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1.
Biomark Res ; 11(1): 1, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600320

RESUMO

BACKGROUND: Metastasis is a significant factor that affects the survival of patients with non-small cell lung cancer (NSCLC). Nevertheless, the molecular regulatory mechanism underlying the metastasis is currently not fully understood. This study aims to identify the important role of miR-124-3p in metastasis of NSCLC, thereby providing a potential therapeutic intervention. METHODS: Exosome secretion was determined by Nanoparticle Tracking Analysis (NTA) and the uptake was measured by fluorescence inverted microscope. The binding mechanism between miR-124-3p and its upstream or downstream target genes was validated experimentally by Luciferase reporter. Cells migration was evaluated by transwell assays. Transcriptome sequencing on A549 was carried out to verify the potential signaling pathway underlying miR-124-3p regulation. Western blotting analysis was used to assess the level of AKT, p-AKT, PI3K, and p-PI3K protein expression in NSCLC cell lines. The role of miR-124-3p to suppress the tumor metastasis was verified in NSCLC xenograft model. RESULTS: Exosomes were more abundant in serum from patients with advanced lung cancer (n = 24 patients) than in these from patients with early-stage lung cancer (n = 30 patients), which suggested the potential correlation between amount of exosome secretion and the metastasis of NSCLC. Interestingly, the exosome release, uptake and the migration of NSCLC cells were notably inhibited by miR-124-3p. LINC00511 suppressed the expression of miR-124-3p to facilitate exosome transport due to its role as the competitive endogenous RNA for miR-124-3p. The miR-124-3p could directly target the 3'-UTR of Rab27a in NSCLC cells to inhibit exosome secretion and thereby prevent cell migration and invasion. Aside from the inhibition of exosome transport, miR-124-3p inhibited the activation of PI3K/AKT signaling in the intracellular environment. Finally, by measuring subcutaneous tumor weight and volume and lung metastasis, we also demonstrated that miR-124-3p inhibited tumor growth in vivo. CONCLUSION: In NSCLC, miR-124-3p significantly suppressed metastasis through extracellular exosome transport and intracellular PI3K/AKT signaling. These findings provide new insights toward a better understanding of the NSCLC metastasis and suggest a potential treatment biomarker for NSCLC.

2.
Nutrients ; 15(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36615879

RESUMO

BACKGROUND: The dietary inflammatory index (DII) is thought to be related to many healthy events. However, the association between the DII and sarcopenia remains unclear. METHODS: The meta-analysis was conducted to evaluate the effects of the DII on the risk of sarcopenia utilizing available studies. Up to September 2022, Cochrane, PubMed, Web of Science, Medline, and EMBASE databases were searched to evaluate the relationships between the DII and sarcopenia. A random‒effects model was used to calculate the effect size and 95% confidence intervals (CIs). RESULT: Eleven studies with 19,954 participants were included in our meta-analysis. The results indicated that a high DII increased the risk of sarcopenia (OR = 1.16, 95%CI [1.06, 1.27], p < 0.05). The result of the dose-response analysis showed that the risk of sarcopenia increased by 1.22 times for each 1-point increase in the DII score (OR = 1.22, 95%CI [1.12, 1.33], p < 0.05). CONCLUSION: The meta-analysis demonstrated that the DII is associated with sarcopenia. Considering some limitations in this study, more studies are needed to verify this relationship.


Assuntos
Inflamação , Sarcopenia , Humanos , Fatores de Risco , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Dieta/efeitos adversos , Nível de Saúde
3.
J Environ Manage ; 331: 117303, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36681032

