Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 196
Filtrar
1.
J Control Release ; 373: 128-144, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38977134

RESUMO

In recent decades, there has been a burgeoning interest in cell membrane coating strategies as innovative approach for targeted delivery systems in biomedical applications. Platelet membrane-coated nanoparticles (PNPs), in particular, are gaining interest as a new route for targeted therapy due to their advantages over conventional drug therapies. Their stepwise approach blends the capabilities of the natural platelet membrane (PM) with the adaptable nature of manufactured nanomaterials, resulting in a synergistic combination that enhances drug delivery and enables the development of innovative therapeutics. In this context, we present an overview of the latest advancements in designing PNPs with various structures tailored for precise drug delivery. Initially, we describe the types, preparation methods, delivery mechanisms, and specific advantages of PNPs. Next, we focus on three critical applications of PNPs in diseases: vascular disease therapy, cancer treatment, and management of infectious diseases. This review presents our knowledge of PNPs, summarizes their advancements in targeted therapies and discusses the promising potential for clinical translation of PNPs.

3.
Front Neurol ; 15: 1411669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915797

RESUMO

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious. Aims: This study evaluates DAPT's effectiveness and safety for these patients. Methods: This review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4. Results: Analysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46-0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30-0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97-1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17-1.31, p = 0.15). Conclusion: DAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.

4.
Discov Oncol ; 15(1): 234, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896161

RESUMO

BACKGROUND: Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress. METHOD: CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C-C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP. CONCLUSION: ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment.

5.
Ann Anat ; 255: 152293, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823492

RESUMO

Ventricular septal defects (VSD) with outflow tract (OFT) malalignment are a common group of congenital heart diseases with varying severity. The developmental process of these defects is challenging to understand due to the complex nature of cardiac morphogenesis and the difficulties in visualizing the temporal and spatial changes that occur during pathogenesis. However, recent advancements in imaging techniques, such as high-resolution episcopic microscopy, have provided valuable insights into the normal septation of ventricular chambers and OFT alignment. Building upon this knowledge, we have utilized lightsheet microscopy, another innovative imaging method, to further investigate the developmental processes that lead to abnormal formation of the ventricular septum and the malalignment of arterial roots with the ventricular chambers. Our study highlights endocardial cushion hypoplasia and insufficient rotation of the outflow tract as two interrelated central factors contributing to the pathogenesis of these defects. This finding has the potential to enhance our understanding of the etiology of congenital heart diseases and may contribute to the development of improved diagnostic and therapeutic strategies in the future.

6.
Environ Sci Pollut Res Int ; 31(25): 37705-37716, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38780846

RESUMO

The hydrographic and environmental factors along the Three Gorges Reservoir (TGR) have been significantly altered since the Three Gorges Dam (TGD) began working in 2006. Here, we collected 54 water samples, and then measured the environmental factors, followed by sequencing of the 18S rRNA gene and subsequent analysis of community assembly mechanisms. The findings indicated that the majority of environmental variables (such as AN, TP, Chl-a, CODMn, and Cu) exhibited both temporal and spatial variations due to the influences of the TGD. The distribution of different environmental factors and microeukaryotic plankton communities is influenced by the changing seasons. The community structure in TGR showed variations across three seasons, possibly due to variations in their environmental preferences, inherent dissimilarities, and seasonal succession. Furthermore, different communities exhibited a comparable distance-decay trend, suggesting that distinct taxa are likely to exhibit a similar spatial distribution. In addition, the community formation in TGR was influenced by both deterministic and stochastic factors, with the balance between them being mainly controlled by the season. Specifically, deterministic processes could explain 33.9-51.1% of community variations, while stochastic processes could contribute 23.5-32.2%. The findings of this research demonstrated that the varying ecological processes' significance relied on environmental gradients, geographical scale, and ecological conditions. This could offer a fresh outlook on comprehending the composition, assembly mechanisms, and distribution patterns of microeukaryotic plankton in reservoir ecosystems.


