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1.
J Neurophysiol ; 131(2): 176-186, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38117913

RESUMEN

Insomnia, recognized as a prevalent sleep disorder, has garnered extensive attention within the realm of public health. Recent studies indicate a close interaction between the immune system and sleep; however, the specific mechanism remains not yet fully understood. Based on the publicly available Genome-Wide Association Study (GWAS) data, we used two-sample Mendelian randomization (MR) analyses to investigate the associations between 731 immune cell traits and insomnia risk. Five MR analysis methods and a comprehensive sensitivity analysis were used to evaluate the reliability of the results. In this study, we identified that 14 immune characteristics among four immune profiles [median fluorescence intensity (MFI), relative cell count (RC), absolute cell count (AC), and morphological parameters (MP)] demonstrated a significant causal association with insomnia. Specifically, eight immune cell characteristics were associated with an increased risk of insomnia, including CD11c+ monocyte% (P < 0.001), CD11c+ HLA DR++ monocyte% (P = 0.004), CD86+ plasmoid dendritic cell (DC) AC (P < 0.001), CD33br HLA DR+ CD14dim AC (P < 0.001), CD8dim AC (P = 0.002), CCR2 on CD14+ CD16- monocyte (P < 0.001), CD39 on monocyte (P < 0.001), and SSC-A on myeloid DC (P < 0.001). Six immune cell characteristics demonstrated protective effects against insomnia, including PB/PC %B cell (P < 0.001), CM CD4+% CD4+ (P < 0.001), T-cell AC (P < 0.001), BAFF-R on IgD- CD38br (P < 0.001), CD16-CD56 on HLA DR+ NK cells (P < 0.001), and CD14 on CD33br HLA DR+ CD14dim (P < 0.001). Our study established the correlation between immune cell characteristics and insomnia, offering a novel theoretical foundation for the concept of sleep-immune cross talk.NEW & NOTEWORTHY This study investigated the association between 731 immune cell characteristics and insomnia using Mendelian randomization, revealing that 14 immune cell characteristics across four groups of immune traits (MFI, RC, AC, and MP) have a significant and causal association with insomnia risk. Our results contribute to the understanding of the sleep-immune cross talk doctrine and offer a new theoretical basis for immune modulation in treating insomnia.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Reproducibilidad de los Resultados , Antígenos HLA-DR/análisis
2.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39000259

RESUMEN

Molecular breeding accelerates animal breeding and improves efficiency by utilizing genetic mutations. Structural variations (SVs), a significant source of genetic mutations, have a greater impact on phenotypic variation than SNPs. Understanding SV functional mechanisms and obtaining precise information are crucial for molecular breeding. In this study, association analysis revealed significant correlations between 198-bp SVs in the GSTA2 promoter region and abdominal fat weight, intramuscular fat content, and subcutaneous fat thickness in chickens. High expression of GSTA2 in adipose tissue was positively correlated with the abdominal fat percentage, and different genotypes of GSTA2 exhibited varied expression patterns in the liver. The 198-bp SVs regulate GSTA2 expression by binding to different transcription factors. Overexpression of GSTA2 promoted preadipocyte proliferation and differentiation, while interference had the opposite effect. Mechanistically, the 198-bp fragment contains binding sites for transcription factors such as C/EBPα that regulate GSTA2 expression and fat synthesis. These SVs are significantly associated with chicken fat traits, positively influencing preadipocyte development by regulating cell proliferation and differentiation. Our work provides compelling evidence for the use of 198-bp SVs in the GSTA2 promoter region as molecular markers for poultry breeding and offers new insights into the pivotal role of the GSTA2 gene in fat generation.


Asunto(s)
Adipogénesis , Pollos , Glutatión Transferasa , Regiones Promotoras Genéticas , Animales , Adipogénesis/genética , Pollos/genética , Pollos/crecimiento & desarrollo , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/genética , Proliferación Celular/genética , Regulación de la Expresión Génica , Tejido Adiposo/metabolismo
3.
Anal Chem ; 95(45): 16505-16513, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37902600