RESUMO

Payment for ecosystem services (PES) plays a vital role in coordinating the relationship between ecosystem services supply and demand sides in watersheds. The upstream soil retention service brings significant off-site benefits to the downstream stakeholders. To fill gaps in the supply and demand of soil retention services for PES, we developed an approach that combined long-term observation data, hydrological model, and cost-benefit analysis. We applied and demonstrated the approach in a typical drinking water source watershed. By constructing the relationship between water clarity and the demanded trophic state, we identified the demand for soil retention as the suspended sediment concentration ≤4.4 mg L-1 at a transboundary station. Then, a well-calibrated hydrological model was applied to simulate the downstream sediment reduction under 36 upstream reforestation scenarios. Results showed that cropland reforestation effectively reduced downstream sediment loads by up to 37.8%. However, the efficiency of cropland reforestation for soil retention supply was influenced by its area, slope, and location. The cost-benefit analysis revealed that the feasible sediment reduction was 11,000 t per year, and the market-equilibrium price was 5800 CNY (Chinese Yuan, 7 CNY equaled 1 USD in 2020) per ton. The downstream side should pay 64 million CNY annually for soil retention provided by reforesting at upstream sloping cropland of 8° or above. This study suggested that the approach was helpful for integrating soil retention service supply and demand at a watershed scale to support PES decision-making.

4.
Hypertens Res ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690806

RESUMO

Our study aims to investigate the alterations and diagnostic efficiency of regional homogeneity (ReHo) and functional connectivity (FC) in hypertension patients with cognitive impairment. A total of 62 hypertension patients with cognitive impairment (HTN-CI), 59 hypertension patients with normal cognition (HTN-NC), and 58 healthy controls (HCs) with rs-fMRI data were enrolled in this study. Univariate analysis (based on whole-brain ReHo and seed-based FC maps) was performed to observe brain regions with significant differences among the three groups. Multiple voxel pattern analysis (MVPA) was applied to evaluate the diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. Compared with the HCs and HTN-NC, HTN-CI exhibited decreased ReHo in the right caudate, left postcentral gyrus, posterior cingulate gyrus, insula, while increased ReHo in the left superior occipital gyrus and superior parietal gyrus. HTN-CI showed increased FC between seed regions (left posterior cingulate gyrus, insula, postcentral gyrus) with many specific brain regions. MVPA analysis (based on whole-brain ReHo and seed-based FC maps) displayed high classification ability in distinguishing HTN-CI from HTN-NC and HCs. The ReHo values (right caudate) and the FC values (left postcentral gyrus seed to left posterior cingulate gyrus) were positively correlated with the MoCA scores in HTN-CI. HTN-CI was associated with decreased ReHo and increased FC mainly in the left posterior cingulate gyrus, postcentral gyrus, insula compared to HTN-NC and HC. Besides, MVPA analysis yields excellent diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. The findings may contribute to unveiling the underlying neuropathological mechanism of HTN-CI.

5.
J Clin Med ; 12(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36675472

RESUMO

BACKGROUND: Coronary slow flow (CSF) is an angiographic entity characterized by delayed coronary opacification with no evident obstructive lesion in the epicardial coronary artery. Several studies have shown that the occurrence and development of CSF may be closely related to inflammation. Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a biomarker related to inflammation. The aim of this study was to evaluate the correlation between plasma soluble VCAM-1 level and CSF occurrence and thus the predictive value of VCAM-1 for CSF. METHODS: Forty-six CSF patients and thirty control subjects were enrolled. Corrected thrombolysis in myocardial infarction frame count (cTFC) was used to diagnose CSF. Functional status and quality of life were determined by the Seattle Angina Questionnaire (SAQ). Echocardiography was used to evaluate the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV). The plasma levels of sVCAM-1, IL-6, and TNF-α were quantified by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the physical limitation score by the SAQ, the LV global longitudinal strain (GLS), mitral E, and mitral E/A decreased in patients with CSF, while the plasma IL-6 and TNF-α levels increased. The plasma sVCAM-1 level in the CSF group was significantly higher than that in the control group (186.03 ± 83.21 vs. 82.43 ± 42.12 ng/mL, p < 0.001), positively correlated with mean cTFC (r = 0.57, p < 0.001), and negatively correlated with the physical limitation score (r = -0.32, p = 0.004). Logistic regression analyses confirmed that plasma sVCAM-1 level (OR = 1.07, 95%CI: 1.03-1.11) is an independent predictor of CSF, and the receiver operating characteristic curve analysis showed that plasma sVCAM-1 levels had statistical significance in predicting CSF (area under curve = 0.88, p < 0.001). When the sVCAM-1 level was higher than 111.57 ng/mL, the sensitivity for predicting CSF was 87% and the specificity was 73%. CONCLUSIONS: Plasma sVCAM-1 level can be used to predict CSF and was associated with the clinical symptoms of patients. It may serve as a potential biomarker for CSF in the future.

