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1.
iScience ; 27(4): 109424, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38510146

RESUMO

To meet the requirements of fast response and simple process of deep ultraviolet (UV) pulsed laser detector, table salt (TS) was used as laser detection material in combination with a variable resistor to achieve single-pulse laser detection. Under the irradiation of a KrF excimer laser, the laser-induced voltage (LIV) of TS was influenced by the dynamic process of laser-induced plasma, and the whole process was well fitted with the sum of the three exponential functions. As the applied bias voltage (Vb) and incident laser energy (Ein) increased, the LIV amplitude (Vp) increased and the response time decreased. When the variable resistor (R) was reduced to 14.7 Ω, the response time of LIV decreased from ∼300 µs to ∼20 ns, which is the same as the duration of laser pulse. This research provided a simple, low-cost, and fast method for the detection of UV single-pulse laser based on the laser-TS interaction.

2.
Int J Biol Macromol ; 264(Pt 2): 130690, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38458297

RESUMO

Nowadays, non-small cell lung cancer (NSCLC) is still one of the most life-threatening diseases in the world. In previous studies, a fungal protein PFAP with anti-NSCLC properties was isolated and identified from Pleurotus ferulae lanzi. In this study, the amino acid sequence of PFAP was analyzed and found to be highly homologous to the aegerolysin family. PFAP, like other members of the aegerolysin family, specifically recognizes lipid raft domains rich in cholesterol and sphingomyelin, which is probably its specific anti-tumor mechanism. Previous studies have shown that PFAP can induce AMPK-mediated autophagy and G1-phase cell cycle arrest in A549 lung cancer cells. This study further revealed that PFAP can also induce paraptosis and endoplasmic reticulum stress (ERS) in A549 cells in vitro by targeting AMPK. PFAP induces multi-pathway death of A549 cells, and thus demonstrates its potential value for developing new drugs for NSCLC.

3.
Front Physiol ; 15: 1295776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322612

RESUMO

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of whole-body vibration training (WBVT) in patients with stroke, specifically focusing on its effects on physical function, activities of daily living (ADL), and quality of life (QOL). Additionally, potential moderators influencing WBVT outcomes were explored. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library from inception to September 2022. Eligible studies were randomized controlled trials employing WBVT in patients with stroke. Two investigators independently extracted the data and calculated the standardized mean difference (SMD) using random-effect models. Results: Twenty-five studies involving 991 patients were included in this meta-analysis. WBVT demonstrated significant reductions in spasticity (SMD = -0.33, 95% CI = -0.61 to -0.06, p = 0.02), improvements in motor function (SMD = 0.39, 95% CI = 0.16 to 0.61, p < 0.01), and enhancements in balance function (SMD = 0.28, 95% CI = 0.09 to 0.47, p < 0.01) in patients with stroke. However, no significant effects were observed for gait (SMD = -0.23, 95% CI = -0.50 to 0.04, p = 0.10), ADL (SMD = -0.01, 95% CI = -0.46 to 0.44, p = 0.97), or QOL (SMD = 0.12, 95% CI = -0.30 to 0.53, p = 0.59). Subgroup analyses revealed that variable frequency vibration and side-alternating vibration exhibited significant efficacy in reducing spasticity and improving motor and balance functions, while fixed frequency vibration and vertical vibration did not yield significant therapeutic benefits in these domains. Conclusion: Our findings indicate that WBVT may serve as a viable adjunct therapy for stroke patients to alleviate spasticity and enhance motor and balance functions. Variable frequency and side-alternating vibration appear to be crucial factors influencing the therapeutic effects of WBVT on these dysfunctions. Nonetheless, WBVT did not show significant effects on gait, ADL, or QOL in stroke patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022384319).