RESUMEN

De novo sequencing of oligonucleotides remains challenging, especially for oligonucleotides with post-transcriptional or synthetic modifications. Mass spectrometry (MS) sequencing can reliably detect and locate all of the modification sites in oligonucleotides via m/z variance. However, current MS-based sequencing methods exhibit complex spectra and low ion abundance and usually require coupled instrumentation. Herein, we demonstrate a method of oligonucleotide sequencing using TiO2/ZnAl-layered double oxide (LDO)-assisted laser desorption/ionization (LDI)-MS based on radical-induced dissociation (RID). ·CH2OH radicals can be produced on the surface of a TiO2/ZnAl-LDO matrix via ultraviolet light, inducing an attack on the active site of the oligonucleotide phosphate skeleton to create typical "a-, a-B-, c·-, d-, w-, and y"-type fragments. Compared with the spectra obtained via collision-based methods, such as collision-induced dissociation and higher-energy collisional dissociation, the LDI-MS spectra based on RID exhibit single-charged signals, fewer types of fragments, and a lower proportion of unknown noise peaks. We demonstrate full sequence coverage for a 6-mer 2'-O-methyl-modified oligonucleotide and a 21-mer small interfering RNA and show that RID can sequence oligonucleotides with modifications. Importantly, the mechanism responsible for the RID of the oligonucleotide phosphate skeleton was investigated through offline experiments, demonstrating consistent results with density functional theory calculations.


Asunto(s)
Oligonucleótidos , Óxidos , Oligonucleótidos/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Fosfatos
4.
J Org Chem ; 88(4): 2550-2556, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-35043626

RESUMEN

A simple, green halide-catalyzed protocol for disulfuration of indole derivatives with N-dithiophthalimides has been developed. This C-H disulfide reaction proceeded smoothly at room temperature with economical LiBr as catalyst, providing an effective method for the synthesis of novel unsymmetrical disulfides. A series of 3-dithioindole derivatives were obtained in high yields with good functional group tolerance; moreover, the wide scope of Harpp reagents (aryl, benzyl, primary, secondary, tertiary) confirmed the practicability of this approach.

5.
Anal Chem ; 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36562720

RESUMEN

The atmospheric oxidation of chemicals has produced many new unpredicted pollutants. A microwave plasma torch-based ion/molecular reactor (MPTIR) interfacing an online mass spectrometer has been developed for creating and monitoring rapid oxidation reactions. Oxygen in the air is activated by the plasma into highly reactive oxygen radicals, thereby achieving oxidation of thioethers, alcohols, and various environmental pollutants on a millisecond scale without the addition of external oxidants or catalysts (6 orders of magnitude faster than bulk). The direct and real-time oxidation products of polycyclic aromatic hydrocarbons and p-phenylenediamines from the MPTIR match those of the long-term multistep environmental oxidative process. Meanwhile, two unreported environmental compounds were identified with an MPTIR and measured in the actual water samples, which demonstrates the considerable significance of the proposed device for both predicting the environmental pollutants (non-target screening) and studying the mechanism of atmospheric oxidative processes.

6.
Vet Res ; 53(1): 1, 2022 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-34998433

RESUMEN

To understand the differences in immune responses between early feathering (EF) and late feathering (LF) chickens after infection with avian leukosis virus, subgroup J (ALV-J), we monitored the levels of prolactin, growth hormone and the immunoglobulins IgG and IgM in the serum of LF and EF chickens for 8 weeks. Moreover, we analysed the expression of immune-related genes in the spleen and the expression of PRLR, SPEF2 and dPRLR in the immune organs and DF-1 cells by qRT-PCR. The results showed that ALV-J infection affected the expression of prolactin, growth hormone, IgG and IgM in the serum. Regardless of whether LF and EF chickens were infected with ALV-J, the serum levels of the two hormones and two immunoglobulins in EF chickens were higher than those in LF chickens (P < 0.05). However, the expression of immune-related genes in the spleen of positive LF chickens was higher than that in the spleen of positive EF chickens. In the four immune organs, PRLR and SPEF2 expression was also higher in LF chickens than in EF chickens. Furthermore, the dPRLR expression of positive LF chickens was higher than that of negative LF chickens. After infection with ALV-J, the expression of PRLR in DF-1 cells significantly increased. In addition, overexpression of PRLR or dPRLR in DF-1 cells promoted replication of ALV-J. These results suggested that the susceptibility of LF chickens to ALV-J might be induced by dPRLR.