6.
J Biol Eng ; 17(1): 8, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717887

RESUMO

Hydrogels, also known as three-dimensional, flexible, and polymer networks, are composed of natural and/or synthetic polymers with exceptional properties such as hydrophilicity, biocompatibility, biofunctionality, and elasticity. Researchers in biomedicine, biosensing, pharmaceuticals, energy and environment, agriculture, and cosmetics are interested in hydrogels. Hydrogels have limited adaptability for complicated biological information transfer in biomedical applications due to their lack of electrical conductivity and low mechanical strength, despite significant advances in the development and use of hydrogels. The nano-filler-hydrogel hybrid system based on supramolecular interaction between host and guest has emerged as one of the potential solutions to the aforementioned issues. Black phosphorus, as one of the representatives of novel two-dimensional materials, has gained a great deal of interest in recent years owing to its exceptional physical and chemical properties, among other nanoscale fillers. However, a few numbers of publications have elaborated on the scientific development of black phosphorus hybrid hydrogels extensively. In this review, this review thus summarized the benefits of black phosphorus hybrid hydrogels and highlighted the most recent biological uses of black phosphorus hybrid hydrogels. Finally, the difficulties and future possibilities of the development of black phosphorus hybrid hydrogels are reviewed in an effort to serve as a guide for the application and manufacture of black phosphorus -based hydrogels. Recent applications of black phosphorus hybrid hydrogels in biomedicine.

7.
Nat Commun ; 14(1): 393, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693823

RESUMO

Three-terminal thermal analogies to electrical transistors have been proposed for use in thermal amplification, thermal switching, or thermal logic, but have not yet been demonstrated experimentally. Here, we design and fabricate a three-terminal magnetic thermal transistor in which the gate temperature controls the source-drain heat flow by toggling the source-drain thermal conductance from ON to OFF. The centimeter-scale thermal transistor uses gate-temperature dependent magnetic forces to actuate motion of a thermally conducting shuttle, providing thermal contact between source and drain in the ON state while breaking contact in the OFF state. We measure source-drain thermal switch ratios of 109 ± 44 in high vacuum with gate switching temperatures near 25 °C. Thermal measurements show that small heat flows into the gate can be used to drive larger heat flows from source to drain, and that the switching is reversible over >150 cycles. Proof-of-concept thermal circuit demonstrations show that magnetic thermal transistors can enable passive or active heat flow routing or can be combined to create Boolean thermal logic gates. This work will allow thermal researchers to explore the behavior of nonlinear thermal circuits using three-terminal transistors and will motivate further research developing thermal transistors for advanced thermal control.

8.
Plant J ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602036

RESUMO

Saururus chinensis, an herbaceous magnoliid without perianth, represents a clade of early-diverging angiosperms that have gone through woodiness-herbaceousness transition and pollination obstacles: the characteristic white leaves underneath inflorescence during flowering time are considered to be a substitute for perianth to attract insect pollinators. Here, using the newly sequenced S. chinensis genome, we revisited the phylogenetic position of magnoliids within mesangiosperms, and recovered a sister relationship for magnoliids and Chloranthales. By considering differentially expressed genes, we identified candidate genes that are involved in the morphogenesis of the white leaves in S. chinensis. Among those genes, we verified - in a transgenic experiment with Arabidopsis - that increasing the expression of the 'pseudo-etiolation in light' gene (ScPEL) can inhibit the biosynthesis of chlorophyll. ScPEL is thus likely being responsible for the switches between green and white leaves, suggesting that changes in gene expression may underlie the evolution of pollination strategies. Despite being an herbaceous plant, S. chinensis still has vascular cambium and maintains the potential for secondary growth as a woody plant, because the necessary machinery, i.e., the entire gene set involved in lignin biosynthesis, is well preserved. However, similar expression levels of two key genes (CCR and CAD) between the stem and other tissues in the lignin biosynthesis pathway are possibly associated with the herbaceous nature of S. chinensis. In conclusion, the S. chinensis genome provides valuable insights into the adaptive evolution of pollination in Saururaceae and reveals a possible mechanism for the evolution of herbaceousness in magnoliids.