4.
Mater Today Bio ; 25: 100975, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38322662

RESUMO

Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hydrogels to produce aEB/HBC composite hydrogels. The aEB/HBC composite hydrogels exhibited reversible temperature-sensitive phase transition behavior and a hybrid porous network. In vitro analysis showed that the aEB/HBC composite hydrogels exhibited better antimicrobial activity than the PBS control, aEBs or HBC hydrogels and promoted M0 to M2 polarization but not M1 to M2 macrophage repolarization in culture. The in vivo results showed that the aEB/HBC composite hydrogels accelerated cutaneous wound closure, re-epithelialization, ingrowth of new blood vessels, and collagen deposition and reduced the scar width during wound healing in diabetic mice over time. Macrophage phenotype analysis showed that the aEB/HBC composite hydrogels induce M2 macrophage reactions continually, upregulate M2-related mRNA and protein expression and downregulate M1-related mRNA and protein expression. Therefore, the aEB/HBC composite hydrogels have excellent antimicrobial activity, promote M2 macrophage polarization and accelerate the functional and structural healing of diabetic cutaneous wounds.

5.
Sensors (Basel) ; 24(3)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38339725

RESUMO

Visual Simultaneous Localization and Mapping (VSLAM) estimates the robot's pose in three-dimensional space by analyzing the depth variations of inter-frame feature points. Inter-frame feature point mismatches can lead to tracking failure, impacting the accuracy of the mobile robot's self-localization and mapping. This paper proposes a method for removing mismatches of image features in dynamic scenes in visual SLAM. First, the Grid-based Motion Statistics (GMS) method was introduced for fast coarse screening of mismatched image features. Second, an Adaptive Error Threshold RANSAC (ATRANSAC) method, determined by the internal matching rate, was proposed to improve the accuracy of removing mismatched image features in dynamic and static scenes. Third, the GMS-ATRANSAC method was tested for removing mismatched image features, and experimental results showed that GMS-ATRANSAC can remove mismatches of image features on moving objects. It achieved an average error reduction of 29.4% and 32.9% compared to RANSAC and GMS-RANSAC, with a corresponding reduction in error variance of 63.9% and 58.0%, respectively. The processing time was reduced by 78.3% and 38%, respectively. Finally, the effectiveness of inter-frame feature mismatch removal in the initialization thread of ORB-SLAM2 and the tracking thread of ORB-SLAM3 was verified for the proposed algorithm.

6.
Phys Rev Lett ; 132(5): 056101, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38364152

RESUMO

The slow transition from an out-of-equilibrium glass towards a supercooled liquid is a complex relaxation phenomenon. In this Letter, we study the correlation between mechanical relaxation and equilibration kinetics in a Pd_{20}Pt_{20}Cu_{20}Ni_{20}P_{20} high-entropy metallic glass. The evolution of stress relaxation with aging time was obtained with an unprecedented detail, allowing us to pinpoint new interesting features. The long structural relaxation towards equilibrium contains a wide distribution of activation energies, instead of being just associated to the ß relaxation as commonly accepted. The stress relaxation time can be correlated with the equilibration rate and we observe a decrease of microstructural heterogeneity which contrasts with an increase of dynamic heterogeneity. These results significantly enhance our insight of the interplay between relaxation dynamics and thermodynamics in metallic glasses.

7.
Front Neurol ; 15: 1332882, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405400

RESUMO

Background: Previous studies showed that vagus nerve stimulation (VNS) can improve cognitive function in patients with epilepsy, but there is still great controversy about the effect of VNS on cognitive function in patients with epilepsy. Objective: To investigate the effect of VNS on the cognitive function of epilepsy patients. Methods: Clinical trials published in PubMed, The Cochrane Library, and Embase before September 20, 2022, were comprehensively searched. Primary outcomes were overall cognitive performance, executive function, attention, memory; Secondary outcomes were seizure frequency, mood, and quality of life (QOL). Random effects were used to calculate the pooled outcome. Results: Twenty clinical trials were included. There was no significant improvement in overall cognitive performance in patients with epilepsy after VNS treatment (SMD = 0.07; 95% CI: -0.12 to 0.26; I2 = 0.00%) compared to pre-treatment. Compared to pre-treatment, there was no significant difference in executive function (SMD = -0.50; 95% CI: -1.50 to 0.50; p = 0.32), attention (SMD = -0.17; 95% CI: -0.43 to 0.09; p = 0.21) and memory (SMD = 0.64; 95% CI: -0.11 to 1.39; p = 0.09), but there were significant differences in seizure frequency, mood, and quality of life in patients with epilepsy after VNS. Conclusion: This meta-analysis did not establish that VNS can significantly improve cognitive function in patients with epilepsy, but it shows that VNS can significantly improve the seizure frequency, mood and quality of life of patients with epilepsy. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023384059.

