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2.
Mol Carcinog ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860593

RESUMO

Mixed phenotype acute leukemia (MPAL) is a type of acute leukemia in which encompasses mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. Philadelphia chromosome-positive (Ph+) MPAL is a rare subgroup with a poor prognosis and accounts for <1% of adult acute leukemia. Until now, there is still no consensus on how to best treat Ph+ MPAL. Here, we report a 62-year-old male with Ph+ (atypical e13a2 BCR-ABL1 fusion protein) MPAL. This patient presented with recurrent and intense bone pain due to bone marrow necrosis (BMN). Besides, he did not achieve a complete remission for the first two chemotherapies, until he received flumatinib combined with hyper-CVAD (B) (a dose-intensive regimen include methotrexate and cytarabine). To our knowledge, this is the first report to describe the coexistence of BMN and atypical e13a2 BCR-ABL1 transcripts in patients with MPAL. This finding will bring new understandings in the diagnosis and treatment of Ph+ MPAL.

3.
Int Urol Nephrol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865001

RESUMO

PURPOSE: This study investigates the prognostic value of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) measured by chest CT in relation to all-cause and cardiovascular disease (CVD) mortality among hemodialysis (HD) patients. METHODS: A retrospective study was conducted from January 2015 to December 2021 involving HD patients at a dialysis center. Chest CT scans at the twelfth thoracic vertebra level (T12) were analyzed to assess SMI and SMD. Sex-specific cut-off values for two metrics were determined using maximally selected rank statistics. Hazard ratios (HRs) were calculated to evaluate the associations of SMI and SMD with mortality. The discrimination of prognostic models was also compared. RESULTS: The study included 603 patients with a median age of 58 years. Of these, 187 (31.0%) patients with SMI < 30.00 cm2/m2 (male) or < 25.04 cm2/m2 (female) and 192 (31.8%) patients with SMD < 32.25 HU (male) or < 30.64 HU (female) were categorized as lower SMI and SMD, respectively. Over a median follow-up of 3.8 years, 144 deaths occurred. Multivariate Cox regression analysis showed that lower SMI and SMD were independently associated with all-cause mortality (SMI: HR = 1.47, 95% CI 1.03-2.10; SMD: HR = 1.75, 95% CI 1.20-2.54) and CVD mortality (SMI: HR = 1.74, 95% CI 1.03-2.94; SMD: HR = 1.72, 95% CI 1.02-2.95). Adding SMI and SMD to the established risk model improved the C-index from 0.82 to 0.87 (P < 0.001). Decision curve analysis showed that the prognostic model incorporating both SMI and SMD offered the highest net benefit for predicting all-cause mortality. CONCLUSIONS: Muscle metrics derived from CT scans at T12 level provide valuable prognostic information which could enhance the role of chest CT in muscle assessment among HD patients.

4.
J Neurol ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869825

RESUMO

Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and cardiac dysfunction, collectively termed stroke-heart syndrome (SHS). These cardiac alterations typically peak within 72 h of stroke onset and can have long-term effects on cardiac function. Post-stroke cardiac complications seriously affect prognosis and are the second most frequent cause of death in patients with stroke. Although traditional vascular risk factors contribute to SHS, other potential mechanisms indirectly induced by stroke have also been recognized. Accumulating clinical and experimental evidence has emphasized the role of central autonomic network disorders and inflammation as key pathophysiological mechanisms of SHS. Therefore, an assessment of post-stroke cardiac dysautonomia is necessary. Currently, the development of treatment strategies for SHS is a vital but challenging task. Identifying potential key mediators and signaling pathways of SHS is essential for developing therapeutic targets. Therapies targeting pathophysiological mechanisms may be promising. Remote ischemic conditioning exerts protective effects through humoral, nerve, and immune-inflammatory regulatory mechanisms, potentially preventing the development of SHS. In the future, well-designed trials are required to verify its clinical efficacy. This comprehensive review provides valuable insights for future research.

5.
J Cell Mol Med ; 28(11): e18370, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38818568

RESUMO

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.