9.
Neural Regen Res ; 18(3): 664-670, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018192

RESUMO

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

10.
Aquat Toxicol ; 254: 106371, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36529091

RESUMO

Benzophenone-type UV filters (BPs) are ubiquitous contaminants in aquatic environments, possibly posing ecological risks to aquatic populations. So far, little is known about the potential adverse effects of BPs on amphibians. Given their potential estrogenic property, we investigated the detrimental effects of the commonly used BPs, BP-3, BP-2, and BP-1, on testis development in amphibians using Xenopus laevis as a model species. Following exposure to 10, 100, 1000 nM BP-3, BP-2, or BP-1 from stages 45/46 to 52, tadpoles presented morphological abnormal testes, characterized by reduced gonomere size and testis area, coupled with suppressed cell proliferation. Meanwhile, the downregulation of testis-biased gene expression and the upregulation of ovary-biased gene expression were observed in BPs-treated testes. Moreover, the estrogen receptor (ER) antagonist ICI 182780 significantly antagonized ovary-biased gene upregulation caused by BPs, suggesting that the effects of BPs on testis differentiation could be mediated by ER, at least partially. Of note, the effects of BPs were not concentration-dependent, but the lowest concentration generally exerted significant effects. Altogether, these observations indicate that the three BPs inhibited testis differentiation and exerted feminizing effects. Importantly, when BP-2 exposure was extended to two months post-metamorphosis, testes of froglets were generally less-developed, with relatively fewer spermatocytes, more spermatogonia, and poorly formed seminiferous tubules. Considering the fact that the lowest concentration (10 nM) of BPs in this study are detectable in aquatic environments, we conclude that BP-3, BP-2, and BP-1, even at environmentally relevant concentrations, can retard testis differentiation at pre-metamorphic stages and cause testis dysgenesis after metamorphosis in the amphibian X. laevis. Our findings suggest that ubiquitous BPs in aquatic environments could pose a potential risk to amphibians.


Assuntos
Testículo , Poluentes Químicos da Água , Masculino , Animais , Feminino , Xenopus laevis , Poluentes Químicos da Água/toxicidade , Ovário , Benzofenonas/toxicidade
11.
J Antimicrob Chemother ; 78(2): 521-530, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36575565

RESUMO

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has spread worldwide and has become a major threat to public health. The restriction modification system provides an innate defence of bacteria against plasmids or transposons, while many different types of plasmid encoding the anti-restriction protein ArdA can specifically affect the restriction activity in bacteria. OBJECTIVES: To detect the codistribution of ArdA and blaKPC-2 plasmids in KPC-KP and explore the molecular mechanism of ArdA promoting KPC-KP spread. METHODS: We collected 65 clinical CRKP isolates from Ningbo, China, and 68 cases of plasmid complete sequences in GenBank to determine the prevalence of ArdA gene on the K. pneumoniae blaKPC-2 plasmid. The anti-restriction function of ArdA in promoting horizontal gene transfer (HGT) was verified by transformation, conjugation and transduction methods, and the pull-down experiment was used to investigate the molecular mechanism of ArdA protein in vitro. RESULTS: We found that ArdA was widely distributed in KPC-KP in 100% of cases, which was detected in 0% of drug susceptible K. pneumoniae, and the plasmids containing the ArdA gene in 90% of the 30 cases randomly retrieved from the database. We also verified that ArdA has a good anti-restriction function (P < 0.05) through two aspects of HGT (transformation, transduction), and explored the non-occurrence interaction of ArdA and the hsdM subunit protein of EcoKI enzyme from the perspective of protein molecules. CONCLUSIONS: These findings suggest that the coexistence advantage of ArdA with the blaKPC-2 plasmids may provide KPC-producing K. pneumoniae with a very efficient evasion of the restriction of type I systems, which not only favours ArdA-containing mobile genetic elements in the same species HGT between bacteria also facilitates HGT between other bacterial species.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella/genética , Infecções por Klebsiella/microbiologia , Epidemiologia Molecular , Proteínas de Bactérias/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Plasmídeos
12.
ACS Sens ; 8(1): 51-60, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36573608