8.
Mediators Inflamm ; 2024: 4121166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405620

RESUMO

The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3'-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis.


Assuntos
Benzofuranos , Depsídeos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , Animais , Camundongos , MicroRNAs/metabolismo , Músculo Liso Vascular , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Células Cultivadas , Inflamação/metabolismo , Glucose/toxicidade , Glucose/metabolismo , Proliferação de Células , Miócitos de Músculo Liso/metabolismo
9.
Hum Brain Mapp ; 45(2): e26575, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339909

RESUMO

Functional signals emerge from the structural network, supporting multiple cognitive processes through underlying molecular mechanism. The link between human brain structure and function is region-specific and hierarchical across the neocortex. However, the relationship between hierarchical structure-function decoupling and the manifestation of individual behavior and cognition, along with the significance of the functional systems involved, and the specific molecular mechanism underlying structure-function decoupling remain incompletely characterized. Here, we used the structural-decoupling index (SDI) to quantify the dependency of functional signals on the structural connectome using a significantly larger cohort of healthy subjects. Canonical correlation analysis (CCA) was utilized to assess the general multivariate correlation pattern between region-specific SDIs across the whole brain and multiple cognitive traits. Then, we predicted five composite cognitive scores resulting from multivariate analysis using SDIs in primary networks, association networks, and all networks, respectively. Finally, we explored the molecular mechanism related to SDI by investigating its genetic factors and relationship with neurotransmitter receptors/transporters. We demonstrated that structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. We revealed better performance in cognition prediction is achieved by using high-level hierarchical SDIs, with varying significance of different brain regions in predicting cognitive processes. We found that the SDIs were associated with the gene expression level of several receptor-related terms, and we also found the spatial distributions of four receptors/transporters significantly correlated with SDIs, namely D2, NET, MOR, and mGluR5, which play an important role in the flexibility of neuronal function. Collectively, our findings corroborate the association between hierarchical macroscale structure-function decoupling and individual cognition and provide implications for comprehending the molecular mechanism of structure-function decoupling. PRACTITIONER POINTS: Structure-function decoupling is hierarchical across the neocortex, spanning from primary networks to association networks. High-level hierarchical structure-function decoupling contributes much more than low-level decoupling to individual cognition. Structure-function decoupling could be regulated by genes associated with pivotal receptors that are crucial for neuronal function flexibility.


Assuntos
Conectoma , Neocórtex , Fenômenos Fisiológicos do Sistema Nervoso , Humanos , Imageamento por Ressonância Magnética/métodos , Cognição/fisiologia , Encéfalo/fisiologia , Conectoma/métodos , Neocórtex/diagnóstico por imagem
10.
Artigo em Inglês | MEDLINE | ID: mdl-38290467

RESUMO

Phenolic acids and their analogues in nature exist in many diseases of oxidative stress with beneficial effects on human health (such as cancer). Phenolic acids possess a variety of pharmacological activities, with anti-inflammatory, anticancer and cytotoxic, antioxidant, immunomodulatory, antimicrobial, insecticidal and other biological activities. Numerous in vitro and in vivo studies have shown that because phenolic acids have antioxidant capacity, they can reflect their strong anticancer potential by regulating cell growth and metastasis and promoting cancer cell death. Studies have shown that the consumption of natural polyphenols can significantly reduce the risk of cancer metastasis. A combination of phenolic acids with traditional chemoradiation or other polyphenols may be effective in reducing cancer spread.Ferulic acid is ubiquitous, and widely found in plants, such as angelica, chuanxiong, cohote, three, edge, reed root, tomato, sweet corn, and rice are produced by the metabolism of phenylalanine and tyrosine. It is the most abundant hydroxyl cassia bark-acid acid in the plant kingdom, with anti-inflammatory, antidiabetic, anticancer and antioxidant activity, and polyphenols composed of hydroxyl cassia bark-acid derivatives, flavone-3-alcohol and flavonol retain non-cancer-cells-and-significantly-inhibit glioblastoma viability in a dose-dependent manner, which deserves further investigation as potential anticancer drugs. This paper summarizes the role of ferulic acid in the PI3K / AKT pathway and its mechanism in glioblastoma resistance.