Asunto(s)
Virus de la Leucosis Aviar , Leucosis Aviar , Enfermedades de las Aves de Corral , Receptores de Prolactina , Animales , Leucosis Aviar/inmunología , Virus de la Leucosis Aviar/inmunología , Pollos , Hormona del Crecimiento , Inmunidad , Inmunoglobulina G , Inmunoglobulina M , Prolactina , Receptores de Prolactina/inmunología
7.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36232654

RESUMEN

Adult skeletal muscle is primarily divided into fast and slow-type muscles, which have distinct capacities for regeneration, metabolism and contractibility. Satellite cells plays an important role in adult skeletal muscle. However, the underlying mechanisms of satellite cell myogenesis are poorly understood. We previously found that Sox6 was highly expressed in adult fast-type muscle. Therefore, we aimed to validate the satellite cell myogenesis from different muscle fiber types and investigate the regulation of Sox6 on satellite cell myogenesis. First, we isolated satellite cells from fast- and slow-type muscles individually. We found that satellite cells derived from different muscle fiber types generated myotubes similar to their origin types. Further, we observed that cells derived from fast muscles had a higher efficiency to proliferate but lower potential to self-renew compared to the cells derived from slow muscles. Then we demonstrated that Sox6 facilitated the development of satellite cells-derived myotubes toward their inherent muscle fiber types. We revealed that higher expression of Nfix during the differentiation of fast-type muscle-derived myogenic cells inhibited the transcription of slow-type isoforms (MyH7B, Tnnc1) by binding to Sox6. On the other hand, Sox6 activated Mef2C to promote the slow fiber formation in slow-type muscle-derived myogenic cells with Nfix low expression, showing a different effect of Sox6 on the regulation of satellite cell development. Our findings demonstrated that satellite cells, the myogenic progenitor cells, tend to develop towards the fiber type similar to where they originated. The expression of Sox6 and Nfix partially explain the developmental differences of myogenic cells derived from fast- and slow-type muscles.


Asunto(s)
Músculo Esquelético , Mioblastos , Diferenciación Celular , Células Cultivadas , Desarrollo de Músculos/genética , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Isoformas de Proteínas/metabolismo
8.
J Enzyme Inhib Med Chem ; 36(1): 593-604, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33557648

RESUMEN

Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Cumarinas/farmacología , Diseño de Fármacos , Tiocarbamatos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Cumarinas/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Tiocarbamatos/química , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo
9.
BMC Genet ; 21(1): 91, 2020 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-32847500

RESUMEN

BACKGROUND: G-protein subunit beta 1 like (GNB1L) encodes a G-protein beta-subunit-like polypeptide. Chicken GNB1L is upregulated in the breast muscle of high feed efficiency chickens, and its expression is 1.52-fold that in low feed efficiency chickens. However, no report has described the effects of GNB1L indels on the chicken carcass and growth traits. RESULTS: This study identified a 31-bp indel in the 5' untranslated region (UTR) of GNB1L and elucidated the effect of this gene mutation on the carcass and growth traits in chickens. The 31-bp indel showed a highly significant association with the body weight at 8 different stages and was significantly correlated with daily gains at 0 to 4 weeks and 4 to 8 weeks. Similarly, the mutation was significantly associated with small intestine length, breast width, breast depth and breast muscle weight. Moreover, DD and ID were superior genotypes for chicken growth and carcass traits. CONCLUSIONS: These results show that the 31-bp indel of GNB1L significantly affects chicken body weight and carcass traits and can serve as a candidate molecular marker for chicken genetics and breeding programs.


Asunto(s)
Regiones no Traducidas 5' , Pollos/genética , Mutación INDEL , Péptidos y Proteínas de Señalización Intracelular/genética , Animales , Peso Corporal/genética , Cruzamiento , Genotipo , Carne , Fenotipo
10.
Sensors (Basel) ; 19(22)2019 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-31744145

