Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 257
Filter
1.
Molecules ; 29(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998992

ABSTRACT

A new binuclear Gd(III) complex, [Gd2(L)6(Phen)2]·4H2O, was synthesized via the reaction of gadolinium(III) nitrate hexahydrate, 4-acetylphenoxyacetic acid (HL), NaOH, and 1,10-phenanthroline (Phen) in a solution of water-ethanol (v:v = 1:1). The Gd(III) complex was characterized using IR, UV-vis, TG-DSC, fluorescence, and single-crystal X-ray diffraction analyses. The results showed that the Gd(III) complex crystallizes in the triclinic system, space group P-1, and each Gd(III) ion was coordinated with two nitrogen atoms (N1, N2, or N1a, and N2a) from two Phen ligands and seven oxygen atoms (O1, O2, O7a, O9, O8, O8a, O10a, or O1a, O2a, O7, O8, O8a, O9a, and O10) from six L ligands, respectively, forming a nine-coordinated coordination mode. The Gd(III) complex molecules formed a one-dimensional chained and three-dimensional network structure via benzenering π-π stacking. The Hirschfeld surface analysis and the calculations of the electron density distributions of the frontier molecular orbitals of the Gd(III) complex were performed. The catalytic activities of the photocatalytic CO2 reduction and benzyl alcohol oxidation using the Gd(III) complex as a catalyst were performed. The results of the photocatalytic CO2 reduction showed that the yield and the selectivity of CO reached 41.5 µmol/g and more than 99% after four hours, respectively. The results of the benzyl alcohol oxidation showed that the yield of benzaldehyde was 45.7% at 120 °C with THF as the solvent under 0.5 MPa O2 within 2 h.

2.
Int J Surg ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913428

ABSTRACT

BACKGROUND: To some extent, robotic technique does offer certain benefits in rectal cancer surgery than laparoscopic one, while remains a topic of ongoing debate for rectal cancer patients who had undergone neoadjuvant chemoradiotherapy (NCRT). METHODS: Potential studies published until January 2024 were obtained from Web of Science, Cochrane Library, Embase and PubMed. Dichotomous and continuous variables were expressed as odds ratios (ORs) and weighted mean differences (WMDs) with 95% their confidence intervals (CIs), respectively. A random effects model was used if I2 statistic >50%, otherwise a fixed effects model. RESULTS: Eleven studies involving 1079 patients were analyzed. The robotic-assisted group had an 0.4 cm shorter distance from anal verge (95% CI: -0.680 to -0.114, P=0.006) and 1.94 times higher complete total mesorectal excision (TME) rate (OR=1.936, 95% CI: 1.061 to 3.532, P=0.031). However, the operation time in the robotic-assisted group was 54 minutes longer (95% CI: 20.489 to 87.037, P=0.002) than laparoscopic group. In addition, the robotic-assisted group had a lower open conversion rate (OR=0.324, 95% CI: 0.129 to 0.816, P=0.017) and a shorter length of hospital stay (WMD=-1.127, 95% CI: -2.071 to -0.184, P=0.019). CONCLUSION: Robot-assisted surgery offered several advantages over laparoscopic surgery for locally advanced mid-low rectal cancer following NCRT in terms of resection of lower tumours with improved TME completeness, lower open conversion rate and shorter hospital stay, despite longer operative time.

