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1.
Brain Connect ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623770

RESUMO

PURPOSE: Persistent postural-perception dizziness (PPPD) is a chronic subjective form of dizziness characterized by the exacerbation of dizziness with active or passive movement, complex visual stimuli, and upright posture. Therefore, we aimed to analyze the resting-state functional magnetic resonance imaging (fMRI) in patients with PPPD using fractional amplitude of low-frequency fluctuation (fALFF) and voxel-mirrored homotopic connectivity (VMHC) and evaluate the correlation between abnormal regions in the brain and clinical features to investigate the pathogenesis of PPPD. METHODS: Thirty patients with PPPD (19 females and 11 males) and 30 healthy controls (HC) (18 females and 12 males) were closely matched for age and sex. The fALFF and VMHC methods were used to investigate differences in fMRI (BOLD sequences) between the PPPD and HC groups and to explore the associations between areas of functional abnormality and clinical characteristics (Dizziness, Anxiety, Depression, and Duration). RESULT: Compared to the HC group, patients with PPPD displayed different functional change patterns, with increased fALFF in the right precuneus and decreased VMHC in the bilateral precuneus. Additionally, patients with PPPD had a positive correlation between precuneus fALFF values and dizziness handicap inventory (DHI) scores, and a negative correlation between VMHC values and the disease duration. CONCLUSIONS: Precuneus dysfunction was observed in patients with PPPD. The fALFF values correlated with the degree of dizziness in PPPD, and changes in VMHC values were associated with the duration of dizziness, suggesting that fMRI changes in the precuneus of patients could be used as a potential imaging marker for PPPD.

2.
World J Gastrointest Oncol ; 16(3): 833-843, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577470

RESUMO

BACKGROUND: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary. AIM: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. METHODS: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. RESULTS: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor-node-metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant (P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). CONCLUSION: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

3.
Emerg Infect Dis ; 30(6)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640498

RESUMO

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

4.
Org Lett ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602315

RESUMO

A method was developed for the enantioselective formal 1,2-diamination of disubstituted ketenes using iminosulfinamides as nitrogen sources. The protocol involves the addition of lithium iminosulfinamides to ketenes to form N-iminosulfinyl amide metalloenolates. These metalloenolates then undergo a [2,3]-sigmatropic rearrangement to yield unnatural α,α-disubstituted α-amino acid derivatives with high enantiopurity. The chirality present at the sulfur atom in the iminosulfinamides is effectively transferred to α carbon of the resulting products, facilitating the highly enantioselective amination of ketenes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38451089

RESUMO

BACKGROUND AND OBJECTIVES: Accessing lesions in the posterior-medial thalamus can be challenging because of their deep location and intricate neurovascular anatomy. This study aims to describe the techniques and feasibility of the endoscopic supracerebellar infratentorial transpineal approach for treating posterior-medial thalamus lesions. METHODS: We reviewed and analyzed the clinical outcomes and endoscopic surgical experience of 11 patients with posterior-medial thalamic lesions. The first 4 cases used the endoscopic midline supracerebellar infratentorial transpineal approach, whereas the subsequent 7 cases used the endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach. All cases involved the upward transposition of the pineal gland to access the posterior-medial thalamus. The extent of resection and the endoscopic techniques were the main focus of analysis. Neurological examinations and MRI/computed tomography follow-up were conducted for 3-12 months after surgery. RESULTS: The pathology of the group included 6 gliomas, 1 cavernous malformation, 1 inflammation, 1 melanoma, and 2 hematomas. All 11 patients achieved gross total resection (6 patients, 54.5%) or subtotal resection (5 patients, 45.5%) with no new neurological deficits. Most patients (9 patients, 81.8%) experienced improvement in Karnofsky Performance Status after surgery. Postoperative hydrocephalus occurred in 2 patients (18.2%) and was relieved by endoscopic third ventriculostomy. CONCLUSION: The endoscopic supracerebellar infratentorial transpineal approach is an effective approach for removing posterior-medial thalamic lesions that require access through the third ventricle surfaces of the thalamus. The endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach provides a more superior and lateral view of the posterior-medial thalamic lesions.