Assuntos
Plâncton , Estações do Ano , China , Monitoramento Ambiental , RNA Ribossômico 18S
7.
Ann Surg Oncol ; 31(8): 5011-5020, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38520581

RESUMO

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metástase Linfática , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Idoso , Seguimentos , Prognóstico , Adulto , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Idoso de 80 Anos ou mais , Excisão de Linfonodo , Pneumonectomia , Radiômica
8.
Gene ; 911: 148358, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38467313

RESUMO

BACKGROUND: Paired-like Homeobox 2B (PHOX2B) is considered the causative gene of Congenital Central Hypoventilation Syndrome (CCHS), a dominant genetic disorder characterized by impaired central respiratory control and subsequent hypoventilation during sleep. METHODS: Herein, we present a family with recurrent severe CCHS. The potential causative genetic variant was confirmed through Whole-Exome Sequencing (WES), Sanger sequencing, and droplet digital PCR (ddPCR). Furthermore, prenatal diagnosis was performed on the proband's mother at 20 weeks of her fourth pregnancy upon request. RESULTS: The proband and her brother were both carriers of the PHOX2B polyalanine expansion variant: c.744_758dupCGCGGCAGCGGCGGCGGCGGC. Sanger sequencing revealed that the proband's father had a small variant peak in the gene position, implying potential somatic mosaicism. In addition, ddPCR results showed that the proband's father had germline mosaicism, with a mosaicism proportion of 14.3%. Notably, the detect p.(Ala241[26]) variant was not detected in the fetus. CONCLUSIONS: These findings have important implications for improving genetic counseling of CCHS families as they suggest that even parents without CCHS symptoms may have somatic chimerism, necessitating careful genetic counseling and consideration of prenatal testing for subsequent pregnancies.


Assuntos
Proteínas de Homeodomínio , Hipoventilação , Hipoventilação/congênito , Apneia do Sono Tipo Central , Humanos , Masculino , Feminino , Gravidez , Hipoventilação/genética , Proteínas de Homeodomínio/genética , Mosaicismo , Mutação , Alanina , Fatores de Transcrição/genética , Pai
9.
Sci Rep ; 14(1): 2776, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307983

RESUMO

Autistic children often exhibit atypical brain lateralization of language processing, but it is unclear what aspects of language contribute to this phenomenon. This study employed functional near-infrared spectroscopy to measure hemispheric lateralization by estimating hemodynamic responses associated with processing linguistic and non-linguistic auditory stimuli. The study involved a group of autistic children (N = 20, mean age = 5.8 years) and a comparison group of nonautistic peers (N = 20, mean age = 6.5 years). The children were presented with stimuli with systematically decreasing linguistic relevance: naturalistic native speech, meaningless native speech with scrambled word order, nonnative speech, and music. The results revealed that both groups showed left lateralization in the temporal lobe when listening to naturalistic native speech. However, the distinction emerged between autism and nonautistic in terms of processing the linguistic hierarchy. Specifically, the nonautistic comparison group demonstrated a systematic reduction in left lateralization as linguistic relevance decreased. In contrast, the autism group displayed no such pattern and showed no lateralization when listening to scrambled native speech accompanied by enhanced response in the right hemisphere. These results provide evidence of atypical neural specialization for spoken language in preschool- and school-age autistic children and shed new light on the underlying linguistic correlates contributing to such atypicality at the sublexical level.


Assuntos
Transtorno Autístico , Percepção da Fala , Criança , Humanos , Pré-Escolar , Fala/fisiologia , Lateralidade Funcional/fisiologia , Percepção da Fala/fisiologia , Encéfalo/fisiologia
10.
Biol Pharm Bull ; 47(1): 279-291, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38057100

RESUMO

The abnormal activation of the nuclear factor-kappa B (NF-κB)/nod-like receptor family-pyrin domain-containing 3 (NLRP3) signaling pathway is closely related to early brain injury after subarachnoid hemorrhage (SAH). Targeting the NLRP3-inflammasome has been considered an efficient therapy for the local inflammatory response after SAH. Tanshinone IIA (Tan IIA), a major component extracted from Salvia miltiorrhiza, has been reported to have anti-inflammatory effects. The aim of this study was to investigate the effect and mechanism of Tan IIA on early brain injury after SAH. In vivo SAH injury was established by endovascular perforation technique in Sprague-Dawley rats. Limb-placement test and corner turning test were used to measure the behavior. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, hematoxylin-eosin (H&E) staining, and immunofluorescence were used to evaluate the nerve damage. Real-time RT quantitative PCR (RT-qPCR) was used to quantify the levels of inflammatory factors. Western blot was performed for the activation of the NF-κB/NLRP3 pathway. An in vitro SAH model was used to validate the conclusion. We found that the neurobehavioral impairment and cerebral edema in SAH model rats given Tan IIA were alleviated. Further study demonstrated that Tan IIA could inhibit SAH-secondary neuronal apoptosis around hematoma and alleviate brain injury. Tan IIA down-regulated the expression of interleukin-6 (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α, and inhibited the activation of NF-κB. And the overexpression of pro-inflammatory factors NLRP3, IL-1ß, and IL-18 induced after SAH was also reversed by Tan IIA. In conclusions, Tan IIA could inhibit the NF-κB/NLRP3 inflammasome activation to protect and ameliorate SAH-followed early brain injury, and may be a preventive and therapeutic strategy against SAH.


