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1.
Ital J Pediatr ; 50(1): 109, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831339

ABSTRACT

BACKGROUND: Acute bulbar palsy-plus (ABPp) syndrome is an unusual variant of Guillain-Barré syndrome (GBS). Anti-GT1a and anti-GQ1b antibodies have been reported in patients with ABPp, but without reports related to GD3 antibodies. METHODS: Clinical data of a patient diagnosed as ABPp syndrome were reviewed clinically. And we summarized the GBS patients with ABP and facial paralysis reported in the literature. RESULTS: We reported a 13-year-old girl presented with asymmetric bifacial weakness, bulbar palsy and transient limb numbness, and had positive serum IgG anti-GD3 antibody. Through reviewing the GBS patients with ABP and facial paralysis reported previously, we found that facial palsy could be unilateral or bilateral. The bilateral facial palsy could present successively or simultaneously, and could be symmetrical or asymmetrical. Other common symptoms included ophthalmoplegia, sensory abnormality and ataxia. IgG anti-GT1a and IgG anti-GQ1b antibodies were the most frequent. Most of the patients had full recovery within two weeks to one year of follow-up. CONCLUSIONS: We reported a patient with asymmetric bifacial palsy and bulbar palsy, which seemed to fit the diagnosis of ABPp syndrome. This was the first report of ABPp variant of GBS with positive serum ganglioside GD3 IgG antibody.


Subject(s)
Gangliosides , Guillain-Barre Syndrome , Immunoglobulin G , Humans , Female , Gangliosides/immunology , Adolescent , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/immunology , Guillain-Barre Syndrome/blood , Immunoglobulin G/blood , Immunoglobulin G/immunology , Autoantibodies/blood
2.
J Coll Physicians Surg Pak ; 34(5): 584-594, 2024 May.
Article in English | MEDLINE | ID: mdl-38720221

ABSTRACT

The purpose of this meta-analysis was to conduct a comparative analysis of clinical scores and complication rates among patients experiencing recurrent patellar dislocation who underwent medial patellofemoral ligament (MPFL) reconstruction using both single and double tunnel techniques. A comprehensive search was conducted across electronic databases including PubMed, the Cochrane Library, Web of Science, and Google Scholar to retrieve articles relevant to MPFL reconstruction utilising the tunnel technique. Subsequently, meta-analyses were undertaken to assess complication rates and changes in clinical scores before and after surgery. Following this, sensitivity analysis and meta-regression analysis were performed to scrutinise potential confounding variables. A total of thirty-two studies were included in the analysis, comprising twenty-seven non-comparative studies and five comparative studies. The findings revealed a similarity in postoperative complication rates between the single and double tunnel fixation techniques: [9.0% (95%CI, 4.0%-15.6%) versus 8.9% (95%CI, 4.7%-14.1%, p = 0.844)]. Likewise, no statistically significant differences were observed in Lysholm scores [34.1 (95%CI, 26.7-41.5) versus 33.8 (95%CI, 27.7-40.0, p = 0.956)], Kujala scores [29.4 (95%CI, 22.3-36.4) versus 27.3 (95%CI, 22.3-32.3, p = 0.637)], and Tegner score change [1.1 (95%CI, 0.8-1.4) versus 0.7 (95%CI, -0.2-1.6, p = 0.429)] before and after MPFL reconstruction, respectively, using these two techniques. In conclusion, the authors found that the clinical functional improvement and complication rates in MPFL reconstruction using the single tunnel fixation technique are comparable to those achieved with the double tunnel fixation approach. However, to further advance the understanding in this field, additional randomised controlled studies must be conducted to provide further insights. Key Words: MPFL reconstruction, Bone tunnel, Patellar dislocation, Meta-analysis.


Subject(s)
Patellar Dislocation , Patellofemoral Joint , Plastic Surgery Procedures , Humans , Patellar Dislocation/surgery , Plastic Surgery Procedures/methods , Patellofemoral Joint/surgery , Treatment Outcome , Ligaments, Articular/surgery , Postoperative Complications/epidemiology , Patellar Ligament/surgery
4.
Reprod Biol Endocrinol ; 22(1): 58, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778410

ABSTRACT

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.