11.
Medicine (Baltimore) ; 103(4): e37013, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277577

RESUMO

RATIONALE: Sarcomatoid hepatocellular carcinoma (SHC) is an uncommon variant of hepatocellular carcinoma (HCC), characterized by HCC features combined with sarcomatoid histology and manifestations. The simultaneous occurrence of HCC and hepatosarcomatoid carcinoma is infrequent. This report presents a distinctive instance of HCC coexisting with hepatic sarcomatoid carcinoma in a 56-year-old male. The case exhibits an unusual clinical presentation, diagnosis, treatment, and prognosis. Through the presentation of this case, we aspire to contribute novel concepts to shape forthcoming strategies encompassing SHC diagnosis and treatment. PATIENT CONCERNS: The 56-year-old male patient was admitted to the hospital, due to discovering a hepatic mass lasting for over 2 months. DIAGNOSES: Ultimately, combined hepatocellular and SHC diagnosis was conclusively confirmed through histopathological and imaging examinations. INTERVENTION: In this case, our approach encompassed hepatectomy coupled with ultrasound-guided radiofrequency ablation for HCC. Intraoperative ultrasound localization was employed for accurate tumor identification, followed by postoperative hepatic artery embolization to facilitate meticulous tumor resection. OUTCOMES: He underwent hepatic arteriography chemoembolization treatment and is currently stable, experiencing regular chemotherapy follow-up visits. LESSONS: The presence of distinct tumor types concurrently can influence treatment choices and prognosis. Given the intricate nature of this condition, crafting an optimal treatment strategy necessitates the incorporation of variables such as the patient age, tumor characteristics, liver function, and other pertinent factors.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Hepatectomia/métodos , Prognóstico
12.
Value Health ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38244982

RESUMO

OBJECTIVES: China Health-Related Outcomes Measures (CHROME) was an initiative aimed at developing a system of preference-based health-related quality of life instruments for China. CHROME-cardiovascular disease (CVD) is a CVD-specific instrument with 14 items developed under this initiative. This study aimed to test the psychometric properties of CHROME-CVD. METHODS: This validation study was conducted using cross-sectional questionnaire survey in China. Eligible patients with CVD were recruited and asked to complete the CHROME-CVD, the EQ-5D-5L, and a CVD-specific nonpreference-based health-related quality of life instrument selected according to the confirmed diagnosis of the patients. Item evaluation, internal consistency, measurement invariance, test-retest reliability, structural validity, and construct validity were tested using classic test theory. Item response theory was used to evaluate item-level performance. RESULTS: A total of 444 patients with CVD (coronary artery disease, n = 276, heart failure, n = 104, angina, n = 33, and atrial fibrillation, n = 16) from 6 provinces in China were enrolled for the validation. Exploratory factor analysis identified 4 factors: chest pain, other symptoms, physical health, and mental and social health. Cronbach's alpha and intraclass correlation coefficient were >0.8. A total of 20 of 26 (76.9%), and 90 of 95 (94.7%) predefined hypotheses were met for convergent and discriminant validities, respectively. No important difference was identified between subgroups of gender and residency. Response options of 10 items were found overlapped based on categorical response curves, which led to modification to 4-level response options. Wording of 3 items were modified by referring wordings of reference instruments. CONCLUSION: The validation of the CHROME-CVD demonstrated generally good psychometric properties. Further validation on the modified CHROME-CVD is needed.