RESUMO

The Warburg effect suggests that upregulated glycolysis arising from high glucose uptake in cancer cells might be accompanied with suppressed mitochondrial respiration. However, recent studies have shown that the mitochondrial temperature in cancer cells could be relatively higher than that in normal cells, suggesting hyperactive mitochondrial respiration in cancer cells. However, hot mitochondria have not been reported in patients with cancer. Here, near-infrared small-molecule fluorescent probes TRNs are rationally designed with two ethyl amino groups as the temperature-sensitive moiety. Afterward, a mitochondrial targeting group is installed via ether bonds on TRN-8 to build MTN. To the best of our knowledge, MTN is the near-infrared probe with the highest sensitivity for mitochondrial temperature. Moreover, it also displays high photostability, wide linearity, and high specificity. Using MTN, we can monitor the ups and downs of mitochondrial temperature in cancer cells upon the perturbations of mitochondrial respiration. Furthermore, we demonstrate that the mitochondrial temperature in surgically resected human tumors is relatively higher than that in paracancerous tissues. Our results indicate that relatively hot mitochondria may exist in tumors from patients. We envisage that our study provides critical evidence for revisiting the Warburg effect and cancer metabolism.


Assuntos
Neoplasias , Termômetros , Humanos , Mitocôndrias/metabolismo , Glicólise , Neoplasias/patologia , Corantes Fluorescentes/química
13.
Poult Sci ; 102(2): 102374, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529101

RESUMO

Follicular atresia is a natural physiological phenomenon in poultry reproduction. It is well known that follicular atresia is caused by both autophagy and apoptosis of granulosa cells. In current experiment, we evaluated the function of miR-34a-5p on autophagy and apoptosis in chicken follicular atresia. First, the follicular atresia model of chicken was successfully constructed by subcutaneous injection of tamoxifen (TMX), and found the expression of miR-34a-5p in the atresia follicles obviously increased. Then, we confirmed that miR-34a-5p accelerates autophagy and apoptosis of chicken granulose cells in vitro, and miR-34a-5p could induce apoptosis by mediating autophagy. Mechanistically, lymphoid enhancer binding factor 1 (LEF1) was deemed as a target gene for miR-34a-5p. On the contrary, LEF1 overexpression attenuated the autophagy and apoptosis of chicken granular cells. In addition, it was confirmed that the miR-34a-5p/LEF1 axis plays a regulatory role in chicken granulosa cells by mediating the Hippo-YAP signaling pathway. Taken together, this study demonstrated that miR-34a-5p contributes to autophagy and apoptosis of chicken follicular granulosa cells by targeting LEF1 to mediate the Hippo-YAP signaling pathway.