Assuntos
Biologia Computacional , MicroRNAs , Neutrófilos , Proteínas Proto-Oncogênicas c-fos , Tromboembolia Venosa , Humanos , MicroRNAs/genética , MicroRNAs/sangue , MicroRNAs/metabolismo , Neutrófilos/metabolismo , Tromboembolia Venosa/genética , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/sangue , Biologia Computacional/métodos , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Regulação da Expressão Gênica , Masculino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Feminino , Biomarcadores/sangue , Biomarcadores/metabolismo
6.
Int J Food Microbiol ; 419: 110747, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38772218

RESUMO

Campylobacter jejuni is recognized as a significant foodborne pathogen, and recent studies have indicated a rising trend of aminoglycosides resistance gene aph(2″)-If among C. jejuni isolates from food-producing animals in China. However, systematic information about aph(2″)-If-positive C. jejuni from food-producing animals and other sources worldwide based on whole-genome analysis remains a knowledge gap. In this study, we aimed to analyze the worldwide distribution, genetic environment and phylogenetic tree of aph(2″)-If by utilizing Whole Genome Sequencing (WGS) data obtained, coupled with information in the GenBank database. A total of 160C. jejuni isolates in the GenBank database and 14C. jejuni isolates in our laboratory carrying aph(2″)-If gene were performed for further analysis. WGS analysis revealed the global distribution of aph(2″)-If among C. jejuni from 6 countries. Multilocus Sequence Typing(MLST) results indicated that 70 STs were involved in the dissemination of aph(2″)-If, with ST10086 being the predominant ST. Whole-genome Multilocus Sequence Typing(wg-MLST) analysis according to times, countries, and origins of C. jejuni isolation further demonstrated a close relationship between aph(2″)-If carrying C. jejuni isolates from farm and food. The findings also revealed the existence of 32 distinct types of genetic environments surrounding aph(2″)-If among these isolates. Notably, Type 30, characterized by the arrangement ISsag10-deoD-ant(9)-hp-hp-aph(2″)-If, emerged as the predominant genetic environment. In conclusion, our analysis provides the inaugural perspective on the worldwide distribution of aph(2″)-If. This resistance gene demonstrates horizontal transferability and regional diffusion in a clonal pattern. The close association observed among aph(2″)-If-positive C. jejuni strains isolated from poultry, food, and clinical environments underscores the potential for zoonotic transmission from these isolates.


Assuntos
Aminoglicosídeos , Antibacterianos , Infecções por Campylobacter , Campylobacter jejuni , Farmacorresistência Bacteriana , Tipagem de Sequências Multilocus , Filogenia , Campylobacter jejuni/genética , Campylobacter jejuni/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Aminoglicosídeos/farmacologia , Animais , Antibacterianos/farmacologia , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/veterinária , Infecções por Campylobacter/epidemiologia , Sequenciamento Completo do Genoma , Humanos , Prevalência , China , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana
7.
Dalton Trans ; 53(20): 8750-8755, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712563

RESUMO

Direct ethanol fuel cells (DEFCs), which have been widely recognized as nontoxic and green energy conversion devices, show attractive application prospects for liquid hydrogen-carriers, due to the higher specific energy and lower toxicity of ethanol. Pt-based catalysts are widely used in DEFCs, while their poor poisoning resistance highlights the importance of composition and structure optimization. Herein, we synthesized a series of reduced graphene oxide supported ternary alloy AuxPt1-xCu3/rGO (x = 0-1) catalysts with excellent ethanol oxidation performance and a composition-dependent volcano plot trend of the ordering degree was observed and rationalized. The highest Pt-normalized mass activity of Au0.8Pt0.2Cu3/rGO is attributed to the optimized CO binding energy according to DFT calculations. This work not only provides an efficient EOR catalyst based on ordered alloys AuxPt1-xCu3 (x = 0-1), but also offers valuable insight into the role of a third metal in tuning the structure and function of alloys.

8.
Aging Dis ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38739941

RESUMO

Our study aimed to construct a predictive model for identifying instances of futile recanalization in patients with anterior circulation occlusion acute ischemic stroke (AIS) who achieved complete reperfusion following endovascular therapy. We included 173 AIS patients who attained complete reperfusion, as indicated by a Modified Thrombolysis in Cerebral Infarction (mTICI) scale score of 3. Our approach involved a thorough analysis of clinical factors, imaging biomarkers, and potential no-reflow biomarkers through both univariate and multivariate analyses to identify predictors of futile recanalization. The comprehensive model includes clinical factors such as age, presence of diabetes, admission NIHSS score, and the number of stent retriever passes; imaging biomarkers like poor collaterals; and potential no-reflow biomarkers, notably disrupted blood-brain barrier (OR 4.321, 95% CI 1.794-10.405; p = 0.001), neutrophil-to-lymphocyte ratio (NLR; OR 1.095, 95% CI 1.009-1.188; p = 0.030), and D-dimer (OR 1.134, 95% CI 1.017-1.266; p = 0.024). The model demonstrated high predictive accuracy, with a C-index of 0.901 (95% CI 0.855-0.947) and 0.911 (95% CI 0.863-0.954) in the original and bootstrapping validation samples, respectively. Notably, the comprehensive model showed significantly improved predictive performance over models that did not include no-reflow biomarkers, evidenced by an integrated discrimination improvement of 8.86% (95% CI 4.34%-13.39%; p < 0.001) and a categorized reclassification improvement of 18.38% (95% CI 3.53%-33.23%; p = 0.015). This model, which leverages the potential of no-reflow biomarkers, could be especially beneficial in healthcare settings with limited resources. It provides a valuable tool for predicting futile recanalization, thereby informing clinical decision-making. Future research could explore further refinements to this model and its application in diverse clinical settings.