13.
Acta Psychol (Amst) ; 243: 104154, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266579

RESUMO

Much of the previous research has used experimental studies to explore the positive predictive effect of nostalgia on life satisfaction. However, the possible mediating effects involved remain unclear. To analyze the chain mediating mechanism between perceived social support and meaning in life in the relationship between nostalgia and life satisfaction and to improve the positive application of nostalgia to life satisfaction to ensure the physical and mental health of individuals, this study adopted the method of questionnaire survey, applied the Southampton Nostalgia scale, Perceived Social Support scale, Meaning in Life Scale and Life Satisfaction Scale. This study conducted a horizontal survey on 452 subjects recruited online from Gansu Province, Guangdong Province, Qinghai Province, and other places in China. The results showed that (1) there was a significant positive correlation between nostalgia and perceived social support, presence of meaning in life, searching for meaning in life, and life satisfaction. (2) Perceived social support and meaning in life play a chain mediating role in the relationship between nostalgia and life satisfaction. (3) Perceived social support and different dimensions of meaning in life are different in the relationship between nostalgia and life satisfaction. The findings contribute to understanding the chain-mediated mechanism between life satisfaction and nostalgia and provide recommendations for psychological service providers to apply nostalgia to enhance individual life satisfaction.


Assuntos
Satisfação Pessoal , Apoio Social , Humanos , Inquéritos e Questionários , China
14.
Biomol Biomed ; 2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38190139

RESUMO

Vascular calcification (VC) is a critical complication in chronic kidney disease (CKD), where transcription factors (TFs) and microRNAs (miRs) could potentially play a pivotal role in its pathogenesis and progression. To explore the potential molecular mechanism by which the TF D-box-binding protein (DBP) regulates the miR-195-5p/cyclin D1 (CCND1) axis and its impact on aortic VC in CKD rats, we established a rat model of CKD with VC through a 5/6 nephrectomy procedure. This model was treated with lentivirus overexpressing DBP or CCND1 to analyze their roles in aortic VC. Additionally, an in vitro cell model of VC was induced by high phosphorus. This model underwent transfection with lentivirus overexpressing DBP or miR-195-5p mimic/inhibitor to confirm their regulatory roles in aortic VC in vitro. We assessed the interactions between DBP and miR-195-5p, as well as between miR-195-5p and CCND1. Our results indicated that the expression of DBP and miR-195-5p was reduced, while CCND1 levels were elevated in both the rat and cell models.  Overexpression of miR-195-5p inhibited VC in vascular smooth muscle cells (VSMCs). Bioinformatics prediction and dual luciferase assays confirmed that DBP could act as a TF to enhance miR-195-5p expression, with Ccnd1 identified as a downstream target gene of miR-195-5p. Overexpression of DBP inhibited aortic calcification in CKD rats, whereas overexpression of CCND1 produced the opposite effect. In conclusion, the TF DBP can inhibit CCND1 expression through transcriptional activation of miR-195-5p, thereby preventing VC in rats with CKD.

15.
Open Med (Wars) ; 19(1): 20230883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38205152

RESUMO

Kashin-Beck disease (KBD) is an endemic osteochondropathy. A specific gene called SRY-box transcription factor 6 (SOX6) is important for forming cartilage. This study aims to explore the potential correlation between SOX6 single nucleotide polymorphisms (SNPs) and KBD risk for the first time. In the case-control study, 735 unrelated Chinese Han individuals were enrolled. The four mutation sites of the SOX6 gene (rs4539287 G/A, rs3203295 C/A, rs7928675 C/A, and rs10832681 A/G) were screened and genotyped on the Agena MassARRAY platform. The correlation between SOX6 SNPs and KBD risk was explored based on logistic regression analysis. The interaction between SNP and SNP was analyzed based on the multi-factor dimensionality reduction (MDR) method. Overall analysis revealed a remarkable correlation between rs7928675 and rs10832681 and the reduction of KBD risk (p < 0.05). Subgroup analyses further indicated that these two SNPs have a significant protective effect on KBD risk among participants aged ≤65 years, males, and non-smokers (p < 0.05). MDR displayed a marked interaction between rs3203295 and rs10832681. Our study revealed that SOX6 rs7928675 and rs10832681 are markedly correlated with a reduced risk of KBD in the Chinese Han population, providing a new direction for the prevention, diagnosis, and treatment of KBD.