3.
Heliyon ; 10(11): e32406, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38933947

ABSTRACT

Objective: The incidence of Crohn's disease (CD) and rheumatoid arthritis (RA) co-morbidity, as well as the number of individuals affected, is on the rise due to their shared molecular and cellular factors. This study aimed to identify potential therapeutic targets and medicines for comorbid CD and RA. Methods: We integrated single-cell RNA sequencing, Mendelian randomization, and colocalization analysis results from public databases to analyse immune cell subgroups in CD and RA patients and identify candidate therapeutic targets. We further screened potential medicines for the identified candidate targets using the Comparative Toxicogenomics Database (CTD) and molecular docking and molecular dynamics simulations. Results: The proportion of CD8 effector memory T cells (Tem) was consistently elevated in the peripheral blood mononuclear cells (PBMCs) of both CD and RA patients. MYBL1 had a causal effect on the onset of both CD (OR = 1.23; 95 % CI, 1.05-1.45; P = 0.046) and RA (OR = 1.45; 95 % CI, 1.14-1.85; P = 0.04). Four potential therapeutic molecules were retrieved from the CTD database, among which tretinoin (docking score: -6.3 kcal/mol) showed the best potential. Conclusion: Our comprehensive analysis suggests that CD8 Tem cells are a key cell group in comorbid RA and CD and that MYBL1 has a causal effect. Tretinoin was identified as a potential targeted therapeutic drug, which is of great clinical research value.

4.
Genomics ; 116(5): 110883, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38857813

ABSTRACT

Pigmented potato tubers are abundant in chlorogenic acids (CGAs), a metabolite with pharmacological activity. This article comprehensively analyzed the transcriptome and metabolome of pigmented potato Huaxingyangyu and Jianchuanhong at four altitudes of 1800 m, 2300 m, 2800 m, and 3300 m. A total of 20 CGAs and intermediate CGA compounds were identified, including 3-o-caffeoylquinic acid, 4-o-caffeoylquinic acid, and 5-o-caffeoylquinic acid. CGA contents in Huaxinyangyu and Jianchuanhong reached its maximum at an altitude of 2800 m and slightly decreased at 3300 m. 48 candidate genes related to the biosynthesis pathway of CGAs were screened through transcriptome analysis. Weighted gene co-expression network analysis (WGCNA) identified that the structural genes of phenylalanine deaminase (PAL), coumarate-3 hydroxylase (C3H), cinnamic acid 4-hydroxylase (C4H) and the transcription factors of MYB and bHLH co-regulate CGA biosynthesis. The results of this study provide valuable information to reveal the changes in CGA components in pigmented potato at different altitudes.

5.
Quant Imaging Med Surg ; 14(6): 3939-3950, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38846289

ABSTRACT

Background: Intestinal lipoma is considered the most common benign tumor that causes intussusception. This retrospective case-control study aimed to present the clinical and multidetector computed tomography (MDCT) features between intestinal lipomas with and without intussusception and examine risk factors that predict intussusception caused by intestinal lipomas. Methods: We retrospectively analyzed 281 adult patients diagnosed with intestinal lipoma by radiologists using whole-abdominal MDCT between January 2015 and August 2022. Patients were divided into adult intussusception (AI) and non-AI groups based on MDCT images. Univariate logistic regression was performed to identify risk factors for intestinal lipoma-induced intussusception. Results: A total of 281 patients with intestinal lipomas were included in the study, with an average age of 68.0±11.3 years, and the male to female ratio was about 1:1.4. Among them, 24 patients developed lipoma-induced intussusception. Patients in the AI group presented with more abdominal pain (70.8% vs. 47.1%, P=0.03), nausea/vomiting (37.5% vs. 14.8%, P=0.009), hematochezia/melena (29.2% vs. 11.3%, P=0.02), and abdominal tenderness (66.7% vs. 24.9%, P<0.001). Lipomas were more common in the small bowel (224/281, 79.7%) than the large bowel (57/281, 20.3%). Lipomas in the AI group showed more heterogeneous hypodensity (41.7% vs. 15.6%, P=0.004), longer length (median, 2.2 vs. 1.2 cm, P<0.001), and larger volume (median, 4.1 vs. 0.6 cm3, P<0.001). In the univariate logistic regression, lipoma density [odds ratio (OR) =3.875, 95% confidence interval (CI): 1.609-9.331, P=0.003] and lipoma length (OR =3.216, 95% CI: 1.977-5.231, P<0.001) were risk factors for intestinal lipoma-induced intussusception. Conclusions: More patients in the AI group have digestive tract symptoms than those in the non-AI group. Lipoma density and length are risk factors for intussusception in patients with intestinal lipoma. In addition, the common site of intestinal lipoma may have changed from the colon to the small intestine.