6.
Appl Microbiol Biotechnol ; 108(1): 276, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536521

RESUMO

The massive usage of phthalate esters (PAEs) has caused serious pollution. Bacterial degradation is a potential strategy to remove PAE contamination. So far, an increasing number of PAE-degrading strains have been isolated, and the catabolism of PAEs has been extensively studied and reviewed. However, the investigation into the bacterial PAE uptake process has received limited attention and remains preliminary. PAEs can interact spontaneously with compounds like peptidoglycan, lipopolysaccharides, and lipids on the bacterial cell envelope to migrate inside. However, this process compromises the structural integrity of the cells and causes disruptions. Thus, membrane protein-facilitated transport seems to be the main assimilation strategy in bacteria. So far, only an ATP-binding-cassette transporter PatDABC was proven to transport PAEs across the cytomembrane in a Gram-positive bacterium Rhodococcus jostii RHA1. Other cytomembrane proteins like major facilitator superfamily (MFS) proteins and outer membrane proteins in cell walls like FadL family channels, TonB-dependent transporters, and OmpW family proteins were only reported to facilitate the transport of PAEs analogs such as monoaromatic and polyaromatic hydrocarbons. The functions of these proteins in the intracellular transport of PAEs in bacteria await characterization and it is a promising avenue for future research on enhancing bacterial degradation of PAEs. KEY POINTS: • Membrane proteins on the bacterial cell envelope may be PAE transporters. • Most potential transporters need experimental validation.


Assuntos
Ácidos Ftálicos , Ácidos Ftálicos/metabolismo , Proteínas de Membrana Transportadoras , Transportadores de Cassetes de Ligação de ATP/metabolismo , Bactérias/metabolismo , Ésteres , Dibutilftalato/química , China
7.
Mol Biol Rep ; 51(1): 292, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332381

RESUMO

BACKGROUND: Neuroinflammation contributes to both epileptogenesis and the associated neurodegeneration, so regulation of inflammatory signaling is a potential strategy for suppressing epilepsy development and pathological progression. Exosomes are enriched in microRNAs (miRNAs), considered as vital communication tools between cells, which have been proven as potential therapeutic method for neurological disease. Here, we investigated the role of miR129-5p-loaded mesenchymal stem cell (MSC)-derived exosomes in status epilepticus (SE) mice model. METHODS: Mice were divided into four groups: untreated control (CON group), kainic acid (KA)-induced SE groups (KA group), control exosome injection (KA + Exo-con group), miR129-5p-loaded exosome injection (KA + Exo-miR129-5p group). Hippocampal expression levels of miR129-5p, HMGB1, and TLR4 were compared among groups. Nissl and Fluoro-jade B staining were conducted to evaluate neuronal damage. In addition, immunofluorescence staining for IBA-1 and GFAP was performed to assess glial cell activation, and inflammatory factor content was determined by ELISA. Hippocampal neurogenesis was assessed by BrdU staining. RESULTS: The expression of HMGB1 was increased after KA-induced SE and peaking at 48 h, while hippocampal miR129-5p expression decreased in SE mice. Exo-miR129-5p injection reversed KA-induced upregulation of hippocampal HMGB1 and TLR4, alleviated neuronal damage in the hippocampal CA3, reduced IBA-1 + and GFAP + staining intensity, suppressed SE-associated increases in inflammatory factors, and decreased BrdU + cell number in dentate gyrus. CONCLUSIONS: Exosomes loaded with miR129-5p can protect neurons against SE-mediated degeneration by inhibiting the pro-inflammatory HMGB1/TLR4 signaling axis.


Assuntos
Exossomos , Proteína HMGB1 , MicroRNAs , Estado Epiléptico , Animais , Camundongos , Bromodesoxiuridina/efeitos adversos , Bromodesoxiuridina/metabolismo , Exossomos/metabolismo , Hipocampo/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Ácido Caínico/efeitos adversos , Ácido Caínico/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Neuroinflamatórias , Convulsões/genética , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/genética , Estado Epiléptico/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
8.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338975