16.
Sci Adv ; 10(4): eadd9485, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38266097

RESUMO

Type IV pili (TFP) are known to be functionally related to cell motilities and natural transformation in many bacteria. However, the molecular and ecological functions of the TFP have rarely been reported for photosynthetic cyanobacteria. Here, by labeling pili in model cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942), we have quantitatively characterized the TFP and its driven twitching motility in situ at the single-cell level. We found an oscillating pattern of TFP in accordance with the light and dark periods during light-dark cycles, which is correlated positively to the oscillating pattern of the natural transformation efficiency. We further showed that the internal circadian clock plays an important role in regulating the oscillating pattern of TFP, which is also supported by evidences at the molecular level by tracking the expression of 16 TFP-related genes. This study adds a detailed picture toward the gap between TFP and its relations to circadian regulations in Syn7942.


Assuntos
Relógios Circadianos , Synechococcus , Synechococcus/genética , Fímbrias Bacterianas , Cabelo
17.
ACS Nano ; 18(3): 2261-2278, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38207332

RESUMO

Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsis-associated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ, yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the "superbug" MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.


Assuntos
Lipossomos , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Receptores de Antígenos Quiméricos , Sepse , Infecções Estafilocócicas , Animais , Camundongos , Receptores de Antígenos Quiméricos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , RNA Mensageiro , Antibacterianos/farmacologia , Macrófagos , Sepse/tratamento farmacológico , Lipídeos/farmacologia
18.
World J Gastrointest Oncol ; 16(1): 244-250, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38292849

RESUMO

BACKGROUND: Schwannomas are uncommon tumors originating from Schwann cells, forming the neural sheath. They account for approximately 2%-6% of all mesenchymal tumors and are most commonly identified in peripheral nerve trunks, with rarity in the gastrointestinal tract. Among gastrointestinal locations, the stomach harbors the majority of nerve sheath tumors, while such occurrences in the sigmoid colon are exceptionally infrequent. CASE SUMMARY: This study presented a clinical case involving a 60-year-old female patient who, during colonoscopy, was diagnosed with a submucosal lesion that was later identified as a nerve sheath tumor. The patient underwent surgical resection, and the diagnosis was confirmed through immunohistochemistry. This study highlighted an exceptionally uncommon occurrence of a nerve sheath tumor in the sigmoid colon, which was effectively managed within our department. Additionally, a comprehensive review of relevant studies was conducted. CONCLUSION: The preoperative diagnosis of nerve sheath tumors poses challenges, as the definitive diagnosis still relies on pathology and immunohistochemistry. Although categorized as benign, these tumors have the potential to demonstrate malignant behavior. Consequently, the optimal treatment approach entails the complete surgical excision of the tumor, ensuring the absence of residual lesions at the margins.

19.
JAMA Cardiol ; 9(3): 233-242, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38198131

RESUMO

Importance: The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. Objective: To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. Design, Setting, and Participants: This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. Exposures: CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. Main Outcomes and Measures: The main outcome was first incident CHD. Results: Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. Conclusions: This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/epidemiologia , Hematopoiese Clonal , Estudos de Coortes , Estudos Prospectivos , Células Germinativas
20.
Anticancer Drugs ; 35(1): 1-11, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37104099

RESUMO

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular chloride channel 1 (CLIC1) expression was increased in AGS/DDP and MKN28/DDP, and as compared to the parental cells, autophagy was activated. In addition, the sensitivity of gastric cancer cells to DDP was decreased compared to the control group, and autophagy increased after overexpression of CLIC1. On the contrary, gastric cancer cells were more sensitive to cisplatin after transfection of CLIC1siRNA or treatment with autophagy inhibitors. These experiments suggest that CLIC1 could alter the sensitivity of gastric cancer cells to DDP by activating autophagy. Overall, the results of this study recommend a novel mechanism of DDP resistance in gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Autofagia , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Canais de Cloreto/genética , Canais de Cloreto/farmacologia , Canais de Cloreto/uso terapêutico
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