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1.
J Neurol ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35501502

RESUMO

BACKGROUND: The understanding of fatal familial insomnia (FFI), a rare neurodegenerative autosomal dominant prion disease, has improved in recent years as more cases were reported. This work aimed to propose new diagnostic criteria for FFI with optimal sensitivity, specificity, and likelihood ratio. METHODS: An international group of experts was established and 128 genetically confirmed FFI cases and 281 non-FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with two-round expert consultation: (1) Validation of the 2018 FFI criteria. (2) Diagnostic item selection according to statistical analysis and expert consensus. (3) Validation of the new criteria. RESULTS: The 2018 criteria for possible FFI had a sensitivity of 90.6%, a specificity of 83.3%, with a positive likelihood ratio (PLR) of 5.43, and a negative likelihood ratio (NLR) of 0.11; and the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, with a PLR of 11.77, and a NLR of 0.18. The new criteria included more specific and/or common clinical features, two exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had therefore reached a better sensitivity and specificity (92.2% and 96.1%, respectively), a PLR of 23.64 and a NLR of 0.08, whereas the probable FFI criteria showed a sensitivity of 90.6%, a specificity of 98.2%, with a PLR of 50.33 and a NLR of 0.095. CONCLUSIONS: We propose new clinical diagnostic criteria for FFI, for a better refining of the clinical hallmarks of the disease that ultimately would help an early recognition of FFI and a better differentiation from other prion diseases.

2.
Clinics (Sao Paulo) ; 77: 100040, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35525225

RESUMO

OBJECTIVES: Accurate prognosis assessment across the heterogeneous population of brain metastases is very important, which may facilitate clinical decision-making and appropriate stratification of future clinical trials. Previous studies have shown the L1 Cell Adhesion Molecule (L1CAM) is potentially involved in human malignancies of multiple different samples and unfavorable survival. However, no data of L1CAM are available for the brain metastases from lung adenocarcinoma, especially for the one with neurosurgical resection. METHOD: The authors investigated the L1CAM expression in cranial metastatic lesions for patients with brain metastases from lung adenocarcinoma after neurosurgical resection using tissue microarrays that were obtained from the Department of Neurosurgery at the Cancer Hospital of the Chinese Academy of Medical Sciences. Furthermore, the relationship between L1CAM expression and clinic-pathological parameters, including overall survival time, was analyzed to assess the prognostic value of L1CAM. RESULTS: L1CAM high expression was found in 62.30% of brain metastases from lung adenocarcinoma and significantly correlated with brain metastasis number (p = 0.028) and Lung-molGPA score (p = 0.042). Moreover, L1CAM expression was an independent predictor of survival for brain metastases after neurosurgical resection in a multivariate analysis. Patients with L1CAM high expression had unfavorable overall survival time (p = 0.016). In addition, the multivariate analysis also showed age and extracranial transfer were also the independent prognostic factors for this type of patient with brain metastases. CONCLUSIONS: A subset of brain metastases from lung adenocarcinoma aberrantly expresses L1CAM. L1CAM is a novel independent prognostic factor for brain metastasis from lung adenocarcinoma after neurosurgical resection.

3.
J Diabetes Res ; 2022: 5779210, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493607

RESUMO

Purpose: To predict visual acuity (VA) 1 month after anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema (DME) by using machine learning. Methods: This retrospective study included 281 eyes with DME receiving intravitreal anti-VEGF treatment from January 1, 2019, to April 1, 2021. Eighteen features from electronic medical records and measurements data from OCT images were extracted. The data obtained from January 1, 2019, to November 1, 2020, were used as the training set; the data obtained from November 1, 2020, to April 1, 2021, were used as the validation set. Six different machine learning algorithms were used to predict VA in patients after anti-VEGF therapy. After the initial detailed investigation, we designed an optimization model for convenient application. The VA predicted by machine learning was compared with the ground truth. Results: The ensemble algorithm (linear regression + random forest regressor) performed best in VA and VA variance predictions. In the validation set, the mean absolute errors (MAEs) of VA predictions were 0.137-0.153 logMAR (within 7-8 letters), and the mean square errors (MSEs) were 0.033-0.045 logMAR (within 2-3 letters) for the 1-month VA predictions, respectively. For the prediction of VA variance at 1 month, the MAEs were 0.164-0.169 logMAR (within 9 letters), and the MSEs were 0.056-0.059 logMAR (within 3 letters), respectively. Conclusions: Our machine learning models could accurately predict VA and VA variance in DME patients receiving anti-VEGF therapy 1 month after, which would be much valuable to guide precise individualized interventions and manage expectations in clinical practice.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Aprendizado de Máquina , Edema Macular/tratamento farmacológico , Estudos Retrospectivos , Acuidade Visual
4.
Front Neurol ; 13: 832599, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493823