RESUMO

Climate change-induced heat stress (HS) increasingly threatens potato (Solanum tuberosum L.) production by impacting tuberization and causing the premature sprouting of tubers grown during the hot season. However, the effects of post-harvest HS on tuber sprouting have yet to be explored. This study aims to investigate the effects of post-harvest HS on tuber sprouting and to explore the underlying transcriptomic changes in apical bud meristems. The results show that post-harvest HS facilitates potato tuber sprouting and negates apical dominance. A meticulous transcriptomic profiling of apical bud meristems unearthed a spectrum of differentially expressed genes (DEGs) activated in response to HS. During the heightened sprouting activity that occurred at 15-18 days of HS, the pathways associated with starch metabolism, photomorphogenesis, and circadian rhythm were predominantly suppressed, while those governing chromosome organization, steroid biosynthesis, and transcription factors were markedly enhanced. The critical DEGs encompassed the enzymes pivotal for starch metabolism, the genes central to gibberellin and brassinosteroid biosynthesis, and influential developmental transcription factors, such as SHORT VEGETATIVE PHASE, ASYMMETRIC LEAVES 1, SHOOT MERISTEMLESS, and MONOPTEROS. These findings suggest that HS orchestrates tuber sprouting through nuanced alterations in gene expression within the meristematic tissues, specifically influencing chromatin organization, hormonal biosynthesis pathways, and the transcription factors presiding over meristem fate determination. The present study provides novel insights into the intricate molecular mechanisms whereby post-harvest HS influences tuber sprouting. The findings have important implications for developing strategies to mitigate HS-induced tuber sprouting in the context of climate change.


Assuntos
Solanum tuberosum , Solanum tuberosum/metabolismo , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Amido/metabolismo , Tubérculos/metabolismo , Regulação da Expressão Gênica de Plantas
9.
Curr Mol Pharmacol ; 17: e18761429282063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389418

RESUMO

BACKGROUND: Nicosulfuron, a widely used herbicide in crops, has raised concerns due to its escalating presence as an environmental pollutant, particularly in soil and water. The potential adverse effects of nicosulfuron on animals, including reproductive toxicity, have garnered attention. OBJECTIVE: The study aimed to evaluate the reproductive toxicity of nicosulfuron in male mice. METHODS: Male mice were orally administrated with three different concentration gradients (350, 700, and 1400 mg/kg) of nicosulfuron for 35 days. The investigation delved into sperm quality, testicular structures, and expression of cleaved caspase-3 and NF-κB p65 of the testes. RESULTS: The finding unveiled a correlation between nicosulfuron exposure and detrimental effects on sperm quality and alteration of testicular structure. Notably, parameters, such as sperm survival rate (SUR) and sperm motility (MOT), exhibited a decline in relation to increasing nicosulfuron dosages. Moreover, in the mice subjected to higher doses of nicosulfuron, elevated expression of cleaved caspase-3 and NF-κB p65 was observed in the testes. Interestingly, we also observed an increase of NF-κB p65 expression in the mice exposed to the nicosulfuron. CONCLUSION: Our research revealed that exposure to nicosulfuron resulted in compromised sperm quality and alterations in testicular structure. The correlation between nicosulfuron and apoptosis, especially via the NF-κB pathway, provided significant insights into the mechanisms underpinning these detrimental effects. These findings significantly enhance our comprehension of the potential hazards associated with nicosulfuron exposure and its impacts on the reproductive health of animals.


Assuntos
NF-kappa B , Piridinas , Compostos de Sulfonilureia , Testículo , Masculino , Camundongos , Animais , NF-kappa B/metabolismo , Caspase 3/metabolismo , Caspase 3/farmacologia , Estresse Oxidativo , Motilidade dos Espermatozoides , Sêmen/metabolismo , Espermatozoides/metabolismo , Transdução de Sinais , Apoptose
10.
Adv Healthc Mater ; : e2302767, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381808

RESUMO

Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis. Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint. On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity. Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation. More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.

11.
World Neurosurg ; 182: e334-e343, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38052365

RESUMO

OBJECTIVE: The heterogeneity of the somatotroph adenomas, especially for sparsely granulated (SG) and densely granulated (DG) subtypes, has attracted great attention in identifying their imaging biomarker. The purpose of the current study was to compare the diagnostic performance of diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) sequences for preoperatively distinguishing the granulation patterns of somatotroph adenomas. METHODS: Thirty-two patients with a clinical diagnosis of somatotroph adenomas from October 2018 to March 2023 were included in this study. Coronal diffusion-weighted imaging (DWI) and T2-weighted MRI sequence data were collected from 3.0T MRI and compared between SG and DG groups. The immunohistochemistry was used to confirm the electron microscopy pathologic subtypes and Ki67 expression levels of somatotroph adenomas postoperatively. RESULTS: Patients in the SG group had significantly higher signal intensity (SI) ratio of DWI (rDWI) (P < 0.001), lower SI ratio of apparent diffusion coefficient (rADC) (P < 0.001), and higher SI ratio of T2-weighted imaging (P = 0.011). The combined diagnosis index of rDWI and rADC had the highest diagnostic efficiency in predicting SG adenomas (sensitivity, 93.3%; specificity, 88.2%; P < 0.001). The rDWI and rADC values had positive and negative correlations with the Ki67 index and tumor maximum diameter, respectively. Lower rADC×103 was an independent predictor for SG adenomas. CONCLUSIONS: Our results indicated that compared with previously used T2-weighted imaging, the DWI sequence, especially the combined diagnosis index of rDWI and rADC, could more efficiently distinguish the granulation patterns of somatotroph adenomas preoperatively.