Subject(s)
Aneuploidy , Blastocyst , Deep Learning , Preimplantation Diagnosis , Humans , Retrospective Studies , Female , Preimplantation Diagnosis/methods , Adult , Pregnancy , Blastocyst/cytology , Genetic Testing/methods , Fertilization in Vitro/methods
5.
Int J Ophthalmol ; 17(3): 473-479, 2024.
Article in English | MEDLINE | ID: mdl-38721502

ABSTRACT

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

6.
Mil Med Res ; 11(1): 22, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622688

ABSTRACT

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.


Subject(s)
Ferroptosis , Reperfusion Injury , Animals , Mice , Dichlorodiphenyl Dichloroethylene , Hepatocytes , Interferon-alpha , RNA , RNA, Messenger
7.
Chem Commun (Camb) ; 60(38): 5086-5089, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38639097

ABSTRACT

Iridium-catalyzed dearomative allylation/acyl transfer rearrangement has been developed using easily available 2-pyridinyl benzoates and vinyl ethylene carbonate. This protocol enabled the expedient synthesis of a variety of chiral N-substituted 2-pyridones in good to high yields with excellent enantioselectivity. It has the advantages of high atom economy, wide substrate scope, gram-scale synthesis, and versatile synthetic transformations.

8.
Article in English | MEDLINE | ID: mdl-38551057

ABSTRACT

AIMS: The aim of this study is to explore the anti-depressant mechanism of Chaihu- Shugan San based on serum medicinal chemistry and network pharmacology methods. BACKGROUND: Depression lacks effective treatments, with current anti-depressants ineffective in 40% of patients. Chaihu-Shugan San (CHSGS) is a well-known traditional Chinese medicine compound to treat depression. However, the chemical components and the underlying mechanisms targeting the liver and brain in the anti-depressant effects of CHSGS need to be elucidated. METHODS: The chemical components of CHSGS in most current network pharmacology studies are screened from TCMSP and TCMID databases. In this study, we investigated the mechanism and material basis of soothing the liver and relieving depression in the treatment of depression by CHSGS based on serum pharmacochemistry. The anti-depressant mechanism of CHSGS was further verified by proteomics and high-throughput data. RESULTS: Through serum medicinal chemistry, we obtained 9 bioactive substances of CHSGS. These ingredients have good human oral bioavailability and are non-toxic. Based on liver ChIPseq data, CHSGS acts on 8 targets specifically localized in the liver, such as FGA, FGB, and FGG. The main contributors to CHSGS soothing the liver qi targets are hesperetin, nobiletin, ferulic acid, naringin and albiflorin. In addition, network pharmacology analysis identified 9 blood components of CHSGS that corresponded to 63 anti-depressant targets in the brain. Among them, nobiletin has the largest number of anti-depressant targets, followed by glycyrrhizic acid, ferulic acid, albiflorin and hesperetin. We also validated the anti-depressant mechanism of CHSGS based on hippocampal proteomics. CHSGS exerts anti-depressant effects on synaptic structure and neuronal function by targeting multiple synapse related proteins. CONCLUSION: This study not only provides a theoretical basis for further expanding the clinical application of CHSGS, but also provides a series of potential lead compounds for the development of depression drugs.