RESUMO

Introduction: Human gut dysbiosis has been implicated with the onset of many neurodegenerative disorders. However, the current data focused on the gut microbiota of patients with Creutzfeldt-Jakob disease (CJD) are still lacking. In our study, we explored the gut microbiota alteration in patients with CJD. Method: We performed 16S ribosomal RNA MiSeq sequencing in stool samples of patients with CJD and controls. Functional analysis of the gut microbiota between these two groups was based on Kyoto Encyclopedia of Genes and Genomes and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. Clinical rating scales were used to evaluate the association between cognitive impairment and gut microbiota alteration. Result: We identified a significant alteration in both the structure and the richness of the CJD group. Function analysis revealed that the gut microbiota of patients with CJD enriched in immune signaling molecule interactions and xenobiotics biodegradation. MoCA and survival times were found to be associated with gut microbiota in patients with CJD. Conclusion: We demonstrated an altered gut microbiota in patients with CJD, which was associated with the cognitive impairment and the survival time of these patients.

5.
Front Surg ; 9: 871776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495763

RESUMO

Background: Ecchymosis is one of the worrisome complications after total knee arthroplasty (TKA) and interferes with functional rehabilitation. Current clinical guidelines do not provide individualized approaches for patients with ecchymoses. Methods: In this study, we used thromboelastography (TEG) to determine the coagulation state after TKA and to then explore markers that predict the occurrence of ecchymosis events after TKA. In our cohort, patients were divided into ecchymosis (n = 55) and non-ecchymosis (n = 137) groups according to whether ecchymosis events occurred after TKA. Rivaroxaban 10 mg/d was taken orally for thromboprophylaxis after surgery. All patients completed TEG testing. Correlation analysis was used to determine the risk factors for ecchymosis after TKA, and receiver operating characteristic (ROC) curves for variables with significant correlation were plotted. Results: In all, 55 of the 192 patients (28.65%) developed ecchymosis surrounding the surgical site. Multivariate analysis showed that hidden blood loss (OR = 1.003 and p = 0.005) and changes in the coagulation index (ΔCI) values (OR = 0.351 and p = 0.001) were risk factors for ecchymosis after TKA. Using the Youden index, 0.1805 was determined as the optimal threshold value of ΔCI for predicting the occurrence of ecchymosis, with a sensitivity of 74.55% and specificity of 72.99%. ΔCI is a promising marker as an alarm for the occurrence of ecchymosis after TKA. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800017245). Registered name: The role of thrombelastography in monitoring the changes of coagulation function during perioperative period of arthroplasty. Registered 19 July 2018. http://www.chictr.org.cn/showproj.aspx?proj=29220.