9.
J Bone Miner Res ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722812

RESUMO

Skeletal growth, modeling and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In the present study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1. To assess the in vivo relevance of this regulation, we crossed Omd-deficient mice with a mouse line harboring an inducible, osteoblast-specific Wnt1 transgene. After induction of Wnt1 expression for 1 or 3 weeks, the osteoanabolic potency of WNT1 was not impaired despite the Omd deficiency. Since current knowledge regarding the in vivo physiological function of OMD is limited, we next focused on skeletal phenotyping of wild-type and Omd-deficient littermates, in the absence of a Wnt1 transgene. Here we did not observe an impact of Omd deficiency on trabecular bone parameters by histomorphometry and µCT either. Importantly, however, male and female Omd-deficient mice at the ages of 12 and 24 weeks displayed a slender bone phenotype with significantly smaller long bones in the transversal dimension, while the longitudinal bone growth remained unaffected. Although mechanical testing revealed no significant changes explained by impaired bone material properties, atomic force microscopy of the femoral bone surface of Omd-deficient mice revealed moderate changes at the nanostructural level, indicating altered regulation of collagen fibril formation and aggregation. Taken together, our data demonstrate that, although OMD is dispensable for the osteoanabolic effect of WNT1, its deficiency in mice specifically modulates transversal cortical bone morphology.


We explored the physiological relevance of the protein Osteomodulin (OMD) that we previously found to be induced by the osteoanabolic molecule WNT1. While other studies have shown that OMD is involved in the regulation of collagen fibril formation in vitro, its function in vivo has not been investigated. We confirmed that OMD is directly regulated by WNT1 but surprisingly, when we bred mice lacking OMD with mice engineered to highly express WNT1, we found that the osteoanabolic effect of WNT1 was unaffected by the absence of OMD. Interestingly, mice lacking OMD did show differences in the shape of their bones, particularly in their width, despite no significant changes in bone density or length. Investigation of the bone matrix of mice lacking OMD at the nanostructural level indicated moderate differences in the organization of collagen fibrils. This study provided further insights into the effect of WNT1 on bone metabolism and highlighted a specific function of OMD in skeletal morphology.

10.
JAMA Neurol ; 81(6): 594-602, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648030

RESUMO

Importance: Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. Objective: To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Intervention: Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. Main Outcome: The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. Results: A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). Conclusions and Relevance: In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. Trial Registration: ClinicalTrials.gov Identifier: NCT04491695.


Assuntos
Aspirina , AVC Isquêmico , Inibidores da Agregação Plaquetária , Tirofibana , Humanos , Tirofibana/administração & dosagem , Tirofibana/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais
11.
Front Aging Neurosci ; 16: 1384075, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596595

RESUMO

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.

12.
Front Microbiol ; 15: 1362479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572237

RESUMO

Driven by the good developmental potential and favorable environment at this stage, Ganoderma lucidum is recognized as a precious large fungus with medicinal and nutritional health care values. Among them, polysaccharides, triterpenoids, oligosaccharides, trace elements, etc. are important bioactive components in G. lucidum. These bioactive components will have an impact on gut flora, thus alleviating diseases such as hyperglycemia, hyperlipidemia and obesity caused by gut flora disorder. While numerous studies have demonstrated the ability of G. lucidum and its active components to regulate gut flora, a systematic review of this mechanism is currently lacking. The purpose of this paper is to summarize the regulatory effects of G. lucidum and its active components on gut flora in cardiovascular, gastrointestinal and renal metabolic diseases, and summarize the research progress of G. lucidum active components in improving related diseases by regulating gut flora. Additionally, review delves into the principle by which G. lucidum and its active components can treat or assist treat diseases by regulating gut flora. The research progress of G. lucidum in intestinal tract and its potential in medicine, health food and clinical application were fully explored for researchers.