Assuntos
Abietanos , Lesões Encefálicas , Hemorragia Subaracnóidea , Ratos , Animais , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/patologia , Ratos Sprague-Dawley , Lesões Encefálicas/patologia
11.
Nat Rev Cancer ; 24(1): 72-87, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38040850

RESUMO

Systemic antiplatelet treatment represents a promising option to improve the therapeutic outcomes and therapeutic efficacy of chemotherapy and immunotherapy due to the critical contribution of platelets to tumour progression. However, until recently, targeting platelets as a cancer therapeutic has been hampered by the elevated risk of haemorrhagic and thrombocytopenic (low platelet count) complications owing to the lack of specificity for tumour-associated platelets. Recent work has advanced our understanding of the molecular mechanisms responsible for the contribution of platelets to tumour progression and metastasis. This has led to the identification of the biological changes in platelets in the presence of tumours, the complex interactions between platelets and tumour cells during tumour progression, and the effects of platelets on antitumour therapeutic response. In this Review, we present a detailed picture of the dynamic roles of platelets in tumour development and progression as well as their use in diagnosis, prognosis and monitoring response to therapy. We also provide our view on how to overcome challenges faced by the development of precise antiplatelet strategies for safe and efficient clinical cancer therapy.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Plaquetas/patologia , Plaquetas/fisiologia , Imunoterapia
12.
Front Oncol ; 13: 1227236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023162

RESUMO

Choriocarcinoma is an exceptionally aggressive trophoblastic cell tumor that that typically originates in gonadal tissues, with rare occurrences outside the gonads, including the mediastinum, retroperitoneum, and intracranial sites. However, it rarely occurs in the stomach. Herein, we presented a case of primary gastric choriocarcinoma in a 27-year-old female patient who found multiple liver masses detected during physical examination, accompanied by remarkably elevated human chorionic gonadotropin levels. The 18F-FDG PET/CT scan suggested ring-shaped intense uptake masses located in the gastric sinus and liver, and no significance in the pelvic region. Final histopathology indicated primary choriocarcinoma of the stomach. This case illustrates that 18F-FDG PET/CT is an essential imaging technique for the clinical diagnosis and stage of primary choriocarcinoma.

13.
Bioconjug Chem ; 34(10): 1894-1901, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37787935

RESUMO

As a pleiotropic cytokine, interleukin-2 (IL-2) can effectively regulate lymphocyte proliferation, survival, and active antitumor immune responses in tumor microenvironments. Although the ability of IL-2 to boost immune responses was reported in cancer patients, its short circulating half-life and high toxicity hinder its broad and continual clinical application. Herein, we developed a novel tumor target agent by fusing pH low insertion peptides (pHLIP) with IL-2, forming the fusion protein pHLIP-IL2. Based on the low pH insertion property of pHLIP, the pHLIP-IL2 fusion protein could be selectively delivered to the acidic tumor microenvironments and then promote the proliferation of killer immune cells to elicit tumor regression. We found that pHLIP-IL2 fusion proteins can be significantly enriched in tumor tissues and can effectively reduce tumor size in diverse tumor models, including breast cancer and melanoma, without apparent adverse effects. These data suggest that the pHLIP-IL2 fusion protein may be a promising solution for the continual and extensive application of IL-2, and pHLIP-IL2 is a potential and valuable therapeutic drug for cancer patients with antitumor immunotherapy.


Assuntos
Interleucina-2 , Melanoma , Humanos , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Imunoterapia , Interleucina-2/administração & dosagem , Melanoma/tratamento farmacológico , Microambiente Tumoral , Sistemas de Liberação de Medicamentos
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(11): 1425-1429, 2023 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-37906154

RESUMO

OBJECTIVE: To carry out genetic analysis for a Chinese pedigree affected with intellectual disability and overgrowth due to a supernumerary marker chromosome (sSMC). METHODS: A pedigree which had presented at Jiaxing Maternity and Child Health Care Hospital on August 31, 2021 was selected as the study subject, for which chromosomal karyotyping, single nucleotide polymorphism-based microarray (SNP-array), and fluorescence in situ hybridization (FISH) were carried out in combination. RESULTS: SNP-array analysis showed that the proband and his sister had both harbored a 16.1 Mb duplication which encompassed the critical region of 15q26 overgrowth syndrome. FISH confirmed that the proband was 47,XX,+neo(15)(qter→q25.3:)mat, her mother was 47,XX,del(15)(q25.3:),+neo(15)(qter→q25.3:), whilst her father was normal. CONCLUSION: Application of multiple genetic techniques has facilitated delineation of the origin of sSMC and reliable genetic counseling for this pedigree.