Assuntos
Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Neoplasias Hipofisárias , Humanos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Antígeno Ki-67 , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/metabolismo , Imageamento por Ressonância Magnética , Imuno-Histoquímica , Neoplasias Hipofisárias/patologia
12.
World J Clin Cases ; 11(30): 7393-7397, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37969462

RESUMO

BACKGROUND: As left bundle branch pacing (LBBP) is more like physiological pacing, LBBP has emerged as a novel pacing strategy that uses the native conduction system to improve ventricular synchronization with stable pacing parameters. LBBP has been revealed associated with a significantly reduced risk of new-onset atrial fibrillation and heart failure compared with conventional permanent pacemaker implantation. CASE SUMMARY: A 64-year-old man was admitted with a 24-h history of chest distress and shortness of breath, which continued unabated. The patient had no symptoms of chest pain, dizziness, syncope, nausea nor vomiting. There were no abnormalities found in routine examinations after admission. Twelve-lead electrocardiogram presented a result of 2:1 atrioventricular block. Coronary angiography was performed the next day and no abnormality was found. Finally, the patient agreed to received LBBP and signed the informed consent. During the process of withdrawing the Medtronic Model 3830 lead into sheath, we found the lead helix was wrapped around the chordae tendineae of the septal valve of tricuspid. Attempts to rotate the 3830 lead failed to release the lead helix from the chordae tendineae, and ultimately we used radiofrequency ablation to ablate the wrapped chordae tendineae. CONCLUSION: Radiofrequency ablation effectively solved this problem without complications. It is an effective and reliable method to resolve lead winding chordae.

13.
Pain Physician ; 26(7): E805-E813, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37976487

RESUMO

BACKGROUND: Spinal cord stimulation is a technique in which different types of electrodes are placed in the spinal epidural space for neuromodulation. Surgical paddle electrodes (SEs) are usually implanted by a surgeon by performing open surgery with laminectomy. Recent advances in endoscopic spine surgery provide another option for minimally invasive SE implantation. OBJECTIVES: This anatomical study aims to examine the feasibility of implanting SEs in thoracic and cervical spine segments, discussing the specific advantages and disadvantages compared with previously reported methods. STUDY DESIGN: Laboratory study with Institutional Review Board No B2023-056. METHODS: Four fresh adult cadavers (2 women, 2 men) were operated on in this study. The posterior unilateral biportal endoscopic surgical approach, the accessibility to the intraspinal epidural space, and the technical possibilities and limitations of implantation of SEs were evaluated, as well as the surgical duration and complications. RESULTS: All the planned steps of the operation were successfully accomplished in all 4 cadavers. A total of 8 electrodes were successfully implanted through the working portal. Among them, 4 were located in the cervical segment and 4 in the thoracic segment. The proper position of the electrodes was also verified by fluoroscopy. No rupture of dura occurred during the operation. Except for the first cadaver, the duration of surgery did not exceed 1 hour. LIMITATIONS: Anatomical study on human cadavers, the quantity of cadavers, and the steep learning curve. CONCLUSIONS: The results of this anatomical study show that the SEs can be satisfactorily implanted in cervical and thoracic segments using the unilateral biportal endoscopic technique.


Assuntos
Estimulação da Medula Espinal , Masculino , Adulto , Humanos , Feminino , Estudos de Viabilidade , Espaço Epidural , Eletrodos Implantados , Cadáver , Medula Espinal/cirurgia
14.
J Neuroinflammation ; 20(1): 281, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012669