RESUMEN

In this study, a simple and green hydrothermal treatment was performed to prepare nitrogen-doped carbon dots (NCDs) from Averrhoa carambola (AC) fruit extract as a carbon precursor and L-arginine (Arg) as a nitrogen dopant. The AC-NCDs were characterized by UV light, fluorescence spectroscopy, transmission electron microscopy, FTIR spectroscopy, Raman spectroscopy, UV-vis spectroscopy, and zeta potential analyzer. The AC-NCDs were spherical and the average diameter was estimated to be 6.67 nm. The AC-NCDs exhibited the maximum emission intensity at 446 nm with 360 nm excitation wavelength. The fluorescence quenching behavior of AC-NCDs after interacting with methyl orange (MO) dye was studied. The interaction of AC-NCDs and MO was achieved within 3 min and the fluorescence quenching was maintained to a fixed value even after 30 min. The linearity was obtained in the range of 1 to 25 µM MO with a 0.30 µM detection limit. Furthermore, the pH values affected the quenching behavior of the AC-NCDs/MO system where the interaction mechanisms were driven by the electrostatic interaction, π-π interaction, inner filter effect, and energy transfer. The pH 5 maintained higher quenching efficiency while other pH values slightly decreased the quenching efficiency. Incoming applications, the AC-NCDs can be used in various important fields, especially for environmental protection.


Asunto(s)
Averrhoa/química , Compuestos Azo/aislamiento & purificación , Técnicas Biosensibles , Puntos Cuánticos/química , Compuestos Azo/química , Carbono/química , Colorantes Fluorescentes/química , Frutas/química , Límite de Detección , Microscopía Electrónica de Transmisión , Nitrógeno , Extractos Vegetales/química , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman
11.
J Tradit Chin Med ; 36(2): 205-10, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27400475

RESUMEN

OBJECTIVE: To evaluate the influence of the Tibetan medicine RuPeng15 powder (RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models. METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily (30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase (XOD) was assayed using a commercial test kit. RESULTS: RPP15 (0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats (P < 0.05). Furthermore, hyperuricemic rats treated with RPP15 (0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels (P < 0.05), accompanied by lower urine uric acid (P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly (P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15 (P < 0.05). CONCLUSION: RPP15 (0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Hiperuricemia/tratamiento farmacológico , Ácido Úrico/sangre , Animales , Humanos , Hiperuricemia/sangre , Hiperuricemia/metabolismo , Hígado/enzimología , Masculino , Medicina Tradicional Tibetana , Ratas , Xantina Oxidasa/metabolismo
12.
Front Med (Lausanne) ; 11: 1355262, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633316

RESUMEN

Background: As population aging and unhealthy living habits may exacerbate the prevalence and burden of low back pain (LBP), effective treatment and improvement of patient quality of life are particularly critical. Silver needle therapy (SNT), having evolved from traditional acupuncture, involves placing silver needles into muscles, tendons, and fascia for treatment. However, it still lacks robust clinical evidence to substantiate its effectiveness. Therefore, it is necessary to conduct more emphasis on meta-analysis to evaluate the clinical efficacy of SNT for treating LBP. Methods: We will search PubMed, Medline, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Databases up until December 2023 to identify randomized controlled trials of SNT treatment in adult patients with LBP. The primary outcome will be the intensity of pain after pain management. Secondary outcomes will include the Oswestry Disability Index, Japanese Orthopedic Association Back Pain Evaluation Questionnaire, requirement for analgesic drugs, and treatment-related adverse reactions. Two investigators conducted the literature search, selected studies that might meet the inclusion criteria based on the title and abstract, and extracted data from the eligible literature independently and will independently assess the risk of bias using the Revised Cochrane Risk-of-Bias (RoB2) tool. Multivariate analyses (including subgroup analysis, trial sequential analysis (TSA), sensitivity analysis, etc.) will be conducted to improve the quality of evidence. Clinical trial registration: Registration: PROSPERO Registration Number: CRD42023466207, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023466207.