10.
Mol Psychiatry ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38486049

ABSTRACT

Combinatorial expression of postsynaptic proteins underlies synapse diversity within and between neuron types. Thus, characterization of neuron-type-specific postsynaptic proteomes is key to obtaining a deeper understanding of discrete synaptic properties and how selective dysfunction manifests in synaptopathies. To overcome the limitations associated with bulk measures of synaptic protein abundance, we developed a biotin proximity protein tagging probe to characterize neuron-type-specific postsynaptic proteomes in vivo. We found Shank3 protein isoforms are differentially expressed by direct and indirect pathway spiny projection neurons (dSPNs and iSPNs). Investigation of Shank3B-/- mice lacking exons 13-16 within the Shank3 gene, reveal distinct Shank3 protein isoform expression in iSPNs and dSPNs. In Shank3B-/- striatum, Shank3E and Shank3NT are expressed by dSPNs but are undetectable in iSPNs. Proteomic analysis indicates significant and selective alterations in the postsynaptic proteome of Shank3B-/- iSPNs. Correspondingly, the deletion of exons 13-16 diminishes dendritic spine density, reduces spine head diameter, and hampers corticostriatal synaptic transmission in iSPNs. Remarkably, reintroducing Shank3E in adult Shank3B-/- iSPNs significantly rectifies the observed dendritic spine morphological and corticostriatal synaptic transmission deficits. We report unexpected cell-type specific synaptic protein isoform expression which could play a key causal role in specifying synapse diversity and selective synapse dysfunction in synaptopathies.

11.
Cell Death Discov ; 10(1): 155, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538596

ABSTRACT

Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.

12.
Life Sci Alliance ; 7(5)2024 May.
Article in English | MEDLINE | ID: mdl-38453366

ABSTRACT

The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, although HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.


Subject(s)
Tumor Suppressor Protein p53 , Ubiquitin-Protein Ligases , Animals , Mice , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin/metabolism , Ubiquitination/genetics , Nuclear Proteins/metabolism , Signal Transduction/genetics , Mammals/metabolism
13.
iScience ; 27(4): 109136, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38510136

ABSTRACT

In neurons, it is commonly assumed that mitochondrial replication only occurs in the cell body, after which the mitochondria must travel to the neuron's periphery. However, while mitochondrial DNA replication has been observed to occur away from the cell body, the specific mechanisms involved remain elusive. Using EdU-labelling in mouse primary neurons, we developed a tool to determine the mitochondrial replication rate. Taking of advantage of microfluidic devices, we confirmed that mitochondrial replication also occurs locally in the periphery of neurons. To achieve this, mitochondria require de novo nuclear-encoded, but not mitochondrial-encoded protein translation. Following a proteomic screen comparing synaptic with non-synaptic mitochondria, we identified two elongation factors - eEF1A1 and TUFM - that were upregulated in synaptic mitochondria. We found that mitochondrial replication is impaired upon the downregulation of eEF1A1, and this is particularly relevant in the periphery of neurons.

14.
Crit Rev Immunol ; 44(4): 1-12, 2024.
Article in English | MEDLINE | ID: mdl-38505917

ABSTRACT

Stroke remained the leading cause of disability in the world, and the most important non-modifiable risk factor was age. The treatment of stroke for elder patients faced multiple difficulties due to its complicated pathogenesis and mechanism. Therefore, we aimed to identify the potential differentially expressed genes (DEGs) and singnalling pathways for aged people of stroke. To compare the DEGs in the aged rats with or without middle cerebral artery occlusion (MCAO) and to analyse the important genes and the key signaling pathways involved in the development of cerebral ischaemia in aged rats. The Gene Expression Omnibus (GEO) analysis tool was used to analyse the DEGs in the GSE166162 dataset of aged MCAO rats compared with aged sham rats. Differential expression analysis was performed in aged MCAO rats and sham rats using limma. In addition, the 74 DEGs (such as Fam111a, Lcn2, Spp1, Lgals3 and Gpnmb were up-regulated; Egr2, Nr4a3, Arc, Klf4 and Nr4a1 were down-regulated) and potential compounds corresponding to the top 20 core genes in the Protein-Protein Interaction (PPI) network was constructed using the STRING database (version 12.0). Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched. These DEGs were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the most significantly enriched pathway in aged MCAO rats. Moreover, innate immune response, the complement and coagulation cascades signaling pathway, the IL-17 and other signaling pathways were significantly correlated with the aged MCAO rats. Our study indicates that multiple genes and pathological processes involved in the aged people of stroke. The immune response might be the key pathway in the intervention of cerebral infarction in aged people.