Assuntos
MicroRNAs , Animais , Feminino , Apoptose/genética , Autofagia/fisiologia , Proliferação de Células/genética , Galinhas/genética , Galinhas/metabolismo , Atresia Folicular , Células da Granulosa/metabolismo , Via de Sinalização Hippo , Fator 1 de Ligação ao Facilitador Linfoide/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Sinalização YAP/metabolismo
14.
Sci Total Environ ; : 160584, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36455724

RESUMO

Sulfonamides (SAs) are common antibiotics that are widely present in the environment and can easily migrate in the environment, so they pose an environmental risk. Minerals and organic matter influence the antibiotic migration and transformation in sewage treatment plants, activated sludge, surface water, and soil environment. In the present paper, the influence of the process and mechanism of minerals and organic matter on the adsorption, degradation, and plant uptake of SAs in soil were summarized. In the impact process of mineral and organic matter on the SAs migration and transformation, the pH value is undoubtedly the most important factor because it determines the ionic state of SAs. In terms of influence mechanisms, the minerals absorb SAs well via cation exchange, complexation, H-bonding, and cation bridging. Mineral photodegradation is also one of the primary removal methods for SAs. Soil organic matter (SOM) can significantly increase the SAs adsorption. The adsorption forces of SAs and SOM or dissolved organic matter (DOM) were very similar, but SOM decreased SAs mobility in the environment, while DOM increased SAs availability. DOM generated active substances and aided in the photodegradation of SAs. This review describes the effects of minerals and organic matter on the fate of SAs in soil, which is useful in controlling the migration and transformation of SAs in the soil environment.

15.
J Clin Med ; 11(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36498638

RESUMO

(1) Background: Hypertensive patients with obstructive sleep apnea (OSA) are at high risk for cardiovascular diseases (CVDs), and the utility of aspirin for primary cardiovascular prevention in this population remains uncertain. (2) Methods: In this retrospective cohort study using data from the Urumchi Hypertension Database (UHDATA), hypertensive patients older than 18 years old with a first-time diagnosis of OSA were divided into three groups depending on aspirin history. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included MACCE components, ischemic events, cardiac events, cerebrovascular events, and gastrointestinal bleeding risk. The inverse probability of treatment weighting (IPTW) method was used to balance the confounding factors among the groups, and the Cox proportional hazards model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). (3) Results: In persistent aspirin users, the risk of MACCE events (HR 2.11, 95%CI 1.23-3.63), ischemic events (HR 2.58, 95%CI 1.42-4.69), cerebrovascular events (HR 2.55, 95%CI 1.44-4.51), and non-fatal cerebral infarction (HR 3.14, 95%CI 1.69-5.84) was significantly elevated. (4) Conclusions: Continuous aspirin use increases the incidence of cardiovascular adverse events in hypertensive patients with OSA receiving aspirin for primary prevention of cardiovascular disease.

16.
Front Endocrinol (Lausanne) ; 13: 1049211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545329

RESUMO

Background: The current status of the dose-response relationship between the metabolic score for insulin resistance (METS-IR) and new-onset stroke in hypertensive patients and its subtypes is unclear. This study aimed to determine the association between METS-IR and incident stroke and its subtypes within a cohort of Chinese hypertensive patients. Methods: A total of 14032 hospitalized patients with hypertension from January 1, 2010, to December 31, 2021, were included in this retrospective cohort study. Cox models and restricted cubic splines were applied to determine the association between METS-IR and the risk of stroke. Results: During a median follow-up of 4.80 years, 1067 incident stroke cases occurred. Patients in the highest quartile group of METS-IR levels exhibited a higher risk of stroke (HR, 1.80; 95% CI, 1.50-2.17) and ischemic stroke (HR, 1.96; 95% CI, 1.60-2.42) than those in the lowest quartile group. However, no significant associations were observed between METS-IR and the risk of hemorrhagic stroke. Restricted cubic spline analysis suggested a nearly J-shaped association between METS-IR and risk of stroke and ischemic stroke (P for nonlinearity < 0.001). METS-IR did produce a significant improvement in the C statistic when added to the basic model (from 0.637 to 0.664, P < 0.001). Notably, the addition of METS-IR to the basic model resulted in a significant improvement in predicting incident total stroke and ischemic stroke. Conclusions: This cohort study suggests a relationship between METS-IR and the risk of stroke and ischemic stroke. Further studies are required to elucidate the underlying mechanisms.