6.
Sci Rep ; 12(1): 6625, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459923

RESUMO

Alzheimer's disease (AD) is the most common cause of progressive dementia. In the present study, we showed hippocampal tissue transcriptome analysis in APPswe/PSEN1dE9 (APP/PS1, AD model) mice treated with fasudil (ADF) and compared with AD mice treated with saline (ADNS) and wild type mice (WT). The competing endogenous RNA (ceRNA) network was constructed and validated the differential expression of mRNA, lncRNA, miRNA, and circRNA. Our study showed differentially expressed mRNAs (DEMs) between WT and ADNS, while enriched in cell growth and death and nervous system pathways. DEMs between ADNS-ADF were enriched in the nervous system, glycosaminoglycan biosynthesis-keratan sulfate (KS) and Quorum sensing pathways. We validated four genes with RT-PCR, whereas enrichment of Acyl-CoA Synthetase Long Chain Family Member 4 (Acsl4, ENSMUST00000112903) in Quorum sensing pathways, and BTG anti-proliferation factor 1 (Btg1, ENSMUST00000038377) in RNA degradation pathways were conducted. Expression of these two genes were higher in ADNS, but were significantly reduced in ADF. Histone H4 transcription factor (Hinfp, ENSMUST00000216508) orchestrate G1/S transition of mitotic cell cycle and co-expressed with mmu-miR-26a-2-3p-mediated ceRNA and mmu-miR-3065-5p-mediated ceRNA; Wnt family member 4 (Wnt4, ENSMUST00000045747) was enriched in mTOR, Hippo and Wnt signaling pathway. Expression of these two genes were significantly lower in ADNS, and fasudil treatment reverse it. The present studies demonstrated four genes: Acsl4, Btg1, Hinfp, Wnt4 could be potential biomarkers of AD and the targets of fasudil treatment. These results will pave a novel direction for future clinic studies for AD and fasudil treatment.


Assuntos
Doença de Alzheimer , MicroRNAs , RNA Longo não Codificante , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Transcriptoma
7.
J Clin Pharm Ther ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488449

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Patients with optic neuritis (ON) have significant individual differences in their response to high-dose intravenous methylprednisolone (HIMP) therapy. This study aims to evaluate the association between gene polymorphisms and the efficacy of HIMP therapy in Chinese Han patients with ON mediated by aquaporin-4 immunoglobulin G antibody (AQP4-IgG) -positive neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS). METHODS: Chinese Han patients with AQP4-IgG+ NMOSD-ON or MS-ON were genotyped for four candidate genes: ABCB1 (rs1045642, rs1128503, rs2032582), NR3C1 (rs41423247), TBX21 (rs9910408, rs16947078) and VDR (rs731236, rs1544410, rs7975232, rs2228570). Patients were divided into glucocorticoid resistance (GR) and glucocorticoid sensitivity (GS) groups based on vision acuity (VA) improvement after HIMP treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies and haplotype distributions. RESULTS: A total of 267 patients completed the follow-up, including 120 patients with AQP4-IgG+ NMOSD-ON and 147 patients with MS-ON. We observed a significant association between the ABCB1 G2677T/A (rs2032582) polymorphism and glucocorticoid response in AQP4-IgG+ NMOSD-ON patients. Changes in VA scores in patients with the GG genotype were significantly lower than those in patients with the T/A T/A genotype (1.07 ± 1.20 vs. 1.77 ± 1.31, p = 0.026). In the GS group, the G allele had a lower frequency than the T/A allele (32.03% vs. 60.16%, p = 0.001). Logistic regression analysis showed that the G2677T/A GG and G T/A genotypes could increase the GR risk 3.53 and 2.67 times compared with the T/A T/A genotype, respectively (OR = 3.534, 95% CI: 1.186-10.527, p = 0.023; OR = 2.675, 95% CI: 1.005-7.123, p = 0.049). In addition, haplotype analysis showed that AQP4-IgG+ NMOSD-ON patients with the TAT/TTT haplotype (ABCB1 C3435T-G2677T/A-C1236T) were only 0.54 times more likely to develop GR than those with other haplotypes (OR = 0.542, 95% CI: 0.315-0.932, p = 0.026). However, we did not observe intergroup differences in the MS-ON population. WHAT IS NEW AND CONCLUSION: Our findings suggest that the G > T/A polymorphism of ABCB1 G2677T/A and the TAT/TTT haplotype played a protective role in HIMP treatment of AQP4-IgG+ NMOSD-ON but not MS-ON.

8.
J Neuroophthalmol ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35482897

RESUMO

ABSTRACT: We report a case of pendular seesaw nystagmus caused by bitemporal hemianopia; the nystagmus disappeared while in darkness as previously described, but it also disappeared with monocular occlusion, which indicates the pivotal role of binocular vision in the pathogenesis.