Subject(s)
Infarction, Middle Cerebral Artery , Stroke , Rats , Humans , Animals , Aged , Infarction, Middle Cerebral Artery/genetics , Infarction, Middle Cerebral Artery/metabolism , Gene Expression Profiling , Resveratrol , Gene Expression , Membrane Glycoproteins/genetics
15.
Article in English | MEDLINE | ID: mdl-38432103

ABSTRACT

Conopomorpha sinensis Bradley is the most detrimental pest to litchi and longan in China. Adult eclosion, locomotion, mating and oviposition of C. sinensis usually occur at night, regulated by a circadian rhythm. Nevertheless, our understanding of the linkages between adult circadian rhythms and clock genes remains inadequate. To address this gap, transcriptomic analysis was conducted on female and male heads (including antennae) of C. sinensis using the Illumina HiSeq 6000 platform to identify major circadian clock-related genes. The annotated sequences were analyzed by BLASTx, and candidate clock genes were classified based on conservation, predicted domain architectures, and phylogenetic analysis. The analysis revealed a higher conservation of these genes among the compared moths. Further, the expression profile analysis showed a significant spatiotemporal and circadian rhythmic accumulation of some clock genes during development. The candidate clock genes were predominantly expressed in the head, highlighting their crucial function in circadian rhythm regulation. Moreover, CsinPer, CsinTim1, and CsinCry1 displayed similar dynamic expressions with a peak expression level in the 4th age adults, suggesting their involvement in regulation of courtship and mating behaviors. The CsinPer and CsinTim1 mRNA oscillated strongly with a similar phase, containing a peak expression just before the female mating peak. This work will greatly contribute to understanding the circadian clock system of C. sinensis and provide valuable information for further studies of the molecular mechanisms involved in rhythmicity in fruit-boring pests.


Subject(s)
Circadian Clocks , Transcriptome , Animals , Circadian Clocks/genetics , Female , Insect Proteins/genetics , Male , Head , Moths/genetics , Moths/physiology , Phylogeny , Circadian Rhythm/genetics , Gene Expression Profiling
16.
Math Med Biol ; 41(1): 53-80, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38421157

ABSTRACT

Altay Prefecture, a typical arid region in northwestern China, has experienced the climate transition from warming-drying to warming-wetting since 1980s and has attracted widespread attention. Nonetheless, it is still unclear how climate change has influenced the distribution of vegetation in this region. In this paper, a reaction-diffusion model of the climate-vegetation system is proposed to study the impact of climate change (precipitation, temperature and carbon dioxide concentration) on vegetation patterns in Altay Prefecture. Our results indicate that the tendency of vegetation growth in Altay Prefecture improved gradually from 1985 to 2010. Under the current climate conditions, the increase of precipitation results in the change of vegetation pattern structures, and eventually vegetation coverage tends to be uniform. Moreover, we found that there exists an optimal temperature where the spot vegetation pattern structure remains stable. Furthermore, the increase in carbon dioxide concentration induces vegetation pattern transition. Based on four climate change scenarios of the Coupled Model Intercomparison Project Phase 6 (CMIP6), we used the power law range (PLR) to predict the optimal scenario for the sustainable development of the vegetation ecosystem in Altay Prefecture.


Subject(s)
Climate Change , Ecosystem , Carbon Dioxide , China , Temperature
17.
J Asian Nat Prod Res ; 26(1): 154-176, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38321773

ABSTRACT

Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults. Up to now, the chemotherapy approaches for GBM are limited. Therefore, more studies on identifying and exploring new chemotherapy drugs or strategies overcome the GBM are essential. Natural products are an important source of drugs against various human diseases including cancers. With the better understanding of the molecular etiology of GBM, the development of new anti-GBM drugs has been increasing. Here, we summarized recent researches of natural products for the GBM therapy and their potential mechanisms in details, which will provide new ideas for the research on natural products and promote developing drugs from nature products for GBM therapy.