13.
Sci Rep ; 14(1): 14028, 2024 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890319

RESUMEN

Blood group is a potential genetic element in coronary artery disease. Nevertheless, the relationship between different ABO blood groups and myocardial injury after non-cardiac surgery (MINS) is poorly understood. This study verified whether ABO blood group is a potential MINS influencing factor. This retrospective cohort study included 1201 patients who underwent elective non-cardiac surgery and a mandatory troponin test on postoperative days 1 and 2 from 2019 to 2020 at a university-affiliated tertiary hospital. The primary outcome was associations between ABO blood groups and MINS, assessed using univariate and multivariate logistic-regression analyses. Path analysis was used to investigate direct and indirect effects between blood group and MINS. MINS incidence (102/1201, 8.5%) was higher in blood-type B patients than in non-B patients [blood-type B: 44/400 (11.0%) vs. non-B: 58/801 (7.2%); adjusted odds ratio = 1.57 (1.03-2.38); p = 0.036]. In the confounding factor model, preoperative hypertension and coronary artery disease medical history were associated with MINS risk [adjusted odds ratio: 2.00 (1.30-3.06), p = 0.002; 2.81 (1.71-4.61), p < 0.001, respectively]. Path analysis did not uncover any mediating role for hypertension, diabetes, or coronary artery disease between blood type and MINS. Therefore, blood-type B is associated with higher MINS risk; potential mediators of this association need to be investigated.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Sistema del Grupo Sanguíneo ABO/genética , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Procedimientos Quirúrgicos Electivos/efectos adversos
14.
Front Aging Neurosci ; 16: 1340110, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455666

RESUMEN

Background: Immunity and neuroinflammation play crucial roles in the pathogenesis of Parkinson's disease (PD). Nonetheless, prior investigations into the correlation between immune inflammation and PD have produced varying results. Identifying specific immune cell phenotypes that are truly associated with PD is challenging, and the causal relationship between immune cells and PD remains elusive. Methods: This study conducted a comprehensive two-sample Mendelian randomization (MR) analysis, employing five distinct analytical approaches, to clarify the causal connection between immune cell characteristics and the risk of PD. Utilizing GWAS data, we investigated the causal relationship between 731 immune cell traits and PD. These immune cell phenotypes encompass absolute cell (AC) counts, median fluorescence intensity (MFI), and relative cell (RC) counts for B cells, cDCs, mature stage T cells, monocytes, myeloid cells, TBNK (T cells, B cells, and natural killer cells), and Tregs, as well as the logistic parameter (MP) for cDCs and TBNK. Results: The inverse variance weighted (IVW) analysis indicated that Myeloid DCs (p = 0.004), HVEM expression on CD45RA- CD4+ T cells (p = 0.007), CD62L- CD86+ Myeloid DCs (p = 0.015), and HLA DR expression on monocytes (p = 0.019) were associated with a reduced risk of PD. CD14+ CD16+ monocytes (p = 0.005), HLA DR+ NK cells within CD3- lymphocytes (p = 0.023), and CD28 expression on activated & secreting Tregs (p = 0.032) were associated with an increased risk of PD. Conclusion: This study establishes a causal link between immune cell phenotype and the pathogenesis of PD, identifying several specific immune cell characteristics associated with PD. This could inspire researchers to delve into the pathogenesis of PD at the cellular subtype level, and aid in the identification of potential pharmacological protein targets for PD.

15.
Front Aging Neurosci ; 16: 1358996, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38425786

RESUMEN

Background: The epidemiological association between frailty and insomnia is well established, yet the presence of a common genetic etiology is still uncertain. Further exploration is needed to ascertain the causal relationship between frailty and insomnia. Methods: Utilizing data obtained from genome-wide association studies (GWAS) summaries, we utilized the linkage disequilibrium score regression (LDSC) to determine the genetic correlation existing between frailty and insomnia. The determination of causality was achieved through the application of two-sample Mendelian randomization. We investigated the enrichment of single nucleotide polymorphism (SNP) at various tissue types utilizing stratified LD score regression (S-LDSC) and multimarker analysis of genome annotation (MAGMA). Common risk SNPs were identified using Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC). We further investigated the expression profiles of risk genes in tissues using Summary-data-based Mendelian randomization(SMR) based on pooled data, to explore potential functional genes. Results: Our findings indicated a significant genetic correlation between frailty and insomnia, highlighting SNPs sharing risk (rs34290943, rs10865954), with a pronounced correlation in the localized genomic region 3p21.31. Partitioned genetic analysis revealed 24 functional elements significantly associated with both frailty and insomnia. Furthermore, mendelian randomization revealed a causal connection between frailty and insomnia. The genetic correlation between frailty and insomnia showed enrichment in 11 brain regions (S-LDSC) and 9 brain regions (MAGMA), where four functional genes (RMB6, MST1R, RF123, and FAM212A) were identified. Conclusion: This study suggests the existence of a genetic correlation and common risk genes between frailty and insomnia, contributing to a deeper comprehension of their pathogenesis and assists in identifying potential therapeutic targets.