9.
J Ethnopharmacol ; : 115302, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489661

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Platycladus orientalis seeds are recorded in traditional Chinese medicine (TCM) formulations for modulation of mood and physical activity in "Shen Nong Ben Cao Jing" and "Compendium of Materia Medica" and so on. Recently, we identified its extracting components and looked for the potentials in treatment for depression by improving the function of monoamine neurotransmitters. AIM OF THE STUDY: We investigated the mechanism of action of the seed extracts of P. orientalis (S4) to rescue depressive behavior in a chronic, unpredicted, mild stress (CUMS)-induced model in rats. MATERIALS AND METHODS: We used ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry to analyze the chemical constituents in S4. An assay platform in zebrafish and molecular docking were used to analyze if S4 regulated rest/wake behavior and predict the biological targets which correlated with monoamine neurotransmitters. Depressive-behavior tests (body weight, sucrose preference test, tail-suspension test, forced-swimming test) were carried in the CUMS model. After behavior tests and killing, rat brains were separated into the hippocampus, frontier cortex and dorsal raphe nucleus. The main monoamine neurotransmitters and their metabolite concentrations in these three brain regions were measured by rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry. RESULTS: Forty-one compounds were identified in S4, including fatty acids, terpenoids, amino acids, plant sterols and flavonoids. S4 could increase the total rest time and decrease the waking activity of zebrafish. S4 showed high correlation with adrenaline agonists, 5-hydroxytryptamine (5-HT) reuptake inhibitors and dopamine agonists. CUMS-group rats, compared with controls, had significantly decreased body weight and preference for sucrose water, whereas the immobility time in the tail-suspension test and forced-swimming test was increased. S4 could significantly rescue the increased levels of 5-HT, noradrenaline and dopamine in the prefrontal cortex and dorsal raphe nucleus. CONCLUSIONS: We demonstrated that S4 was a potential inhibitor of MAO reuptake that could rescue depression in a CUMS-model rats by restoring monoamine neurotransmitters in different encephalic regions.

10.
Invest Ophthalmol Vis Sci ; 63(4): 18, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35472217

RESUMO

Purpose: The transparency of the ocular lens is essential for refracting and focusing light onto the retina, and transparency is controlled by many factors and signaling pathways. Here we showed a critical role of chromatin remodeler zinc finger HIT-type containing 1 (Znhit1) in maintaining lens transparency. Methods: To explore the roles of Znhit1 in lens development, the cre-loxp system was used to generate lens-specific Znhit1 knockout mice (Znhit1Mlr10-Cre; Znhit1 cKO). Morphological changes in mice lenses were examined using hematoxylin and eosin staining. RNA sequencing (RNA-seq) and assay for transposase accessible chromatin using sequencing (ATAC-seq) were applied to screen transcriptome changes. Immunofluorescence staining were performed to assess proteins distribution and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining were used for determining apoptosis. The mRNAs expression was examined by quantitative RT-PCR and proteins expression by Western blot. Results: Lens-specific conditional knockout mice had a severe cataract, microphthalmia phenotype, and seriously abnormal lens fiber cells differentiation. Deletion of Znhit1 in the lens resulted in decreased cell proliferation and increased cell apoptosis of the lens epithelia. ATAC-seq showed that Znhit1 deficiency increased chromatin accessibility of cyclin-dependent kinase inhibitors, including p57Kip2 and p21Cip1, and upregulated the expression of these genes in mRNA and protein levels. And we also showed that loss of Znhit1 lead to lens fibrosis by upregulating the expression of p21Cip1. Conclusions: Our findings suggested that Znhit1 is required for the survival of lens epithelial cells. The loss of Znhit1 leads to the overexpression of p21Cip1, further resulting in lens fibrosis, and impacted the establishment of lens transparency.