Assuntos
Hipertensão , Resistência à Insulina , AVC Isquêmico , Síndrome Metabólica , Acidente Vascular Cerebral , Humanos , Resistência à Insulina/fisiologia , Estudos de Coortes , Síndrome Metabólica/metabolismo , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Hipertensão/complicações , Hipertensão/epidemiologia , AVC Isquêmico/epidemiologia , AVC Isquêmico/etiologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-36516963

RESUMO

Coronary slow flow is taken to be indicative of delayed filling of terminal vessels of the coronary arteries in the absence of coronary stenosis, as detected using coronary angiography. Patients suffering from coronary slow flow typically experience recurrent chest pain, thereby markedly affecting their quality of life. The etiology and pathogenesis of coronary slow flow, which is gradually attracting clinical attention, have yet to be sufficiently established, although it is currently believed that they may be associated with endothelial dysfunction in the coronary arteries, inflammatory response, abnormalities in microvascular reserve function, subclinical atherosclerosis, blood cell and platelet abnormalities, and genetic factors. In this review, we provide a brief overview of recent progress in research on the pathogenesis of coronary slow flow with a view toward elucidating the possible underlying pathogenesis and identify targets and directions for the treatment of this condition.

18.
Front Nutr ; 9: 1048206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36562034

RESUMO

Objective: We aimed to investigate the association between the GNRI and the risk of stroke in elderly patients with hypertension. Methods: A total of 5312 elderly hypertensive patients free of history of stroke were included. Multivariate Cox models were used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs) for stroke and its subtypes. Results: The average time of follow-up was 3.8 years, and the median time was 3.2 years. We identified 640 individuals with stroke, of whom 526 had an ischemic stroke (IS) and 114 had a hemorrhagic stroke (HS). After adjusting for confounding variables, compared with participants in the lowest quartile of the GNRI, those in the third and fourth quartiles were associated with a decreased risk of stroke (adjusted HR 0.72, 95% CI 0.58-0.90, and adjusted HR 0.58, 95% CI 0.46-0.74, respectively, P for trend < 0.001). Similar results were found for IS and HS. Moreover, there were L-shaped associations of GNRI with new-onset HS (P for non-linearity = 0.034). Multiple sensitivity analyses and stratified analyses did not materially change the results. Conclusions: In summary, we found that a lower GNRI was associated with a higher risk of incident stroke in elderly hypertensive patients. Additional prospective data collection is required to confirm our findings.

19.
Cancer Med ; 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36524283

RESUMO

BACKGROUND OR PURPOSE: A practical noninvasive method to identify sentinel lymph node (SLN) status in breast cancer patients, who had a suspicious axillary lymph node (ALN) at ultrasound (US), but a negative clinical physical examination is needed. To predict SLN metastasis using a nomogram based on US and biopsy-based pathological features, this retrospective study investigated associations between clinicopathological features and SLN status. METHODS: Patients treated with SLN dissection at four centers were apportioned to training, internal, or external validation sets (n = 472, 175, and 81). Lymph node ultrasound and pathological characteristics were compared using chi-squared and t-tests. A nomogram predicting SLN metastasis was constructed using multivariate logistic regression models. RESULTS: In the training set, statistically significant factors associated with SLN+ were as follows: histology type (p < 0.001); progesterone receptor (PR: p = 0.003); Her-2 status (p = 0.049); and ALN-US shape (p = 0.034), corticomedullary demarcation (CMD: p < 0.001), and blood flow (p = 0.001). With multivariate analysis, five independent variables (histological type, PR status, ALN-US shape, CMD, and blood flow) were integrated into the nomogram (C-statistic 0.714 [95% CI: 0.688-0.740]) and validated internally (0.816 [95% CI: 0.784-0.849]) and externally (0.942 [95% CI: 0.918-0.966]), with good predictive accuracy and clinical applicability. CONCLUSION: This nomogram could be a direct and reliable tool for individual preoperative evaluation of SLN status, and therefore aids decisions concerning ALN dissection and adjuvant treatment.

20.
Front Med ; 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36525138

RESUMO

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

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