6.
J Control Release ; 372: 403-416, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38914207

ABSTRACT

The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

7.
BMC Genomics ; 25(1): 283, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500027

ABSTRACT

MYB transcription factors play an extremely important regulatory role in plant responses to stress and anthocyanin synthesis. Cloning of potato StMYB-related genes can provide a theoretical basis for the genetic improvement of pigmented potatoes. In this study, two MYB transcription factors, StMYB113 and StMYB308, possibly related to anthocyanin synthesis, were screened under low-temperature conditions based on the low-temperature-responsive potato StMYB genes family analysis obtained by transcriptome sequencing. By analyzed the protein properties and promoters of StMYB113 and StMYB308 and their relative expression levels at different low-temperature treatment periods, it is speculated that StMYB113 and StMYB308 can be expressed in response to low temperature and can promote anthocyanin synthesis. The overexpression vectors of StMYB113 and StMYB308 were constructed for transient transformation tobacco. Color changes were observed, and the expression levels of the structural genes of tobacco anthocyanin synthesis were determined. The results showed that StMYB113 lacking the complete MYB domain could not promote the accumulation of tobacco anthocyanins, while StMYB308 could significantly promote the accumulation involved in tobacco anthocyanins. This study provides a theoretical reference for further study of the mechanism of StMYB113 and StMYB308 transcription factors in potato anthocyanin synthesis.


Subject(s)
Solanum tuberosum , Transcription Factors , Transcription Factors/metabolism , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Anthocyanins , Temperature , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Plants, Genetically Modified/genetics
8.
Curr Med Imaging ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38415435

ABSTRACT

PURPOSE: This study aimed to explore the similarities and differences in clinical presentations, multidetector computed tomographic (MDCT) features, and treatment of three types of adult intussusceptions based on location. METHODS: We retrospectively reviewed 184 adult patients with 192 intussusceptions. Depending on the location, intussusceptions were classified as enteric, ileocolic, and colonic types. The similarities and differences of clinical presentations, MDCT features, and treatment of three types of adult intussusception were compared. Meanwhile, the three types of intussusceptions were further divided into surgical and conservative groups based on the treatment. Uni- and multivariate logistic analyses were used to identify risk factors for intussusception requiring surgery. RESULTS: Enteric and ileocolic intussusceptions were mainly presented with abdominal pain (78.46% and 85.71%). Hematochezia/melena (64.29%) was the main symptom of colonic intussusception. On MDCT, ileocolic intussusceptions were longer in length and had more signs of intestinal necrosis (hypodense layer, fluid collection and no/poor bowel wall enhancement) than enteric and colonic intussusceptions. Moreover, it was found that 93.88% (46/49) of ileocolic intussusception and 98.59% (70/71) of colonic intussusception belonged to the surgical group, whereas only 43.06% (31/72) of enteric intussusception belonged to the surgical group. Intussusception length (OR=1.171, P=0.028) and discernible lead point on MDCT (OR=21.003, P<0.001) were reliable indicators of enteric intussusception requiring surgery. CONCLUSION: Ileocolic intussusception may be more prone to intestinal necrosis than enteric and colonic intussusceptions, requiring more attention from clinicians. Surgery remains the treatment of choice for most ileocolic and colonic intussusceptions. Less than half of enteric intussusceptions require surgery, and MDCT features are effective in identifying them.

