous and historical controls without STIs. METHODS: Plasma viremia was monitored via RT-qPCR assay. Concentrations of 10-1074 were determined longitudinally in plasma samples via TZM-bl pseudovirus neutralization assay. RESULTS: Among macaques with vaginal STIs, a single subcutaneous injection of 10-1074 durably protected against vaginal SHIV acquisition, as compared with untreated controls. Interestingly, the median plasma concentration of 10-1074 at the time of SHIV breakthrough among macaques with STIs was significantly higher (10-fold) than that previously observed among 10-1074-treated macaques in the absence of STIs. CONCLUSION: Passive immunization with 10-1074 conferred significant protection against repeated vaginal SHIV challenges among macaques harboring vaginal STIs. However, our findings suggest that higher bNAb concentrations may be required for prophylaxis when STIs are present. Our findings potentially impact dose selection for the clinical development of bNAbs and highlight the importance of additional preclinical efficacy testing in STI models.


Asunto(s)
Infecciones por VIH , VIH-1 , Enfermedades de Transmisión Sexual , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Femenino , Humanos , Anticuerpos ampliamente neutralizantes , Macaca , Enfermedades de Transmisión Sexual/prevención & control , Anticuerpos Anti-VIH , Anticuerpos Neutralizantes
15.
Wei Sheng Yan Jiu ; 51(5): 746-752, 2022 Sep.
Artículo en Chino | MEDLINE | ID: mdl-36222036

RESUMEN

OBJECTIVE: To investigate the relationship between obesity indicators and dyslipidemia and hypertension in the Yao population of Guangxi. METHODS: In 2015, we examined the body composition data of 784 Yao residents aged 18 years or older in Guangxi using a multi-stage whole-group random sampling method, analyzed the association between 10 indicators responding to the degree of obesity and dyslipidemia and hypertension, and analyzed the predictive value of each obesity indicator for dyslipidemia and hypertension by receiver operating characteristic(ROC) curves. RESULTS: There were 58.80% of Yao adults with dyslipidemia, with no difference between men and women(χ~2=0.24, P>0.05); 15.94% of Yao adults had hypertension, with a higher prevalence in men than in women(χ~2=4.76, P<0.05). ROC curves plotted with dyslipidemia as the dependent variable showed that the best predictor of risk of dyslipidemia prevalence in the Yao adult population was waist-to-hip ratio(WHR)(AUC=0.62, 95% CI 0.56-0.68) with a cut point of 0.86 in men and waist circumference(AUC=0.64, 95% CI 0.59-0.69) with a cut point of 75.50 cm in women. The ROC curves were plotted with hypertension as the dependent variable, and the result showed that the best predictor of risk of hypertension in the Yao adult population was: visceral fat content(AUC=0.62, 95% CI 0.56-0.68) with a cut point of 0.65 kg in men and WHR(AUC=0.67, 95% CI 0.62-0.72) with a cut point of 0.82 in women. CONCLUSION: Compared with indicators reflecting general obesity such as body mass index and percentage of body fat, indicators reflecting abdominal obesity such as waist circumference, WHR and visceral fat content are more closely related to two metabolic diseases such as dyslipidemia and hypertension in the Yao population.


Asunto(s)
Dislipidemias , Hipertensión , Adulto , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Dislipidemias/epidemiología , Etnicidad , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Obesidad/epidemiología , Curva ROC , Factores de Riesgo , Circunferencia de la Cintura , Relación Cintura-Cadera
16.
Bioorg Chem ; 129: 106213, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36308854

RESUMEN

Inosine 5'-monophosphate dehydrogenase (IMPDH; EC1.1.1.205) is the rate-limiting enzyme of GMP biosynthesis. The inhibition of IMPDH limits the growth and survival of tumors. Based on the systematic summary of clinical IMPDH inhibitors, 38 acrylamide derivatives with differently substituted indoles at the 3-position as the core scaffold were designed and synthesized. In addition, the actions of these compounds at the enzyme and cellular levels were evaluated. An MTT assay with different kinds of cells was used to assess the cytotoxic activities of compounds 14e and 14n, which displayed potent hIMPDH2 inhibitory activities (IC50 = 4.207 and 2.948 µM, respectively). Biological evaluation indicated that target compounds 14e and 14n displayed the most significant effects on SW480 human colon cancer cells (IC50 = 15.34 ± 0.06 and 15.31 ± 0.09 µM, respectively), and it was determined that these compounds are effective and valuable IMPDH inhibitors for cancer intervention.


Asunto(s)
Acrilamida , Antineoplásicos , Humanos , Acrilamida/farmacología , IMP Deshidrogenasa , Inhibidores Enzimáticos/farmacología , Antineoplásicos/farmacología , Indoles/farmacología
17.
Theor Appl Genet ; 135(9): 3277-3291, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35916916

RESUMEN

KEY MESSAGE: Six wheat-Thinopyrum ponticum disomic addition lines derived from partial amphiploid Xiaoyan 7430 were identified using in situ hybridization and SNP microarray, the homoeologous group and stripe rust resistance of each alien chromosome were determined, and Th. ponticum chromosome-specific markers were developed. Xiaoyan 7430 is a significant partial amphiploid, which is used to set up a bridge for transferring valuable genes from Thinopyrum ponticum (Podp.) Barkworth & D.R. Dewey into common wheat. To accelerate the application of these useful genes in enriching the genetic variability of cultivated wheat by chromosome engineering, a complete set of derived addition lines has been created from Xiaoyan 7430. The chromosome composition of each line was characterized by the combination of genomic in situ hybridization and multicolor fluorescence in situ hybridization (mc-FISH), and the homoeology of each alien chromosome was determined by wheat SNP microarray analysis. Addition line WTA55 with alien group-6 chromosome was evaluated resistant to stripe rust isolates at both the seedling and grain-filling stages (Zadoks scale at z.11 and z.73). Diagnostic marker analysis proved that it could carry a novel stripe rust resistance gene derived from Th. ponticum. Furthermore, a FISH probe and 45 molecular markers specific for alien chromosomes were developed based on specific-locus amplified fragment sequencing (SLAF-seq). Of which 27 markers were separately located on single alien chromosome, and some of them could be used to identify the derived translocation lines. This set of addition lines as well as the molecular markers and the FISH probe will promote the introgression of abundant variation from Th. ponticum into wheat in wheat improvement programs.