Assuntos
Cristalino , Animais , Proteínas de Transporte/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células , Cromatina , Fibrose , Cristalino/metabolismo , Camundongos , Camundongos Knockout
11.
Mol Med Rep ; 25(6)2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35475514

RESUMO

Osteoporosis is a systemic bone disease characterized by decreased bone mass and quality and bone micro­architecture degradation. Its primary cause is disorder of bone metabolism: Over­formation of osteoclasts, resulting in increased bone resorption and insufficient osteogenesis. Traditional herbal flavonoids can be used as alternative drugs to prevent and treat osteoporosis due to their wide range of sources, structural diversity and less adverse effects. The present paper reviewed six flavonoids, including quercetin, icariin, hesperitin, naringin, chrysin and pueraria, that promote bone formation and have been widely studied in the literature over the past five years, with the aim of providing novel ideas for the development of drugs for bone­associated disease.


Assuntos
Flavonoides , Osteoporose , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Osteoclastos , Osteogênese , Osteoporose/tratamento farmacológico , Quercetina/farmacologia
12.
Biochim Biophys Acta Mol Cell Res ; 1869(8): 119265, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35381294

RESUMO

Endoplasmic reticulum (ER) stress is an evolutionarily conserved cellular stress response related to multiple diseases, including temporomandibular joint (TMJ) cartilage-related diseases. Recent studies have indicated that DDIT3/CHOP (a downstream transcription factor of ER stress) is an important effector in mediating ER stress to inhibit chondrogenesis. However, the underlying mechanism by which DDIT3 regulates chondrogenesis remains unclear. In this study, tunicamycin (an ER stress agonist)-induced ER stress inhibited chondrocyte differentiation and matrix synthesis in vitro and led to an osteoarthritis-like phenotype in mouse TMJ cartilage. Meanwhile, DDIT3 expression in chondrocytes was robustly upregulated. Loss-of-function experiments validated the inhibiting effect of DDIT3 on chondrocyte differentiation and matrix synthesis. Mechanistically, the inhibiting effect was attributed to the direct and indirect regulatory effect of DDIT3 on SIRT1 (sirtuin1, silent mating type information regulation protein type 1, a member of NAD+ dependent class III histone deacetylases). On one hand, DDIT3 directly promoted the transcription of SIRT1. On the other hand, DDIT3 indirectly increased the expression of SIRT1 by promoting AMPKα phosphorylation and activation. Furthermore, activation of AMPKα or SIRT1 with the corresponding agonist AICAR or resveratrol in the DDIT3-knockdown cells partially restored the inhibiting effect of DDIT3 on chondrocyte differentiation and matrix synthesis. Collectively, these novel findings indicate that DDIT3 regulates the inhibitory effect of ER stress on chondrocyte differentiation and matrix synthesis partially via the AMPKα-SIRT1 pathway. A thorough understanding of ER stress in regulating chondrocyte homeostasis and its role in the onset of osteoarthritis may be promising to develop therapeutic targets and prevent condyle cartilage destruction.

13.
Oxid Med Cell Longev ; 2022: 1835900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432716

RESUMO

The purpose of this research was to observe the functions and mechanisms of ubiquitin-specific peptidase 7 (USP7) on chondrocytes under tumor necrosis factor alpha- (TNF-α-) induced inflammation. Knee osteoarthritis (OA) models of mice were constructed by anterior cruciate ligament transection. The knee joint of mice was observed by histological staining, and the expression of USP7 was measured by immunohistochemistry staining. After knocking down or inhibiting USP7, chondrocyte proliferation was measured by histological staining and the CCK-8 assay; apoptosis was measured by western blot, flow cytometry, Caspase-3 activity, and TUNEL staining; and inflammatory response was measured by qRT-PCR and ELISA. The 4-phenylbutyric acid (4-PBA), siRNA of CHOP (si-CHOP), and QNZ were used to verify the signaling pathways. It was found that USP7 was reduced in the knee joint cartilage of OA mice. The knockdown of USP7 or its inhibitor decreased chondrocyte proliferation and accelerated apoptosis and inflammatory response under inflammation. The USP7 inhibitor exacerbated cartilage destruction in mice with OA. The knockdown of USP7 or its inhibitor activated the BiP-eIF2α-ATF4-CHOP signaling of endoplasmic reticulum stress (ERS) and NF-κB/p65 signaling. 4-PBA, si-CHOP, and QNZ partly reversed chondrocyte proliferation, apoptosis, and inflammatory response caused by USP7 knockdown. In conclusion, through inhibiting the BiP-eIF2α-ATF4-CHOP signaling of ERS and NF-κB/p65 signaling, USP7 promotes chondrocyte proliferation and suppresses the apoptosis and inflammatory response under TNF-α-induced inflammation.