9.
Brain Imaging Behav ; 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38407737

ABSTRACT

We investigated abnormal functional connectivity (FC) patterns of insular subregions in patients with minimal hepatic encephalopathy (MHE) and examined their relationships with cognitive dysfunction using resting-state functional magnetic resonance imaging (fMRI). We collected resting-state fMRI data in 54 patients with cirrhosis [20 with MHE and 34 without MHE (NHE)] and 25 healthy controls. After defining six subregions of insula, we mapped whole-brain FC of the insular subregions and identified FC differences through three groups. FC of the insular subregions was correlated against clinical parameters (including venous blood ammonia level, Child-Pugh score, and cognitive score). The discrimination performance between the MHE and NHE groups was evaluated by performing a classification analysis using the FC index. Across three groups, the observed FC differences involved four insular subregions, including the left-ventral anterior insula, left-dorsal anterior insula, right-dorsal anterior insula, and left-posterior insula (P < 0.05 with false discovery rate correction). Moreover, the FC of these four insular subregions progressively attenuated from NHE to MHE. In addition, hypoconnectivity of insular subregions was correlated with the poor neuropsychological performance and the evaluated blood ammonia levels in patients (P < 0.05 with Bonferroni correction). The FC of insular subregions yielded moderate discriminative value between the MHE and NHE groups (AUC = 0.696-0.809). FC disruption of insular subregions is related to worse cognitive performance in MHE. This study extended our understanding about the neurophysiology of MHE and may assist for its diagnosis.

10.
Cereb Cortex ; 34(2)2024 01 31.
Article in English | MEDLINE | ID: mdl-38365269

ABSTRACT

The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach. Dynamic functional connectivity across central executive network was calculated using sliding-window approach. Functional states were estimated by K-means clustering. Right dorsolateral prefrontal cortex metabolite ratios (i.e. glutamate and glutamine complex/total creatine, myo-inositol / total creatine, and choline / total creatine) were determined. Neurocognitive performance was determined by psychometric hepatic encephalopathy scores. Minimal hepatic encephalopathy patients had decreased myo-inositol / total creatine and choline / total creatine and increased glutamate and glutamine complex / total creatine in right dorsolateral prefrontal cortex (all P ≤ 0.020); decreased static functional connectivity between bilateral dorsolateral prefrontal cortex and between right dorsolateral prefrontal cortex and lateral-inferior temporal cortex (P ≤ 0.001); increased frequency and mean dwell time in state-1 (P ≤ 0.001), which exhibited weakest functional connectivity. Central executive network dynamic functional indices were significantly correlated with right dorsolateral prefrontal cortex metabolic indices and psychometric hepatic encephalopathy scores. Right dorsolateral prefrontal cortex myo-inositol / total creatine and mean dwell time in state-1 yielded best potential for diagnosing minimal hepatic encephalopathy. Dynamic functional disturbance in central executive network may contribute to neurocognitive impairment and could be correlated with metabolic disorder.


Subject(s)
Hepatic Encephalopathy , Humans , Hepatic Encephalopathy/complications , Hepatic Encephalopathy/diagnostic imaging , Magnetic Resonance Imaging/methods , Glutamine/metabolism , Creatine/metabolism , Liver Cirrhosis/complications , Liver Cirrhosis/metabolism , Glutamic Acid/metabolism , Inositol/metabolism , Choline/metabolism , Brain
11.
Biomed Pharmacother ; 173: 116323, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38401523

ABSTRACT

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/ß-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/metabolism , Ubiquitin-Specific Proteases/metabolism , Signal Transduction , Wnt Signaling Pathway , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition , Cell Proliferation
13.
CNS Neurosci Ther ; 30(2): e14616, 2024 02.
Article in English | MEDLINE | ID: mdl-38334027

ABSTRACT

AIMS: To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS). METHODS: This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion-weighted data were collected. We used state-of-the-art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior-parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo-cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation. RESULTS: In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni-corrected p < 0.05). NDI decreased in the bilateral thalamo-motor and thalamo-somatosensory tracts and in the right thalamo-posterior-parietal and thalamo-occipital tracts (Bonferroni-corrected p < 0.05). NDI reduction in the bilateral thalamo-motor tract (p = 0.017 and 0.009) and left thalamo-somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo-cortical tracts, NDI yielded a higher effect size during between-group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics. CONCLUSIONS: Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo-cortical connectivity in ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Neurites , Humans , Diffusion Tensor Imaging/methods , Amyotrophic Lateral Sclerosis/diagnostic imaging , Thalamus/diagnostic imaging , Neural Pathways/diagnostic imaging
14.
Bone Res ; 11(1): 56, 2023 10 26.
Article in English | MEDLINE | ID: mdl-37884520

ABSTRACT

Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21-/-) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21-/- and Ctsk-cre; Trim21f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/ß-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.


