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1.
Eur J Med Res ; 28(1): 329, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689707

RESUMO

BACKGROUND: Although the mean arterial pressure (MAP) target of 65 mmHg was achieved, diastolic blood pressure (DBP) was still low in some septic shock patients. The effects of DBP on the prognosis and optimal target for patients with septic shock are unclear. We sought to investigate the relationship between DBP and 28-day mortality in septic shock patients. METHODS: In this retrospective observational study, we obtained data from the Chinese Database in Intensive Care (CDIC). We included patients with an admission diagnosis of septic shock and shock was controlled. DBP was measured every 1 h, and the mean DBP during the first 24 h (mDBP24h) was recorded. The primary outcome was 28-day mortality. Multivariable logistic regression determined the relationship between mDBP24h and 28-day mortality. RESULTS: In total, 1251 patients were finally included. The 28-day mortality of included septic shock patients was 28.3%. The mDBP24h, not mSBP24h, was higher among 28-day survivors compared with non-survivors. 28-day mortality was inversely associated with mDBP24h (unadjusted OR 0.814 per 10 mmHg higher mDBP24h, P = 0.003), with a stepwise increase in 28-day mortality at lower mDBP24h. The 28-day mortality of patients with mDBP24h < 59 mmHg had an absolute risk reduction of 9.4% (P = 0.001). And mDBP24h < 59 mmHg was the remaining high risk factor inversely associated with 28-day mortality after multivariable adjustment (adjusted OR 1.915, 95% CI 1.037-3.536, P = 0.038), while mMAP24h and mSBP24h were not. CONCLUSION: In patients with septic shock after initial resuscitation, we observed an inverse association between mDBP24h and 28-day mortality. The poor outcomes in patients with mDBP24h < 59 mmHg provide indirect evidence supporting a further DBP goal of 59 mmHg for patients with septic shock after MAP of 65 mmHg was achieved.


Assuntos
Choque Séptico , Humanos , Pressão Sanguínea , Ressuscitação , Estudos Retrospectivos , Choque Séptico/mortalidade
2.
Biomark Res ; 11(1): 79, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37674244

RESUMO

BACKGROUND: Growing evidence supports that extracellular vesicles (EVs) in blood plasma and other body fluids may function as biomarkers for disease. We previously found that secretory autophagosomes (SAPs), a kind of EV, could exacerbate lung injury in mice. However, the clinical value of SAPs in acute respiratory distress syndrome (ARDS), the most severe form of lung injury, remains unknown. Our study investigated the prognostic value of secretory autophagosomes in ARDS. METHODS: ARDS patients (n = 46) and controls (n = 8) were included in a prospective monocentric study. Bronchoalveolar lavage fluid (BALF) samples were collected from ARDS patients on the first day (Day 1) or the third day (Day 3) of enrollment and were collected from controls on Day 1. Gradient centrifugation was performed to isolate EVs. The size and concentration of EVs were characterized by nanoparticle tracking analysis (NTA). SAPs in EVs were characterized by flow cytometry, transmission electron microscopy, and western blot analysis, and the proportion of SAPs in EVs (PSV) was measured by flow cytometry. The association of SAPs with 28-day mortality was assessed. RESULTS: On Days 1 and 3, the proportion of SAPs (SAPs%) in BALF was higher in patients with ARDS than in controls. On Day 3, the SAPs% was significantly higher in nonsurvivors than in survivors. In particular, a high SAPs% was associated with poor overall survival in ARDS patients. Furthermore, the combination of SAPs% and SOFA obtained a higher predictive value of ARDS outcome than PSV or SOFA alone. CONCLUSION: SAPs% in BALF is elevated in patients with ARDS and is associated with the risk of death in ARDS, suggesting that SAPs% may be a novel prognostic biomarker in ARDS.