Assuntos
Estresse do Retículo Endoplasmático , NF-kappa B , Animais , Apoptose , Proliferação de Células , Condrócitos/metabolismo , Inflamação/patologia , Camundongos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Peptidase 7 Específica de Ubiquitina/metabolismo
14.
Nanomaterials (Basel) ; 12(7)2022 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-35407320

RESUMO

Surface-enhanced Raman spectroscopy (SERS) has long been an ultrasensitive technique for trace molecule detection. However, the development of a sensitive, stable, and reproducible SERS substrate is still a challenge for practical applications. Here, we demonstrate a cost-effective, centimeter-sized, and highly reproducible SERS substrate using the nanosphere lithography technique. It consists of a hexagonally packed Ag metasurface on a SiO2/Au/Si substrate. A seconds-lasting etching process of a self-assembled nanosphere mask manipulates the geometry of the deposited Ag metasurface on the SiO2/Au/Si substrate, which attains the wavelength matching between the optical absorbance of the Ag/SiO2/Au/Si substrate and the excitation laser wavelength as well as the enhancement of Raman signals. By spin-coating a thin layer of graphene oxide on the substrate, a SERS performance with 1.1 × 105 analytical enhancement factor and a limit of detection of 10-9 M for melamine is achieved. Experimental results reveal that our proposed strategy could provide a promising platform for SERS-based rapid trace detection in food safety control and environmental monitoring.

15.
Transl Oncol ; 20: 101423, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35429902

RESUMO

Gastric cancer (GC) is one of the most common human malignancies worldwide, but the molecular mechanism of GC has not been fully elucidated. Tetraspanin 31 (TSPAN31) has been rarely studied in human malignant tumors. This study aimed to investigate the effects of TSPAN31 on GC. We analyzed GC tissues through high-throughput sequencing technology and chose TSPAN31 with high expression. The expression of TSPAN31 in GC was analyzed through bioinformatics website and qRT-PCR. The protein level of TSPAN31 in GC tissues was determined by western blot and immunochemistry. The proliferation, migration, and apoptosis of GC cells were detected by the cell counting kit-8, transwell, and apoptosis experiments. METTL1 and CCT2 that may co-express with TSPAN31 were predicted by the GEPIA database, and analyzed the correlation between the expression levels of TSPAN31, METTL1 and CCT2. The results shows TSPAN31 was highly expressed in GC tissues, and high expression of TSPAN31 was found to result in poor prognosis of patients with GC. TSPAN31 could regulate the proliferation, migration and apoptosis of GC cells. The relative expression levels of TSPAN31, METTL1 and CCT2 in GC were positively correlated. Low expression of TSPAN31 could partially reverse the effect of high expression of METTL1 and CCT2 on the tumor progression of GC cells. In conclusion, TSPAN31 was highly expressed in GC tissues and led to poor prognosis of patients with GC. TSPAN31 may regulate the proliferation, migration, and apoptosis of GC cells. This regulatory mechanism may be achieved through co-expression with METTL1 and CCT2.