16.
Front Genet ; 15: 1404456, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071775

RESUMEN

Background: Although genome-wide association studies (GWAS) have identified 14 loci associated with frailty index (FI) susceptibility, the underlying causative genes and biological mechanisms remain elusive. Methods: A cross-tissue transcriptome-wide association study (TWAS) was conducted utilizing the Unified Test for Molecular Markers (UTMOST), which integrates GWAS summary statistics from 164,610 individuals of European ancestry and 10,616 Swedish participants, alongside gene expression matrices from the Genotype-Tissue Expression (GTEx) Project. Validation of the significant genes was performed through three distinct methods: FUSION, FOCUS, and Multiple Marker Analysis of Genome-wide Annotation (MAGMA). Exploration of tissue and functional enrichment for FI-associated SNPs was conducted using MAGMA. Conditional and joint analyses, along with fine mapping, were employed to enhance our understanding of FI's genetic architecture. Mendelian randomization was employed to ascertain causal relationships between significant genes and FI, and co-localization analysis was utilized to investigate shared SNPs between significant genes and FI. Results: In this study, two novel susceptibility genes associated with the risk of FI were identified through the application of four TWAS methods. Mendelian randomization demonstrated that HTT may elevate the risk of developing frailty, whereas LRPPRC could offer protection against the onset of frailty. Additionally, co-localization analysis identified a shared SNP between LRPPRC and FI. Tissue enrichment analyses revealed that genomic regions linked to SNPs associated with frailty were predominantly enriched in various brain regions, including the frontal cortex, cerebral cortex, and cerebellar hemispheres. Conditional, combined analyses, and fine mapping collectively identified two genetic regions associated with frailty: 2p21 and 4q16.3. Functional enrichment analyses revealed that the pathways associated with frailty were primarily related to the MHC complex, PD-1 signaling, cognition, inflammatory response to antigenic stimuli, and the production of second messenger molecules. Conclusion: This investigation uncovers two newly identified genes with forecasted expression levels associated with the risk of FI, offering new perspectives on the genetic architecture underlying FI.

17.
J Am Soc Mass Spectrom ; 35(5): 951-959, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38597607

RESUMEN

C-H bond ortho-substitution reaction has always been a significant and challenging topic in organic chemistry. We proposed a synthesis method based on microwave plasma torches. High-resolution mass spectrometry was used to monitor rapid reaction products. 2-Alkylbenzimidazole can be formed through the reaction of phenylnitrenium ion and nitriles on a millisecond scale. This reaction can achieve the one-step formation of benzimidazoles from benzene ring single-substituted compounds without the addition of external oxidants or catalysts. A similar C-H bond activation reaction can be accomplished with ketones. Meanwhile, the microwave plasma reactor was modified, and the resulting 2-methylbenzimidazole was successfully collected, indicating the device has good application potential in organic reactions such as C-H bond activation reaction.

18.
Sci Rep ; 13(1): 3687, 2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36878972

RESUMEN

This study explored the risk factors and established a prediction model for intraoperative hypothermia (IOH) in patients undergoing robotic surgery. We conducted a retrospective survey of patients undergoing elective robotic surgery at the China-Japan Union Hospital of Jilin University during June 2020-October 2021 using institutional medical records. Intraoperative core temperatures and potential influencing factors were collected, and regression analyses were used to assess the risk factors for IOH and establish a prediction model for the incidence of IOH. Overall, 833 patients who underwent robotic surgery were included in the final analysis; IOH was observed in 344 patients (incidence, 0.41; 95% confidence interval [CI] 0.38-0.45). A higher body mass index (BMI) and baseline core temperature were protective factors for IOH. A final prediction model for IOH was developed based on the determining factors with an area under the receiver operating characteristic curve of 0.85 under fivefold cross validation (95% CI 0.83-0.88). Accordingly, a lower BMI and baseline core temperature, thoracic surgeries, morning surgeries, and surgeries with longer durations were risk factors for IOH during robotic surgeries. Our prediction model has an excellent discrimination ability for predicting IOH in robotic surgeries.