13.
Brain Circ ; 10(1): 77-84, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655440

RESUMO

PURPOSE: In patients undergoing endovascular thrombectomy (EVT) with acute ischemic stroke (AIS), dynamic cerebral autoregulation (dCA) may minimize neurological injury from blood pressure fluctuations. This study set out to investigate the function of dCA in predicting clinical outcomes following EVT. METHODS: 43 AIS of the middle cerebral or internal carotid artery patients underwent with EVT, and 43 healthy individuals (controls) were enrolled in this case control research. The dCA was evaluated using transcranial Doppler 12 h and five days after EVT. The transfer function analysis was used to derive the dCA parameters, such as phase, gain, and coherence. The modified Rankin scale (mRS) at 3 months after EVT was used to assess the clinical outcomes. Thefavorable outcome group was defined with mRS ≤2 and the unfavorable outcome group was defined with mRS score of 3-6. Logistic regression analysis was performed to determine the risk factors of clinical outcomes. RESULTS: A significant impairment in dCA was observed on the ipsilateral side after EVT, particularly in patients with unfavorable outcomes. After 5 days, the ipsilateral phase was associated with poor functional outcomes (adjusted odds ratio [OR] = 0.911, 95% confidence interval [CI]: 0.854-0.972; P = 0.005) and the area under the curve (AUC) (AUC, 0.878, [95% CI: 0.756-1.000] P < 0.001) (optimal cutoff, 35.0°). Phase change was an independent predictor of clinical outcomes from 12 h to 5 days after EVT (adjusted OR = 1.061, 95% CI: 1.016-1.109, P = 0.008). CONCLUSIONS: dCA is impaired in patients with AIS after EVT. Change in dCA could be an independent factor related to the clinical outcomes.

14.
J Chem Phys ; 160(14)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38591682

RESUMO

Designing homogeneous networks is considered one typical strategy for solving the problem of strength and toughness conflict of polymer network materials. Experimentalists have proposed the hypothesis of obtaining a structurally homogeneous hydrogel by crosslinking tetra-armed polymers, whose homogeneity was claimed to be verified by scattering characterization and other methods. Nevertheless, it is highly desirable to further evaluate this issue from other perspectives. In this study, a coarse-grained molecular dynamics simulation coupled with a stochastic reaction model is applied to reveal the topological structure of a polymer network synthesized by tetra-armed monomers as precursors. Two different scenarios, distinguished by whether internal cross-linking is allowed, are considered. We introduce the Dijkstra algorithm from graph theory to precisely characterize the network structure. The microscopic features of the network structure, e.g., loop size, dispersity, and size distribution, are obtained via the Dijkstra algorithm. By comparing the two reaction scenarios, Scenario II exhibits an overall more idealized structure. Our results demonstrate the feasibility of the Dijkstra algorithm for precisely characterizing the polymer network structure. We expect this work will provide a new insight for the evaluation and description of gel networks and further help to reveal the dynamic process of network formation.

15.
J Intell ; 12(4)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38667711

RESUMO

Making judgments of learning (JOLs) can reactively alter memory itself, a phenomenon termed the reactivity effect. The current study recorded electroencephalography (EEG) signals during the encoding phase of a word list learning task to explore the neurocognitive features associated with JOL reactivity. The behavioral results show that making JOLs reactively enhances recognition performance. The EEG results reveal that, compared with not making JOLs, making JOLs increases P200 and LPC amplitudes and decreases alpha and beta power. Additionally, the signals of event-related potentials (ERPs) and event-related desynchronizations (ERDs) partially mediate the reactivity effect. These findings support the enhanced learning engagement theory and the elaborative processing explanation to account for the JOL reactivity effect.

16.
Cancer Lett ; 590: 216844, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38582394

RESUMO

Proper protein folding relies on the assistance of molecular chaperones post-translation. Dysfunctions in chaperones can cause diseases associated with protein misfolding, including cancer. While previous studies have identified CCT2 as a chaperone subunit and an autophagy receptor, its specific involvement in glioblastoma remains unknown. Here, we identified CCT2 promote glioblastoma progression. Using approaches of coimmunoprecipitation, mass spectrometry and surface plasmon resonance, we found CCT2 directly bound to KRAS leading to increased stability and upregulated downstream signaling of KRAS. Interestingly, we found that dihydroartemisinin, a derivative of artemisinin, exhibited therapeutic effects in a glioblastoma animal model. We further demonstrated direct binding between dihydroartemisinin and CCT2. Treatment with dihydroartemisinin resulted in decreased KRAS expression and downstream signaling. Highlighting the significance of CCT2, CCT2 overexpression rescued the inhibitory effect of dihydroartemisinin on glioblastoma. In conclusion, the study demonstrates that CCT2 promotes glioblastoma progression by directly binding to and enhancing the stability of the KRAS protein. Additionally, dihydroartemisinin inhibits glioblastoma by targeting the CCT2 and the following KRAS signaling. Our findings overcome the challenge posed by the undruggable nature of KRAS and offer potential therapeutic strategies for glioblastoma treatment.