16.
Brain Res Bull ; 185: 39-48, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35452749

RESUMO

Remote ischemic postconditioning (RIPostC) is a protective procedure for brain damage caused by ischemia/reperfusion (IR), yet the mechanism of this treatment remains to be elucidated. Circular RNAs (circRNAs) are endogenous non-coding RNAs that have recently been recognized to play vital roles in ischemic brain injury. The aim of this study was to explore the role of circRNAs in the protective mechanism of RIPostC and to analyze the circRNA-microRNA (miRNA) regulation network in RIPostC. Nine rats were assigned randomly into three groups (three rats per group): sham, IR, and RIPostC. Their brain tissues were extracted for next-generation RNA sequencing and bioinformatics analysis was performed for two comparisons: sham vs. IR and IR vs. RIPostC. The expression patterns of selected circRNAs and miRNAs were validated by quantitative real-time PCR (qPCR). We detected 82 upregulated and 51 downregulated circRNAs and 137 upregulated and 127 downregulated miRNAs in the IR group compared with the sham group, and 41 upregulated and 100 downregulated circRNAs and 45 upregulated and 64 downregulated miRNAs in the RIPostC group compared with the IR group. The proposed competitive endogenous RNA (ceRNA) network, which included 24 circRNAs, 20 miRNAs, and 145 mRNAs, indicated that the dysregulated circRNAs played important roles in brain IR injury. On the basis of the expression patterns of selected circRNAs, miRNAs, and mRNAs obtained by qPCR, we proposed a circRNA_0002286-miR-124-3p-VLCAD pathway. In PC12 cell, the expression level of miR-124-3p was significantly upregulated when the expression of circRNA_0002286 was repressed and the expression level of VLCAD (very-long chain acyl-CoA dehydrogenase) was significantly downregulated, which suggested that circRNA_0002286 may act as a miRNA sponge for miR-124-3p to regulate the expression of VLCAD. We found that upregulation of circRNA_0002286 attenuated IR injury and was associated with downregulation of miR-124-3p and upregulation of VLCAD. This is the first time that circRNAs have been shown to be closely related to brain IR injury and RIPostC and suggests that targeting the circRNA_0002286-miR-124-3p-VLCAD pathway might attenuate brain IR injury.

17.
Vaccines (Basel) ; 10(4)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35455313

RESUMO

MHC-I antigen processes and presentation trigger host-specific anti-viral cellular responses during infection, in which epitope-recognizing cytotoxic T lymphocytes eliminate infected cells and contribute to viral clearance through a cytolytic killing effect. In this study, Hantaan virus (HTNV) GP-derived 9-mer dominant epitopes were obtained with high affinity to major HLA-I and H-2 superfamilies. Further immunogenicity and conservation analyses selected 11 promising candidates, and molecule docking (MD) was then simulated with the corresponding MHC-I alleles. Two-way hierarchical clustering revealed the interactions between GP peptides and MHC-I haplotypes. Briefly, epitope hotspots sharing good affinity to a wide spectrum of MHC-I molecules highlighted the biomedical practice for vaccination, and haplotype clusters represented the similarities among individuals during T-cell response establishment. Cross-validation proved the patterns observed through both MD simulation and public data integration. Lastly, 148 HTNV variants yielded six types of major amino acid residue replacements involving four in nine hotspots, which minimally influenced the general potential of MHC-I superfamily presentation. Altogether, our work comprehensively evaluates the pan-MHC-I immunoreactivity of HTNV GP through a state-of-the-art workflow in light of comparative immunology, acknowledges present discoveries, and offers guidance for ongoing HTNV vaccine pursuit.

18.
BMC Genomics ; 23(Suppl 1): 272, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392802

RESUMO

BACKGROUND: Transcription factors (TFs) play central roles in regulating gene expression. With the rapid growth in the use of high-throughput sequencing methods, there is a need to develop a comprehensive data processing and analyzing framework for inferring influential TFs based on ChIP-seq/ATAC-seq datasets. RESULTS: Here, we introduce FindIT2 (Find Influential TFs and Targets), an R/Bioconductor package for annotating and processing high-throughput multi-omics data. FindIT2 supports a complete framework for annotating ChIP-seq/ATAC-seq peaks, identifying TF targets by the combination of ChIP-seq and RNA-seq datasets, and inferring influential TFs based on different types of data input. Moreover, benefited from the annotation framework based on Bioconductor, FindIT2 can be applied to any species with genomic annotations, which is particularly useful for the non-model species that are less well-studied. CONCLUSION: FindIT2 provides a user-friendly and flexible framework to generate results at different levels according to the richness of the annotation information of user's species. FindIT2 is compatible with all the operating systems and is released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor ( https://bioconductor.org/packages/devel/bioc/html/FindIT2.html ).