Assuntos
Duplicação Cromossômica , Cromossomos , População do Leste Asiático , Deficiência Intelectual , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Linhagem , Polimorfismo de Nucleotídeo Único , Deficiência Intelectual/genética , Duplicação Cromossômica/genética , Masculino
15.
Endocr Connect ; 12(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37855387

RESUMO

Purpose: The aim was to investigate the effect of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on male gonadal function. Methods: PubMed, Embase, Web of Science, OVID, Scopus, and Wanfang databases were searched up to June 10, 2022, to identify published studies related to RAI and male gonadal function. ReviewManager version 5.4.1 software was used to calculate mean differences (MDs) with 95% CIs. Results: Initially, 1958 articles were retrieved from the databases, and 6 articles were included in the quantitative analysis. The meta-analysis results showed that follicle-stimulating hormone (FSH) increased when the follow-up duration was ≥12 months after RAI, but the difference was not statistically significant (MD = -2.64, 95% CI = (-5.61, 0.33), P = 0.08). But the results of the subgroup analysis showed that when the follow-up time was ≤6 months, FSH levels were significantly higher after RAI (MD = -7.65, 95% CI = (-13.95, -1.34), P = 0.02). The level of inhibin B was significantly lower at ≥12 months and ≤6 months after RAI (MD = 66.38, 95% CI = (8.39, 124.37), P = 0.02) and (MD = 116.27, 95% CI = (43.56, 188.98), P = 0.002). Additionally, luteinizing hormone (LH) and testosterone have similar results - that is, LH and testosterone levels were higher after RAI, but the difference was not statistically significant (MD = -0.87, 95% CI = (-2.04, 0.30), P = 0.15) and (MD = -1.69, 95% CI (-7.29, 3.90), P = 0.55). Conclusions: Male gonadal function may be temporarily impaired within 6 months after RAI but may return to normal levels afterward.

16.
Fish Shellfish Immunol ; 141: 109091, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37722444

RESUMO

The increasing experimental evidence suggests that there are some forms of specific acquired immunity in invertebrates, in which Toll-like receptors (TLRs) play vital roles in activating innate and adaptive immunity and have been comprehensively investigated in mammalian species. Yet, the immune mechanisms underlying TLR mediation in mollusks remain obscure. In this study, we identified a TLR13 gene in the pearl oyster Pinctada fucata for the first time and named it PfTLR13 which consists of a 5'-untranslated terminal region (5'-UTR) of 543 bp, an open reading frame (ORF) of 2667 bp, and a 3'-UTR of 729 bp. We found that PfTLR13 mRNA was expressed in all tissues examined, with the highest level in the gills. The expression of PfTLR13 in the gills of oysters exposed to Vibrio alginolyticus or pathogen-associated molecular patterns (PAMPs) (including LPS, PGN, and poly(I:C)) was significantly higher than in the control group. Interestingly, the immune response to the first stimulation was weaker than the response to the second stimulation, suggesting that the primary stimulation may lead to immune priming of TLR in pearl oysters, similar to acquired immunity in vertebrates. Furthermore, we found that PfTLR13 expression was differentially associated with allograft and xenograft in the pearl oyster P. fucata, with the highest expression levels observed at 12 h post-allograft and 24 h post-xenograft. Overall, our findings provide new insights into the immune mechanisms underlying TLR mediation in mollusks and suggest that PfTLR13 may play a crucial role in the specific acquired immunity of pearl oysters.


Assuntos
Pinctada , Humanos , Animais , Pinctada/genética , Sequência de Aminoácidos , Clonagem Molecular , Imunidade Inata/genética , Imunidade Adaptativa , Receptores Toll-Like/genética , Mamíferos
17.
Cell Rep Methods ; 3(7): 100513, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37533637

RESUMO

A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to be a critical earlier trigger for cancer-associated thrombus formation. However, there currently is no viable approach to monitor specific changes in tumor-associated platelet activity. Here, we describe a chromatograph-like microfluidic device that is highly sensitive to the activity status of peripheral circulating platelets in both tumor-bearing mice and clinical cancer patients. Our results show a strongly positive correlation between platelet activation status and tumor progression. Six-month follow-up data from advanced cancer patients reveal positive links between platelet activity level and thrombus occurrence rate, with a high predictive capacity of thrombotic events (AUC = 0.842). Our findings suggest that circulating platelet activity status determined by this microfluidic device exhibits sensitive, predictive potential for thrombotic events in cancer patients for directing well-timed antithrombosis treatment.