3.
Neuropharmacology ; 240: 109710, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37683885

RESUMO

Pyramidal neuron (Pyn) hyperactivity in the anterior cingulate cortex (ACC) is involved in the modulation of pain. Previous studies indicate that the activation of α2 adrenoceptors (α2-ARs) by dexmedetomidine (DEX) is a safe and effective means of alleviating multiple types of pain. Here, we showed that systemically administered DEX can ameliorate the inflammatory pain induced by hindpaw injection of formalin (FA) and further examined the molecular and synaptic mechanisms of this DEX-elicited antinociceptive effect. We found that FA caused an increase in c-Fos expression in contralateral layer 2/3 (L2/3) ACC, and that intra-ACC infusion of DEX could also relieve phase 2 inflammatory pain behavior. DEX elicited an increase in the amplitude and frequency of miniature inhibitory post-synaptic currents (mIPSCs) and evoked IPSC amplitude, as well as a reduction in the hyperexcitability and both paired-pulse and excitation/inhibition ratios in contralateral L2/3 ACC Pyns of FA mice. These electrophysiological effects were associated with the upregulation of GABA A receptor (GABAAR) subunits. The interaction of phosphorylated Akt (p-Akt) with GABAAR subunits increased in the ACC following administration of DEX. These results suggest that DEX treatment reduces hyperactivity and enhances GABAergic inhibitory synaptic transmission in ACC Pyns, which produces analgesic effects by increasing GABAAR levels and activating the Akt signaling pathway.

4.
Cell Biochem Funct ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37707349

RESUMO

Identifying a functional molecular therapeutic target of vascular calcification (VC) that will not affect normal osteogenic differentiation is a challenge. To address this aim, we screened the differentially expressed genes (DEGs) in different VC conditions, including endothelial-osteogenic transition (EOT) (GSE167962), chronic kidney disease (CKD), and atherosclerosis (AS) (GSE159832). KEGG pathways, protein-protein interactions, and hub genes were also analyzed. The intersecting DEGs among the EOT, CKD, and AS groups were verified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in a DOCA-salt hypertension mouse model. The phosphoinositide 3-kinase-protein kinase B signaling pathway, ECM-receptor interaction, chemokine signaling pathway, and focal adhesion were enriched in EOT and AS-induced VC. ECM-receptor interaction, PPAR signaling pathway, apelin signaling pathway, AMPK signaling pathway, adipocytokine signaling pathway, and cholesterol metabolism were enriched in CKD and AS-induced VC. C4b, Cebpa, Lyz2, and Spp1 were also upregulated in EOT, CKD, AS, and hypertension. This study identified promising molecular targets for VC therapy.

5.
Food Chem ; 434: 137465, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37716148

RESUMO

Lipid oxidation is the major cause of quality deterioration in freshwater fish, especially mediated by myoglobin (Mb). This study aimed to investigate the antioxidant mechanism of Maillard reaction products (MRPs) in Mb-mediated lipid oxidation in common carp (Cyprinus carpio). MRPs exhibited promising antioxidant and antimicrobial capacities based on the reduced content of peroxide and thiobarbituric acid-reactive substances and inhibited microbial growth. MRPs inhibited the oxidation of Mb by lowering the transfer from oxymyoglobin to metmyoglobin and improving the stability of heme iron. The correlation analysis showed that MRPs regulated the formation of free radicals by maintaining the reduced structure of Mb and the integrity of heme iron, and also directly inhibited the formation of oxidation products in a chain radical reaction. The texture and electronic nose analysis indicated that MRPs could delay the structural disruption and flavor deterioration of surimi. Therefore, MRPs could effectively inhibit Mb-induced lipid oxidation and further control the resulting changes in the flavor and texture of surimi.