Asunto(s)
Basidiomycota , Triticum , Cromosomas de las Plantas/genética , Resistencia a la Enfermedad/genética , Marcadores Genéticos , Hibridación Fluorescente in Situ , Enfermedades de las Plantas/genética , Poaceae/genética , Triticum/genética
18.
BMC Musculoskelet Disord ; 23(1): 594, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35725467

RESUMEN

BACKGROUND: Percutaneous cement discoplasty (PCD) is a minimally invasive treatment for degenerative lumbar spine disease, but the relationship between decompression effect on the nerve root and different doses of bone cement is uncertain. PURPOSE: To investigate the indirect decompression effect of cement with different doses on nerve roots and the biomechanical changes on the spine during PCD using finite element analysis (FEA). METHODS: FEA was adapted to analyze the mechanical changes in the lumbar vertebrae before and after the application of PCD.CT scan images of adult males were utilized to establish a finite element model of the lumbar vertebral body using mimics and Pro/E software. The images were divided into four models: the normal model (normal, model N), the disc degeneration model (high, model H), the intervertebral disc injected with 3 mL of bone cement (model H1), and the intervertebral disc injected with 5 mL of bone cement (model H2). All models were analyzed using the ABAQUS6.14.2 software. The normal physiological movements were simulated, and the mechanical changes in the lumbar vertebrae were observed prior to and after the cement filling application. RESULTS: The stress of the nerve root in model H was the largest. The nerve root stress in the model H2 was the smallest during flexion, extension, left bending, right bending, left rotation, and right rotation at 90%, 44%, 25%, 56%, 56%, and 51% of the normal benchmark, respectively. After the injection of bone cement, the nerve root stress is reduced. The greater the amount of cement, the lesser the nerve root stress. The motion was reduced in models H, H1, and H2, and there were differences between models H1 and H2. Cartilage endplate stress was less in model H2 than in model H1. CONCLUSIONS: The nerve root stress increased after degeneration and decreased after intervertebral height recovery through cement injection, resulting in a significant indirect decompression effect.The stress of the nerve root decreased with the increase in the amount of cement injection.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Adulto , Fenómenos Biomecánicos , Cementos para Huesos/uso terapéutico , Análisis de Elementos Finitos , Humanos , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Masculino , Rango del Movimiento Articular
19.
Org Lett ; 24(23): 4234-4239, 2022 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-35658480

RESUMEN

Described herein is an efficient strategy for assembling a new library of functionalized polycyclic purinium salts with a wide range of anions through RhIII-catalyzed C-H activation/annulation of 6-arylpurine nucleosides with alkynes under mild reaction conditions. The resulting products displayed tunable photoluminescence covering most of the visible spectrum. Mechanistic insights delineated the rhodium catalyst's mode of action. A purinoisoquinolinium-coordinated rhodium(I) sandwich complex was well characterized and identified as the key intermediate.


Asunto(s)
Rodio , Alquinos , Catálisis , Nucleósidos , Sales (Química)
20.
BMC Endocr Disord ; 22(1): 38, 2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35148746

RESUMEN

BACKGROUND: Components of the RAAS may influence bone metabolism. Different roles of the RAAS are found in patients with primary aldosteronism (PA), Gitelman syndrome (GS) and Bartter syndrome (BS). We collected inpatient medical records including 20 patients with Gitelman syndrome (GS group), 17 patients with Bartter syndrome (BS group) and 20 age-matched patients with primary aldosteronism (PA group). We found the following results. (1) PA patients had significantly higher serum magnesium, potassium, plasma aldosterone, serum parathyroid hormone, urinary calcium and BMI (p<0.05) while significantly lower serum calcium and phosphorus (P < 0.05) than GS and BS patients. (2) Total hip and femoral neck bone mineral density (BMD) in PA patients were significantly lower than those in GS and BS patients (P<0.05). (3) GS patients had lower serum magnesium and urinary calcium than BS patients (P < 0.05). (4) Compared with BS patients, the vertebral BMD in GS patients were significantly higher (P < 0.05). So we believe higher aldosterone and PTH levels may be the reason that PA patients have lower hip BMD. Lower urinary calcium and inactivation of the NCC gene (Na-Cl cotransporter) in GS patients may have protective effects on vertebral bone mineral density. CONCLUSIONS: With persistence disordered RAAS, PA patients have lower BMD, especially hip BMD as compared with GS and BS patients. We presumed the lower renin and higher aldosterone level may be the reason. With the same level of renin and aldosterone, BS patients have lower vertebrate BMD than GS patients. Decreased urinary calcium excretion may be the reason.


Asunto(s)
Síndrome de Bartter/metabolismo , Huesos/metabolismo , Síndrome de Gitelman/metabolismo , Hiperaldosteronismo/metabolismo , Sistema Renina-Angiotensina/fisiología , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Densidad Ósea , Femenino , Humanos , Masculino , Persona de Mediana Edad
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