Assuntos
Neoplasias , Trombose , Camundongos , Animais , Plaquetas/patologia , Ativação Plaquetária/fisiologia , Trombose/etiologia , Neoplasias/complicações
18.
Nat Commun ; 14(1): 4898, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580346

RESUMO

Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we develop a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generate a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implement allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields.


Assuntos
Oligonucleotídeos , Transdução de Sinais , Regulação Alostérica , Conformação Molecular
19.
Front Endocrinol (Lausanne) ; 14: 1215751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547313

RESUMO

Background: Long-term impact of sepsis on whole body systems is not well investigated. The aim of the study was to explore the potential association of neonatal/adult sepsis with several inflammation-related diseases in multiple physiological systems. Methods: Instrumental variables for neonatal and adult sepsis were collected from the public genome-wide association studies, which must satisfy the correlation, exclusivity and independence assumptions. Mendelian randomization methods (including random-effect inverse-variance weighted, MR-PRESSO, weighted median and MR-Egger) were used to determine the genetic association of neonatal/adult sepsis with asthma, allergy, rheumatoid arthritis, body mass index/obesity, type 1/type 2 diabetes and intelligence/dementia. Sensitivity analyses were conducted to assess heterogeneity and horizontal pleiotropy. The study was performed by TwoSampleMR in R software. Results: The inverse-variance weighted method reported that neonatal sepsis was related to the decreased level of body mass index (OR = 0.988, 95%CI = 0.980 ~ 0.997, P = 0.007), and adult sepsis was related to the decreased risk of obesity (OR = 0.785, 95%CI = 0.655 ~ 0.940, P = 0.009). These results were supported by the other Mendelian randomization methods. In addition, the study did not find any association of neonatal/adult sepsis with the other inflammation-related diseases. No heterogeneity and horizontal pleiotropy were found using sensitivity analyses. Conclusion: Sepsis had the potential to reduce the risk of obesity or body mass index level at a genetic level, both in neonates and in adults.


Assuntos
Diabetes Mellitus Tipo 2 , Sepse , Adulto , Recém-Nascido , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Sepse/complicações , Sepse/genética , Obesidade
20.
Exp Ther Med ; 26(2): 361, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37408861

RESUMO

The prognostic impact of baseline C-reactive protein (CRP) in patients with cancer receiving immune checkpoint inhibitors (ICIs) is unclear. The present meta-analysis aimed to review the prognostic value of baseline C-reactive protein (CRP) levels for patients with cancer receiving immunotherapy. Electronic databases, including PubMed, EMbase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, WanFang, Chinese Literature Biomedical Database and Weipu Database, were used to identify cohort studies on the relationship between the baseline CRP levels and ICI survival outcomes from inception to November 2020. Literature screening, data extraction and quality evaluation of studies were independently performed by two reviewers. Subsequently, a meta-analysis was performed using STATA 14.0. A total of 13 cohort studies comprising 2,387 patients with cancer were included in the present meta-analysis. The results indicated that high baseline CRP levels (serum CRP measured within 2 weeks before ICI treatment) were associated with low overall survival (OS) and progression-free survival (PFS) rate among patients treated with ICIs. The subgroup analysis based on cancer type showed that high baseline CRP levels were associated with poor survival outcomes of multiple types of cancer, such as non-small cell lung cancer (6/13; 46.2%), melanoma (2/13; 15.4%), renal cell (3/13; 23.0%) and urothelial carcinoma (2/13; 15.4%). Similar results were observed in subgroup analysis based on the CRP cut-off value of 10 mg/l. In addition, a higher mortality risk was reported in patients with cancer and CRP ≥10 mg/l (hazard ratio, 2.76; 95% CI, 1.70-4.48; P<0.001). Compared with patients with low baseline CRP levels, increased baseline CRP levels were associated with low OS and PFS rate in patients with cancer receiving ICIs. Furthermore, CRP ≥10 mg/l indicated a worse prognosis. Therefore, baseline CRP levels may serve as a marker for the prognosis of patients with certain types of solid tumor treated with ICIs. Due to the limited quality and quantity of included studies, more prospective well-designed studies are required to verify the present findings.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...