6.
Mol Pain ; 19: 17448069231204051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37699859

RESUMO

Chronic pain is the most common symptom for people who suffer from rheumatoid arthritis and it affects approximately 1% of the global population. Neuroinflammation in the spinal cord induces chronic arthritis pain. In this study, a collagen-induced arthritis (CIA) mice model was established through intradermally injection of type II collagen in complete Freund's adjuvant solution. Following CIA inducement, the paws and ankles of mice were found to swell, mechanical pain and spontaneous pain were induced, and their motor coordination was impaired. The spinal inflammatory reaction was triggered, which presented as severe infiltration of inflammatory cells, and the expression levels of GFAP, IL-1ß, NLRP3, and cleaved caspase-1 increased. Oxidative stress in the spinal cord of CIA mice was manifested as reduced Nrf2 and NDUFB11 expression and SOD activity, and increased levels of DHODH and Cyto-C. At the same time, spinal AMPK activity was decreased. In order to explore the potential therapeutic options for arthritic pain, Xanthohumol (Xn) was intraperitoneally injected into mice for three consecutive days. Xn treatment was found to reduce the number of spontaneous flinches, in addition to elevating mechanical pain thresholds and increasing latency time. At the same time, Xn treatment in the spinal cord reduced NLRP3 inflammasome-mediated inflammation, increased the Nrf2-mediated antioxidant response, and decreased mitochondrial ROS level. In addition, Xn was found to bind with AMPK via two electrovalent bonds and increased AMPK phosphorylation at Thr174. In summary, the findings indicate that Xn treatment activates AMPK, increases Nrf2-mediated antioxidant response, reduces Drp1-mediated mitochondrial dysfunction, suppresses neuroinflammation, and can serve to relieve arthritis pain.

7.
Plant J ; 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37753665

RESUMO

Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.

8.
Ann Intensive Care ; 13(1): 93, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37755544

RESUMO

BACKGROUND: Limited data are available on renal complications in patients with acute fulminant myocarditis (AFM) receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in China. To evaluate the impact of renal complications on outcomes in adult patients with AFM supported with VA-ECMO. METHODS: Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Adult patients who were diagnosed with AFM receiving VA-ECMO support in the database were included. The primary outcome was 30-day mortality in patients with AFM supported with VA-ECMO. Logistic regression model was used to examine the impact of renal complications on 30-day mortality by adjusting confounders. RESULTS: A total of 202 patients were included. The median age was 38 years (IQR 29-48) and males (n = 103) represented 51.0% of the total accounted patients. The median ECMO duration was 142.9 h (IQR 112.1-188.8 h). 178 (88.1%) patients weaned from ECMO and 156 (71.9%) patients survived. 94(46.5%) patients developed renal complications while on ECMO course. Patients with renal complications had higher 30-day mortality (40.7% (37 of 94) vs 8.3% (9 of 108), P < 0.001) compared with those without. The development of renal complications was related to a 3.12-fold increase risk of 30-day mortality (adjusted OR 3.120, 95%CI 1.002-6.577, P = 0.049). Increasing age (adjusted OR1.025, 95% CI 1.008-1.298, P = 0.040) and higher SOFA score (adjusted OR 1.162, 95%CI 1.012-1.334, P = 0.034) were independent risk factors of renal complications. CONCLUSIONS: Our findings demonstrated that patients with AFM receiving VA-ECMO at high risk of developing renal complications. Advancing age and higher SOFA score was associated with increased risk of developing renal complications. The onset of renal complications was significantly associated with 30-day mortality.

9.
J Diabetes ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37746907

RESUMO

OBJECTIVES: The purpose of our investigation is to evaluate the level of relationship between lactate dehydrogenase (LDH) and the occurrence of diabetic retinopathy (DR) in adults with diabetes mellitus (DM). METHODS: The investigation involved an analysis of five sectional data cycles acquired from the National Health and Nutrition Examination Survey from 2009 to 2018. The present study involved the selection of DM samples from a complex multistage probability sample. These samples were subsequently classified into two distinct groups, namely the No DR (NDR) and DR groups. The present study comprehensively investigated the biological and social risk factors associated with DR. The biological factors examined in this investigation included blood pressure, blood routine, hemoglobin A1c, blood glucose, and comorbidities. The social dimensions encompass education and sex. RESULTS: After considering all factors, multivariate regression models indicated a significant relationship between DR and increased LDH (adjusted odds ratio = 1.007, 95% confidence interval: 1.003-1.011). The subgroup analysis revealed that the effect size of LDH on the existence of DR in the subgroups remained consistent, as indicated by all p values greater than .05. A statistically significant relationship was identified between elevated LDH levels > 134 U/L and a raised risk of DR in people with DM. CONCLUSION: LDH concentrations were connected with an increased prevalence of DR in participants with DM. Our study highlights that patients with LDH > 134 U/L are distinguishably related to DM complicated by DR. DR is more common in diabetic individuals with coronary heart disease.