RESUMO

BACKGROUND: Inflammatory response triggered by innate immunity plays a pivotal element in the progress of ischemic stroke. Receptor-interacting kinase 2 (RIP2) is implicated in maintaining immunity homeostasis and regulating inflammatory response. However, the underlying mechanism of RIP2 in ischemic stroke is still not well understood. Hence, the study investigated the role and the ubiquitination regulatory mechanism of RIP2 in ischemic stroke. METHODS: Focal cerebral ischemia was introduced by middle cerebral artery occlusion (MCAO) in wild-type (WT) and OTUD1-deficient (OTUD1-/-) mice, oxygen glucose deprivation and reoxygenation (OGD/R) models in BV2 cells and primary cultured astrocytes were performed for monitoring of experimental stroke. GSK2983559 (GSK559), a RIP2 inhibitor was intraventricularly administered 30 min before MCAO. Mice brain tissues were collected for TTC staining and histopathology. Protein expression of RIP2, OTUD1, p-NF-κB-p65 and IκBα was determined by western blot. Localization of RIP2 and OTUD1 was examined by immunofluorescence. The change of IL-1ß, IL-6 and TNF-α was detected by ELISA assay and quantitative real-time polymerase chain reaction. Immunoprecipitation and confocal microscopy were used to study the interaction of RIP2 and OTUD1. The activity of NF-κB was examined by dual-luciferase assay. RESULTS: Our results showed upregulated protein levels of RIP2 and OTUD1 in microglia and astrocytes in mice subjected to focal cerebral ischemia. Inhibition of RIP2 by GSK559 ameliorated the cerebral ischemic outcome by repressing the NF-κB activity and the inflammatory response. Mechanistically, OTUD1 interacted with RIP2 and sequentially removed the K63-linked polyubiquitin chains of RIP2, thereby inhibiting NF-κB activation. Furthermore, OTUD1 deficiency exacerbated cerebral ischemic injury in response to inflammation induced by RIP2 ubiquitination. CONCLUSIONS: These findings suggested that RIP2 mediated cerebral ischemic lesion via stimulating inflammatory response, and OTUD1 ameliorated brain injury after ischemia through inhibiting RIP2-induced NF-κB activation by specifically cleaving K63-linked ubiquitination of RIP2.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Proteases Específicas de Ubiquitina , Animais , Camundongos , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/metabolismo , Inflamação/metabolismo , AVC Isquêmico/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
15.
J Exp Clin Cancer Res ; 42(1): 326, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38017479

RESUMO

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Camundongos Nus , Proliferação de Células/genética , Mitose , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proteínas Cromossômicas não Histona/metabolismo , Proteoglicanas de Sulfatos de Condroitina/genética , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas ras/metabolismo
16.
Front Neurosci ; 17: 1221579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901419

RESUMO

Objective: Benign paroxysmal positional vertigo (BPPV) is a common clinical vertigo disease, and the most effective treatment for this disease is canal repositioning procedures (CRP). Most patients return to normal after a single treatment. However, some patients still experience residual dizziness (RD) after treatment, and this disease's pathogenesis is currently unclear. The purpose of this study is to explore whether there are abnormal brain functional activities in patients with RD by using resting-state functional magnetic resonance imaging (rs-fMRI) and to provide imaging evidence for the study of the pathogenesis of RD. Materials and methods: The BPPV patients in the Second Affiliated Hospital of Xuzhou Medical University had been included from December 2021 to November 2022. All patients had been received the collection of demographic and clinical characteristics (age, gender, involved semicircular canal, affected side, CRP times, BPPV course, duration of RD symptoms, and whether they had hypertension, diabetes, coronary heart disease.), scale assessment, including Dizziness Handicap Inventory (DHI), Hamilton Anxiety Inventory (HAMA), Hamilton Depression Inventory (HAMD), rs-fMRI data collection, CRP treatment, and then a one-month follow-up. According to the follow-up results, 18 patients with RD were included. At the same time, we selected 19 healthy individuals from our hospital's physical examination center who matched their age, gender as health controls (HC). First, the amplitude of low-frequency fluctuations (ALFF) analysis method was used to compare the local functional activities of the two groups of subjects. Then, the brain regions with different ALFF results were extracted as seed points. Functional connectivity (FC) analysis method based on seed points was used to explore the whole brain FC of patients with RD. Finally, a correlation analysis between clinical features and rs-fMRI data was performed. Results: Compared to the HC, patients with RD showed lower ALFF value in the right precuneus and higher ALFF value in the right superior temporal gyrus (STG). When using the right STG as a seed point, it was found that the FC between the right STG, the right supramarginal gyrus (SMG), and the left precuneus was decreased in RD patients. However, no significant abnormalities in the FC were observed when using the right precuneus as a seed point. Conclusion: In patients with RD, the local functional activity of the right precuneus is weakened, and the local functional activity of the right STG is enhanced. Furthermore, the FC between the right STG, the right SMG, and the left precuneus is weakened. These changes may explain the symptoms of dizziness, floating sensation, walking instability, neck tightness, and other symptoms in patients with RD to a certain extent.