Subject(s)
Osteogenesis , Osteoporosis , Animals , Female , Humans , Mice , beta Catenin/genetics , Bone and Bones/metabolism , Cell Differentiation/genetics , Osteogenesis/genetics , Osteoporosis/genetics
15.
Neuroradiology ; 65(11): 1589-1604, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37486421

ABSTRACT

PURPOSE: To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). METHODS: Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. RESULTS: MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. CONCLUSION: MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.

16.
Cell Death Discov ; 9(1): 241, 2023 Jul 13.
Article in English | MEDLINE | ID: mdl-37443100

ABSTRACT

N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification of mammalian messenger RNA. The m6A modification affects multiple aspects of RNA metabolism, including processing, splicing, export, stability, and translation through the reversible regulation of methyltransferases (Writers), demethylases (Erasers), and recognition binding proteins (Readers). Accumulating evidence indicates that altered m6A levels are associated with a variety of human cancers. Recently, dysregulation of m6A methylation was shown to be involved in the occurrence and development of gastric cancer (GC) through various pathways. Thus, elucidating the relationship between m6A and the pathogenesis of GC has important clinical implications for the diagnosis, treatment, and prognosis of GC patients. In this review, we evaluate the potential role and clinical significance of m6A-related proteins which function in GC in an m6A-dependent manner. We discuss current issues regarding m6A-targeted inhibition of GC, explore new methods for GC diagnosis and prognosis, consider new targets for GC treatment, and provide a reasonable outlook for the future of GC research.

17.
Acta Pharmacol Sin ; 44(11): 2253-2264, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37311796

ABSTRACT

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.


Subject(s)
Influenza A Virus, H1N1 Subtype , Interferon Type I , Orthomyxoviridae Infections , Mice , Animals , Capsaicin/pharmacology , STAT3 Transcription Factor , Signal Transduction , Carrier Proteins , Virus Replication
18.
CNS Neurosci Ther ; 29(11): 3406-3415, 2023 11.
Article in English | MEDLINE | ID: mdl-37208946

ABSTRACT

AIMS: To investigate microstructural impairments of corticospinal tracts (CSTs) with different origins in amyotrophic lateral sclerosis (ALS) using neurite orientation dispersion and density imaging (NODDI). METHODS: Diffusion-weighted imaging data acquired from 39 patients with ALS and 50 controls were used to estimate NODDI and diffusion tensor imaging (DTI) models. Fine maps of CST subfibers originating from the primary motor area (M1), premotor cortex, primary sensory area, and supplementary motor area (SMA) were segmented. NODDI metrics (neurite density index [NDI] and orientation dispersion index [ODI]) and DTI metrics (fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) were computed. RESULTS: The patients with ALS showed microstructural impairments (reflected by NDI, ODI, and FA reductions and MD, AD, and RD increases) in CST subfibers, especially in M1 fibers, which correlated with disease severity. Compared with other diffusion metrics, NDI yielded a higher effect size and detected the greatest extent of CST subfibers damage. Logistic regression analyses based on NDI in M1 subfiber yielded the best diagnostic performance compared with other subfibers and the whole CST. CONCLUSIONS: Microstructural impairment of CST subfibers (especially those originating from M1) is the key feature of ALS. The combination of NODDI and CST subfibers analysis may improve diagnosing performance for ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Motor Cortex , White Matter , Humans , Amyotrophic Lateral Sclerosis/diagnostic imaging , Neurites , Diffusion Tensor Imaging/methods , Diffusion Magnetic Resonance Imaging , Motor Cortex/diagnostic imaging
19.
J Affect Disord ; 328: 238-244, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36806594