10.
Adv Mater ; : e2304638, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37681325

RESUMO

Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. We developed a powerful platform technology combining magneto-responsive hydrogel, cells, and wireless magneto-induced dynamic mechanical stimulation (MDMS) to accelerate diabetic wound healing. Our hydrogel encapsulates FDA-approved fibroblasts and keratinocytes to achieve ∼3-fold better wound closure in a diabetic mouse model. MDMS acts as a non-genetic mechano-rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto-responsive property also enables on-demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, we identified a mechanosensitive fibroblast subpopulation that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. Our "all-in-one" system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types. This article is protected by copyright. All rights reserved.

11.
Mol Neurobiol ; 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37676391

RESUMO

Ferroptosis is a distinct peroxidation-driven form of cell death tightly involved in subarachnoid hemorrhage (SAH). This study delved into the mechanism of deferoxamine (DFO, an iron chelator) in SAH-induced ferroptosis and inflammation. SAH mouse models were established by endovascular perforation method and injected intraperitoneally with DFO, or intraventricularly injected with the Nrf2 pathway inhibitor ML385 before SAH, followed by detection of neurological function, blood-brain barrier (BBB) permeability, and brain water content. Apoptotic level of hippocampal neurons, symbolic changes of ferroptosis, and levels of pro-inflammatory cytokines were assessed using TUNEL staining, Western blotting, colorimetry, and ELISA. The localization and expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) were detected. HT22 cells were exposed to Hemin as in vitro SAH models and treated with FIN56 to induce ferroptosis, followed by evaluation of the effects of DFO on FIN56-treated HT22 cells. The regulation of Nrf2 in thioredoxin reductase 1 (TXNRD1) was analyzed by co-immunoprecipitation and Western blotting. Moreover, HT22 cells were treated with DFO and ML385 to identify the role of DFO in the Nrf2/TXNRD1 axis. DFO extenuated brain injury, and ferroptosis and inflammation in hippocampal neurons of SAH mice. Nrf2 localized at the CA1 region of hippocampal neurons, and DFO stimulated nuclear translocation of Nrf2 protein in hippocampal neurons of SAH mice. Additionally, DFO inhibited ferroptosis and inflammatory responses in FIN56-induced HT22 cells. Nrf2 positively regulated TXNRD1 protein expression. Indeed, DFO alleviated FIN56-induced ferroptosis and inflammation via activation of the Nrf2/TXNRD1 axis. DFO alleviated neurological deficits, BBB disruption, brain edema, and brain injury in mice after SAH by inhibiting hippocampal neuron ferroptosis via the Nrf2/TXNRD1 axis. DFO ameliorates SAH-induced ferroptosis and inflammatory responses in hippocampal neurons by activating the Nrf2/TXNRD1 axis.

12.
Environ Pollut ; 337: 122522, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37683760

RESUMO

Microplastics (MPs) undergo aging over time, which can influence their behavior in the environment. While laboratory-simulated studies have investigated MP aging, research on natural aging in various real environments remains limited. This study aims to investigate the physical, chemical and biological changes that occur in five types of MPs after more than 10 months of natural aging in three different real environments: seawater, air and soil. Results are compared with previous laboratory experiments. The surface roughness of all types of aged MPs was found to be higher in seawater than in air and soil, which differed from previous simulated studies that showed the highest roughness in air. All aged MPs exhibited the occurrence of hydroxyl and carbonyl groups due to the oxidation processes. Interestingly, the MPs aged in soil showed the lowest level of these functional groups, while in seawater or air, some MPs demonstrated the highest. This contrasts with previous studies indicating the highest level of oxygen-containing functional groups in aged MPs in air. Bacterial analysis identified fourteen bacterial phyla on the surface of aged MPs in all three real environments, with varying abundance in specific environments. Notably, the composition of bacterial communities in the microplastisphere was determined by the surrounding environments, independent of MP types. Natural aging is more complex than laboratory simulations, and the degree of MP aging increases with the complexity of environmental factors. These findings enhance our understanding of the natural aging of MPs in different real environments.