Subject(s)
Biological Products , Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/drug therapy , Glioblastoma/pathology , Biological Products/pharmacology , Biological Products/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology
18.
Phytomedicine ; 126: 155372, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38382281

ABSTRACT

BACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCß knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCß knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-ß induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCß overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. RESULTS: PKCß was upregulated in the UUO model. Knockdown of PKCß mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCß in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCß, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCß was found to counteract the renoprotective efficacy of Sch A in vitro. CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCß and attenuating oxidative stress.


Subject(s)
Cyclooctanes , Kidney Diseases , Lignans , Polycyclic Compounds , Ureteral Obstruction , Mice , Animals , Transforming Growth Factor beta1/metabolism , Kidney Diseases/drug therapy , Kidney , Fibrosis , Ureteral Obstruction/pathology , Oxidative Stress
19.
Cell Rep ; 43(2): 113680, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38241148

ABSTRACT

Extracellular vesicles (EVs) facilitate intercellular communication by transferring cargo between cells in a variety of tissues. However, how EVs achieve cell-type-specific intercellular communication is still largely unknown. We found that Notch1 and Notch2 proteins are expressed on the surface of neuronal EVs that have been generated in response to neuronal excitatory synaptic activity. Notch ligands bind these EVs on the neuronal plasma membrane, trigger their internalization, activate the Notch signaling pathway, and drive the expression of Notch target genes. The generation of these neuronal EVs requires the endosomal sorting complex required for transport-associated protein Alix. Adult Alix conditional knockout mice have reduced hippocampal Notch signaling activation and glutamatergic synaptic protein expression. Thus, EVs facilitate neuron-to-neuron communication via the Notch receptor-ligand system in the brain.


Subject(s)
Extracellular Vesicles , Neurons , Animals , Mice , Ligands , Protein Transport , Signal Transduction , Mice, Knockout
20.
Orthop J Sports Med ; 12(1): 23259671231220904, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38274015

ABSTRACT

Background: Osteochondral injuries (OCIs) are common in patients with acute lateral patellar dislocation, which can produce both short- and long-;term adverse effects. However, the pattern of these injuries warrants further analysis, especially in relation to patient age. Purpose: To determine the overall prevalence of concomitant OCIs as well as the prevalence differences based on location and age after acute lateral patellar dislocations. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to July 20, 2022. All articles reporting the prevalence of OCI were included. The sample characteristics such as age, study design, magnetic resonance imaging diagnostic data, and the number of patients with OCI were extracted. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment. The overall and per-;site injury rates were calculated, and the prevalence was stratified by age-;group (≤16 and >16 years) and compared. Results: The systematic review included 39 studies involving 3354 patients. MINORS scores were 11.94 ± 1.98 and 16 ± 3.46 in the noncomparative and comparative studies, respectively. The overall prevalence of bone bruises and OCI was 89.6% (95% CI, 77.4%-97.7%) and 48.8% (95% CI, 39.0%-58.7%), respectively. In both overall and >16-year-old patients, the lateral femoral condyle (LFC) was the most common site of bone bruise (90.5% [95% CI, 84.0%-95.6%] and 91.5% [95% CI, 84.3%-96.9%], respectively); however, the medial patellar bruise was more common in patients ≤16 years (89.2% [95% CI, 82.9%-94.4%]). Among the pooled sites of OCI, the medial patella accounted for the largest proportion (36.9% [95% CI, 28.0%-46.3%]). OCIs were more common in patients >16 years (52.6% [95% CI, 39.4%-65.6%]) than in patients ≤16 years (46.6% [95% CI, 33.2%-60.3%]). Conclusion: Bone bruises on the LFC were most prevalent overall and in patients >16 years, whereas bone bruises on the medial patella were more prevalent in patients ≤16 years. OCIs were frequently seen in patients >16 years, with the most common site being the medial patella.

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