Asunto(s)
Hipotermia , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Hipotermia/epidemiología , Hipotermia/etiología , Estudios Retrospectivos , Factores de Riesgo
19.
BMJ Open ; 13(11): e071328, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37977865

RESUMEN

OBJECTIVE: Evaluate the feasibility of a trial of perioperative hypotension and serious complications. DESIGN: A patient and assessor-blinded randomised feasibility trial. SETTING: We included patients in a tertiary university hospital. PARTICIPANTS: We enrolled 80 adults scheduled for major non-cardiac surgery. INTERVENTIONS: In patients randomised to tight blood pressure control, intraoperative mean arterial pressure (MAP) was targeted to ≥85 mm Hg maintained with norepinephrine infusion, and restarting chronic antihypertensive medications was delayed until the third postoperative day. In the reference group, intraoperative blood pressure was managed per routine and antihypertensive medications were restarted immediately after surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: Our first co-primary outcome was the fraction of time when intraoperative MAP was >85 mm Hg, intraoperative area (time integral) of MAP >85 mm Hg and MAP <65 mm Hg. The second co-primary outcome was time until antihypertensive medications were restarted after surgery. Secondary outcomes were time-weighted average intraoperative MAP, cumulative minimum MAP for 10 min, average postoperative systolic blood pressure (SBP) and mean of the lowest three postoperative SBPs. RESULTS: Forty patients in each group were analysed. The median for intraoperative area of MAP >85 mm Hg was 1303 (772-2419) mm Hg*min in routine blood pressure (BP) cases and 2425 (1926-3545) mm Hg*min in tight BP control. The area for intraoperative MAP <65 mm Hg was 7 (0-40) mm Hg*min with routine BP management, and 0 (0-0) mm Hg*min with tight BP control. The fraction of time with MAP >85 mm Hg was 0.52 (0.25) and 0.87 (0.15). Antihypertensive medications were restarted 2 (1-3) days later in tight BP control cases. However, postoperative SBPs were similar. CONCLUSIONS: Tight BP management markedly increased intraoperative MAP and reduced the amount of hypotension. In contrast, delaying chronic antihypertensive medications had little effect on postoperative SBP. The full trial appears feasible and remains necessary but should not include postoperative antihypertensive management. TRIAL REGISTRATION: NCT04789733.


Asunto(s)
Hipertensión , Hipotensión , Adulto , Humanos , Presión Sanguínea , Antihipertensivos/uso terapéutico , Antihipertensivos/farmacología , Hipertensión/tratamiento farmacológico , Estudios de Factibilidad , Hipotensión/prevención & control , Hipotensión/tratamiento farmacológico
20.
BMJ Open ; 13(11): e069183, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37977873

RESUMEN

INTRODUCTION: Stellate ganglion block (SGB) is usually used in the department of algiatry. But preoperative SGB may reduce adverse cardiovascular events in high-risk patients, although evidence remains sparse. Therefore, we aim to determine whether a single-shot postoperative SGB can reduce the incidence of myocardial injury after non-cardiac surgery (MINS) and improve recovery in patients undergoing laparoscopic radical resection for colorectal cancer. METHODS AND ANALYSIS: This is an investigator-initiated, single-centre, randomised, two-arm clinical trial enrolling patients aged over 45 years and scheduled for elective laparoscopic radical colorectal surgery with at least one risk factor for MINS. A total of 950 eligible patients will be randomised into a routine or block groups. The primary outcome is the incidence of MINS. The secondary outcomes include the Visual Analogue Scale of pain during rest and movement, the incidence of delirium, quality of recovery (QOR) assessed by QOR-15, and sleep quality assessed by Richards Campbell Sleep Questionnaire. Tertiary outcomes include time to first flatus, gastrointestinal complications such as anastomotic leak or ileus, length of hospital stay, collapse incidence of severe cardiovascular and cerebrovascular complications of myocardial infarction, cardiac arrest, ischaemic or haemorrhagic stroke, and all-cause mortality within 30 days after the operation. ETHICS AND DISSEMINATION: The protocol was approved by Medical Ethics Committee of the China-Japan Union Hospital, Jilin University (Approval number: 2021081018) prior to recruitment. The study will be performed according to the guidelines of the Declaration of Helsinki. The findings of this study will be published and presented through various scientific forums. TRIAL REGISTRATION NUMBER: ChiCTR2200055319.


Asunto(s)
Neoplasias Colorrectales , Laparoscopía , Humanos , Anciano , Ganglio Estrellado , Pulmón , Laparoscopía/efectos adversos , Tiempo de Internación , Neoplasias Colorrectales/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto
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