13.
BMJ Open ; 13(9): e074756, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37709320

RESUMO

INTRODUCTION: Sepsis is one of the most common risk factors for acute respiratory distress syndrome (ARDS). Neutrophil elastase (NE) is believed to be an important mediator of ARDS. When sepsis occurs, a large number of inflammatory factors are activated and released, which makes neutrophils migrate into the lung, eventually leading to the occurrence of ARDS. Sivelestat sodium is an NE inhibitor that can inhibit the inflammatory reaction during systemic inflammatory response syndrome and alleviate lung injury. Therefore, we hypothesise that intravenous sivelestat sodium may prevent the occurrence of ARDS in patients with sepsis. METHODS AND ANALYSIS: This is a prospective, investigator-initiated, double-blind, adaptive, multicentre, randomised, controlled clinical trial with an adaptive 'sample size re-estimation' design. Patients meeting the inclusion criteria who were transferred into the intensive care unit will be randomly assigned to receive sivelestat sodium or placebo for up to 7 days. The primary outcome is the development of ARDS within 7 days after randomisation. A total of 238 patients will be recruited based on a 15% decrease in the incidence of ARDS in the intervention group in this study. A predefined interim analysis will be performed to ensure that the calculation is reasonable after reaching 50% (120) of the planned sample size. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of ZhongDa Hospital affiliated to Southeast University (identifier: Clinical Ethical Approval No. 2021ZDSYLL153-P03). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences and meetings. TRIAL REGISTRATION NUMBER: NCT04973670.


Assuntos
Síndrome do Desconforto Respiratório , Sepse , Humanos , Estudos Prospectivos , Sepse/complicações , Sepse/prevenção & controle , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/prevenção & controle , Método Duplo-Cego , Sódio , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
14.
Artigo em Inglês | MEDLINE | ID: mdl-37758600

RESUMO

The present study aimed to investigate the association between intraoperative body temperature and prolonged length of stay (PLOS) after free flap reconstruction. A total of 753 patients who underwent head and neck surgery with free flap reconstruction were collected and randomly assigned into primary and validation cohorts. In the primary cohort, univariable and multivariable analyses were conducted to evaluate associations between intraoperative time-weighted (TW) temperature (TW average [TWA] temperature, TW hypothermia and TW hyperthermia) and PLOS. Nomograms were developed with and without intraoperative TW temperature, and validated in the validation cohort. Severe intraoperative TW hypothermia (OR = 1.004; 95% CI: 1.000, 1.007; p = 0.032) was identified as an independent risk factor for PLOS. Intraoperative TWA temperature and TW hypothermia showed linear related predictive effect for PLOS. The nomogram incorporating intraoperative TW temperature showed higher C-index (0.652, 95% CI: 0.591, 0.713) and improved net reclassification improvement for non-event (0.277, 95% CI: 0.118, 0.435; p < 0.001). Lower TWA temperature with mild TW hypothermia had a preventive effect on PLOS with a linear association, which may provide a modified range for intraoperative temperature management. The proposed nomogram incorporating intraoperative TW temperature could be used to develop personalized preventive strategies for PLOS after free flap reconstruction. IRB NUMBER: SYSEC-KY-KS-2022-037. CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