Assuntos
Chaperonina com TCP-1 , Glioblastoma , Estabilidade Proteica , Proteínas Proto-Oncogênicas p21(ras) , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Animais , Chaperonina com TCP-1/metabolismo , Chaperonina com TCP-1/genética , Linhagem Celular Tumoral , Estabilidade Proteica/efeitos dos fármacos , Artemisininas/farmacologia , Progressão da Doença , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
17.
J Neurosci Res ; 102(3): e25324, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38515341

RESUMO

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.


Assuntos
Arteriosclerose Intracraniana , AVC Isquêmico , Adulto , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapia , Isquemia , Hemodinâmica , Glucose
18.
CNS Neurosci Ther ; 30(3): e14588, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38475869

RESUMO

AIMS: With the progress of thrombectomy technology, the vascular recanalization rate of patients with stroke has been continuously improved, but the proportion of futile recanalization (FR) is still quite a few. The long-term prognosis and survival of patients with FR and its influencing factors remain unclear. METHODS: Consecutive patients who received endovascular treatment (EVT) for ischemic stroke were enrolled between 2013 and 2021 from a single-center prospectively registry study. We evaluated the long-term outcome of these patients by Kaplan-Meier survival analysis, and the multivariable logistic regression curve was performed to analyze influencing factors. RESULTS: Among 458 patients with FR, 56.4% of patients survived at 1 year, and 50.4% at 2 years. In the multivariate regression analysis, age, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), posterior circulation infarct, general anesthesia, symptomatic intracerebral hemorrhage (sICH), and decompressive craniectomy were found to be related to unfavorable outcomes in long-term. Age, premorbid mRS, NIHSS, general anesthesia, and sICH were predictors of long-term mortality. CONCLUSIONS: Futile recanalization accounts for a large proportion of stroke patients after thrombectomy. This study on the long-term prognosis of such patients is beneficial to the formulation of treatment plans and the prediction of therapeutic effects.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Resultado do Tratamento , Acidente Vascular Cerebral/terapia , Prognóstico , Trombectomia , Hemorragia Cerebral/etiologia , Reperfusão , Isquemia Encefálica/terapia , Estudos Retrospectivos
19.
Clin Oral Investig ; 28(3): 206, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459220

RESUMO

OBJECTIVES: This finite element study aimed to simulate maxillary canine movement during anterior teeth retraction. MATERIALS AND METHODS: Three methods of maxillary canine movement including miniscrew sliding with high hooks (MSH), miniscrew sliding with low hooks (MSL), and the traditional sliding method (TS) without using miniscrews were simulated using three-dimensional finite element analysis. The initial displacement of the maxillary canine, the maximum principal stress of the periodontal ligament and the Von Mises stress were calculated. RESULTS: The distolingual tipping movements of the canine were shown in three movement modes. MSH showed a small tendency to lingual tipping movement and a extrusion movement while MSL had the largest lingual inclination. TS demonstrated a tendency toward distolingual torsion displacement. Compressive stress values were mainly concentrated in the range - 0.003 to -0.006 MPa. For tensile stress, the distribution of MSH and MSL was concentrated in the range 0.005 to 0.009 MPa, TS was mainly distributed about 0.003 MPa. Von Mises equivalent stress distribution showed no significant difference. CONCLUSIONS: The loss of tooth torque was inevitable, irrespective of which method was used to close the extraction space. However, miniscrew application and higher hooks reduced the loss of torque and avoided lingual rotation. CLINICAL RELEVANCE: This study shows that miniscrew implants with different hooks can better control the movement of the maxillary canines. The non-invasive nature of the finite element analysis and its good simulation of dental stress and instantaneous motion trend have a clinical advantage in the analysis of tooth movement.


Assuntos
Dente Canino , Técnicas de Movimentação Dentária , Dente Pré-Molar , Estresse Mecânico , Análise de Elementos Finitos , Torque , Técnicas de Movimentação Dentária/métodos , Maxila
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