17.
Burns Trauma ; 11: tkad041, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849944

RESUMO

Background: Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N'-di-sec-butyl-N, N'- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. Methods: The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo. Results: Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO-, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO- could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both in vitro and in vivo. Conclusions: The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

18.
Hortic Res ; 10(4): uhad035, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37799627

RESUMO

Cold-induced sweetening (CIS), the undesirable sugar accumulation in cold-stored potato (Solanum tuberosum L.) tubers, is a severe postharvest issue in the potato processing industry. Although the process of sucrose hydrolysis by vacuolar invertase during potato CIS is well understood, there is limited knowledge about the transportation of sucrose from the cytosol to the vacuole during postharvest cold storage. Here, we report that among the three potato tonoplast sugar transporters (TSTs), StTST1 exhibits the highest expression in tubers during postharvest cold storage. Subcellular localization analysis demonstrates that StTST1 is a tonoplast-localized protein. StTST1 knockdown decreases reducing sugar accumulation in tubers during low-temperature storage. Compared to wild-type, potato chips produced from StTST1-silenced tubers displayed significantly lower acrylamide levels and lighter color after cold storage. Transcriptome analysis manifests that suppression of StTST1 promotes starch synthesis and inhibits starch degradation in cold-stored tubers. We further establish that the increased sucrose content in the StTST1-silenced tubers might cause a decrease in the ABA content, thereby inhibiting the ABA-signaling pathway. We demonstrate that the down-regulation of ß-amylase StBAM1 in StTST1-silenced tubers might be directly controlled by ABA-responsive element-binding proteins (AREBs). Altogether, we have shown that StTST1 plays a critical role in sugar accumulation and starch metabolism regulation during postharvest cold storage. Thus, our findings provide a new strategy to improve the frying quality of cold-stored tubers and reduce the acrylamide content in potato chips.

19.
Heliyon ; 9(9): e19919, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809877

RESUMO

Rice (Oryza sativa L.) is a staple food that feeds over half of the world's population, and the contents of metallic elements in rice grain play important roles in human nutrition. In this study, the contents of important metallic elements were determined by ICP-OES, and included cadmium (Cd), zinc (Zn), manganese (Mn), copper (Cu), iron (Fe), nickel (Ni), calcium (Ca), and magnesium (Mg) in brown rice, in the first node from the top (Node 1), in the second node from the top (Node 2), and in roots of 55 hybrids and their parental lines. The heritability of metallic element contents (MECs), the general combining ability (GCA) for MEC, and the correlation between MECs in different organs/tissues of hybrids were also analyzed. The results indicated that: (1) there was a positive correlation between the contents of Cd and Zn in nodes and roots, but a negative correlation between the contents of Cd and Zn in brown rice of the hybrids(2) the GCA for MECs can be used to evaluate the ability of the parental lines to improve the metal contents in brown rice of the hybrids(3) the contents of Cd, Zn, Ca, and Mg in brown rice were mainly affected by additive genetic effects(4) the restorer lines R2292 and R2265 can be used to cultivate hybrids with high Zn and low Cd contents in the brown rice.

20.
Anal Chem ; 95(37): 14101-14110, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37674256

RESUMO

Intracellular dynamic assembly of DNA structures may be beneficial for the development of multifunctional nanoplatforms for the regulation of cell behaviors, providing new strategies for disease diagnosis and intervention. Herein, we propose the dynamic assembly of DNA coacervates in living cells triggered by miRNA-21 and K+, which can be used for both miRNA imaging and mitochondrial intervention. The rationale is that miRNA-21 can trigger the hybridization chain reaction to generate G-quadruplex precursors, and K+ can mediate the assembly of G-quadruplex-based coacervates, allowing the colorimetric detection of miRNA-21 ranging from 10 pM to 10 µM. Moreover, the as-formed DNA coacervates can specifically target mitochondria in MCF-7 breast cancer cells using the MCF-7 cell membrane as delivery carriers, which further act as an anionic shielding to inhibit communication between mitochondria and environments, with a significant inhibitory effect on ATP production and cellular migration behaviors. This work provides an ideal multifunctional nanoplatform for rationally interfering with cellular metabolism and migration behaviors through the dynamic assembly of DNA coacervates mediated by endogenous molecules, which has a large number of potential applications in the biomedical field, especially theranostics for cancer metastasis.


Assuntos
DNA , MicroRNAs , Replicação do DNA , Diagnóstico por Imagem , MicroRNAs/genética , Mitocôndrias
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