Assuntos
Software , Fatores de Transcrição , Sequenciamento de Cromatina por Imunoprecipitação , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Fatores de Transcrição/genética
19.
Front Oncol ; 12: 865121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433455

RESUMO

Background: Growing evidence supports the modulatory role of human gut microbiome on neoadjuvant chemotherapy (NAC) efficacy. However, the relationships among the gut microbiome, tumor-infiltrating lymphocytes (TILs), and NAC response for breast cancer (BC) patients remain unclear. We thus proposed this preliminary study to investigate the relationship between gut microbiome and BC patients' responses to NAC treatment as well as underlying mechanisms. Methods: Prior to receiving NAC, the fecal metagenome collected from 23 patients with invasive BC was analyzed. Patients were subsequently assigned to the NAC non-effectual group and the NAC effectual group based on their response to NAC. The peripheral T lymphocyte subset counts were examined by flow cytometry methods. CellMinor analysis was employed to explore the relationship between CD4 mRNA expression and the reaction of tumor cells to NAC drugs. Results: The gut microbiomes of the NAC non-effectual group showed characteristics of low diversity with low abundances, distinct metagenomic composition with decreased butyrate-producing and indolepropionic acid-producing bacteria, and increased potential pathobionts compared with the NAC effectual group. The combination of Coprococcus, Dorea, and uncultured Ruminococcus sp. serves as signature bacteria for distinguishing NAC non-effectual group patients from the NAC effectual group. The absolute numbers of CD4+ and CD8+ TIL infiltration in tumors in the NAC non-effectual group were significantly lower than those in the effectual group. Similar findings were reported for the CD4+ T lymphocytes in the peripheral blood (p's < 0.05). NAC effectual-related signature bacteria were proportional to these patients' CD4+ T lymphocyte counts in peripheral blood and tumors (p's < 0.05). CellMinor analysis showed that the CD4 mRNA expression level dramatically climbed with increased sensitivity of tumor cells to NAC drugs such as cyclophosphamide, cisplatin, and carboplatin (p's < 0.05). Conclusions: The composition of the gut microbial community differs between BC patients for whom NAC is effective to those that are treatment resistant. The modulation of the gut microbiota on host CD4+ T lymphocytes may be one critical mechanism underlying chemosensitivity and NAC pathologic response. Taken together, gut microbiota may serve as a potential biomarker for NAC response, which sheds light on novel intervention targets in the treatment of NAC non-effectual BC patients.

20.
Front Surg ; 9: 843187, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356501

RESUMO

Background: Synovial fluid biomarkers have been found to improve the diagnosis of chronic periprosthetic joint infection (PJI); however, no "gold standard" exists yet. Interleukin-4 (IL-4) and polymorphonuclear cell (neutrophil) count in the synovial fluid are crucial in mediating local inflammation during bacterial infections and could be valuable biomarkers for PJI. Methods: This prospective study was conducted to investigate the diagnostic potential of synovial fluid IL-4 (SF-IL4) and polymorphonuclear cell percentage (SF-PMN%) for chronic PJI. A total of 110 patients who underwent revision arthroplasty between January 2019 and October 2020 were enrolled, and 11 patients were excluded. Of 99 patients, 43 were classified as having PJI and 56 as having aseptic failures according to the 2013 Musculoskeletal Infections Society criteria. In all patients, SF-IL4, SF-PMN%, serum C-reactive protein (CRP), and serum erythrocyte sedimentation rate (ESR) were quantified preoperatively. The diagnostic value for each biomarker was analyzed, and optimal cutoff values were calculated. Results: The patient demographics did not significantly vary. The area under the curve of SF-IL4 and SF-PMN% was 0.97 and 0.89, respectively, higher than that for serum ESR (0.72) and serum CRP (0.83). The combination of SF-IL4 and SF-PMN% provided higher specificity (97.0%) and accuracy (96.0%) when the cut-off values were 1.7 pg/mL and 75%, respectively. Conclusion: SF-IL4 is a valuable biomarker for chronic PJI detection, and the combination of SF-IL4 and SF-PMN% improved the diagnostic value of chronic PJI, and further studies are needed until its clinical application.

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