ABSTRACT

BACKGROUND: Adolescents with daytime sleepiness have been demonstrated to have a higher level of suicidal risk than those without. Currently, few studies had examined the pathway from daytime sleepiness to suicidal risk among female adolescents. This study aimed to explore the association among menstrual pain, daytime sleepiness, and suicidal risk among female adolescents in China. METHODS: Of 7072 adolescents who participated in the follow-up survey of Shandong Adolescents Behavior & Health Cohort (SABHC), 3001 were female adolescents who had begun to menstruate and included for the analysis. A structured self-administrated questionnaire was used to measure menstrual pain, daytime sleepiness, suicidal risk and demographic characteristics. Participants were first surveyed in November-December 2015 and resurveyed 1 year later. RESULTS: Of 3001 participants, 11.43 % had suicidal risk, 79.8 % experienced menstrual pain. Cross-lagged analysis showed that there was cause-and-effect relationship between menstrual pain and daytime sleepiness. Moderate (OR = 1.79, 95%CI: 1.22-2.63) and severe (OR = 2.73, 95%CI: 1.80-4.12) menstrual pain (follow-up) were associated with suicidal risk (follow-up). Daytime sleepiness (baseline: OR = 1.04, 95%CI: 1.02-1.06, follow-up: OR = 1.07, 95%CI: 1.05-1.09) had effects on suicidal risk (follow-up). Mediation analysis showed that menstrual pain played a partially mediating role between daytime sleepiness and suicidal risk, with the indirect effect being 0.002 (95%CI: 0.001-0.004). LIMITATIONS: All data were self-reported. CONCLUSIONS: Menstrual pain and daytime sleepiness had effects on each other, and they both were the risk factors of suicidal risk. Among female adolescents, the association between daytime sleepiness and suicidal risk could be partially mediated by menstrual pain. Releasing the menstrual pain of female adolescents with daytime sleepiness could reduce their suicidal risk.


Subject(s)
Disorders of Excessive Somnolence , Dysmenorrhea , Adolescent , Humans , Female , Male , Prospective Studies , Suicidal Ideation , Surveys and Questionnaires
20.
Eur J Radiol ; 160: 110692, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36640714

ABSTRACT

PURPOSE: To investigate the diagnostic performance of clinical manifestations and multidetector computed tomographic (MDCT) features in detecting predictors of malignant intussusception in adults. MATERIAL AND METHODS: We retrospectively reviewed 88 adults with 91 intussusceptions who were diagnosed by MDCT. Their clinical manifestations and MDCT features were reviewed and compared between the malignant and benign groups. Uni- and multivariate logistic regression analyses were used to identify independent predictors of malignant intussusception. RESULTS: There were 61 patients in the malignant group and 27 patients in the benign group. The malignant group had older age (mean, 62.61 vs 54.22 years, P = 0.014), more colon-related intussusception (89.06% vs 55.56%, P < 0.001), shorter intussusception length (median, 6.53 vs 9.73 cm, P = 0.009), higher maximum short axis diameter (mean, 4.85 vs 4.10 cm, P = 0.001), more enlarged lymph nodes (40.63% vs 11.11%, P = 0.006) than the benign group. Lead points were mainly presented as masses, which were irregular (44.74%) and lobular (28.95%) in the malignant group, and round or oval (92.00%) in the benign group. On the unenhanced MDCT, 90.62% of them in the malignant group showed non-hypodense. Multivariate analysis showed that intussusception length (P = 0.013), maximum short axis diameter (P = 0.007), non-round/oval lead point (P < 0.001) and non-hypodense lead point (P = 0.030) were independent factors of malignant intussusception. CONCLUSION: Malignant intussusception can be identified using independent predictors such as intussusception length, maximum short axis diameter, non-round/oval and non-hypodense lead point. When integrating these four factors, radiologists can make qualitative diagnoses withhigher sensitivity and specificity, allowing clinicians to develop more appropriate treatments.


Subject(s)
Intussusception , Humans , Adult , Intussusception/diagnostic imaging , Intussusception/therapy , Retrospective Studies , Diagnosis, Differential , Multidetector Computed Tomography , Sensitivity and Specificity
SELECTION OF CITATIONS
SEARCH DETAIL
...