15.
Medicina (Kaunas) ; 59(9)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37763698

RESUMO

Background and Objectives: Local anesthetics administered via epidural catheters have evolved from intermittent top-ups to simultaneous administration of continuous epidural infusion (CEI) and patient-controlled epidural analgesia (PCEA) using the same device. The latest programmed intermittent epidural bolus (PIEB) model is believed to create a wider and more even distribution of analgesia inside the epidural space. The switch from CEI + PCEA to PIEB + PCEA in our department began in 2018; however, we received conflicting feedback regarding workload from the quality assurance team. This study aimed to investigate the benefits and drawbacks of this conversion, including the differences in acute pain service (APS) staff workload, maternal satisfaction, side effects, and complications before and after the changeover. Materials and Methods: Items from the APS records included total delivery time, average local anesthetic dosage, and the formerly mentioned items. The incidence of side effects, the association between the duration of delivery and total dosage, and hourly medication usage in the time subgroups of the CEI and PIEB groups were compared. The staff workload incurred from rescue bolus injection, catheter adjustment, and dosage adjustment was also analyzed. Results: The final analysis included 214 and 272 cases of CEI + PCEA and PIEB + PCEA for labor analgesia, respectively. The total amount of medication and average hourly dosage were significantly lower in the PIEB + PCEA group. The incidences of dosage change, manual bolus, extra visits per patient, and lidocaine use for rescue bolus were greater in the PIEB + PCEA group, indicating an increased staff workload. However, the two groups did not differ in CS rates, labor time, maternal satisfaction, and side effects. Conclusions: This study revealed that while PIEB + PCEA maintained the advantage of decreasing total drug doses, it inadvertently increased the staff burden. Increased workload might be a consideration in clinical settings when choosing between different methods of PCEA.

16.
Cell Mol Life Sci ; 80(10): 292, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37715829

RESUMO

Phosphatase and tensin homolog (PTEN) loss tightly correlates with prostate cancer (PCa) progression and metastasis. Inactivation of PTEN leads to abnormal activation of PI3K/AKT pathway. However, results from clinical trials with AKT inhibitors in PCa have been largely disappointing. Identification of novel regulators of PTEN in PTEN-dysfunctional PCa is urgently needed. Here we demonstrated that the expression level of PTEN is inversely correlated with the signature score of unfolded protein response (UPR) in PCa. Importantly, PTEN suppresses the activity of ATF6α, via interacting to de-phosphorylate ATF6α and consequently inhibiting its nuclear translocation. Conversely, ATF6α promotes the ubiquitination and degradation of PTEN by inducing CHIP expression. Thus, ATF6α and PTEN forms a negative feedback loop during PCa progression. Combination of ATF6α inhibitor with AKT inhibitor suppresses tumor cell proliferation and xenograft growth. Importantly, this study highlighted ATF6α as a therapeutic vulnerability in PTEN dysfunctional PCa.


Assuntos
Fosfatidilinositol 3-Quinases , Neoplasias da Próstata , Masculino , Humanos , Retroalimentação , Proteínas Proto-Oncogênicas c-akt , Neoplasias da Próstata/genética , Próstata , Inibidores da Angiogênese , Inibidores de Proteínas Quinases , PTEN Fosfo-Hidrolase/genética
17.
Front Pediatr ; 11: 1192268, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37565246

RESUMO

Objective: To investigate the clinical characteristics and outcomes of newborns infected with coronavirus disease 2019 (COVID-19) during the Omicron wave. Methods: From December 1, 2022, to January 4, 2023, clinical data were collected from neonates with COVID-19 who were admitted to 10 hospitals in Foshan City, China. Their epidemiological histories, clinical manifestations and outcomes were analysed. The neonates were divided into symptomatic and asymptomatic groups. The t test or χ2 test was used for comparisons between groups. Results: A total of 286 children were diagnosed, including 166 males, 120 females, 273 full-term infants and 13 premature infants. They were 5.5 (0-30) days old on average when they were admitted to the hospital. These children had contact with patients who tested positive for COVID-19 and were infected through horizontal transmission. This study included 33 asymptomatic and 253 symptomatic patients, among whom 143 were diagnosed with upper respiratory tract infections and 110 were diagnosed with pneumonia. There were no severe or critical patients. Fever (220 patients) was the most common clinical manifestation, with a duration of 1.1 (1-6) days. The next most common clinical manifestations were cough with nasal congestion or runny nose (4 patients), cough (34 patients), poor appetite (7 patients), shortness of breath (15 patients), and poor general status (1 patient). There were no significant abnormalities in routine blood tests among the neonates infected with COVID-19 except for mononucleosis. However, compared with the asymptomatic group, in the symptomatic group, the leukocyte and neutrophil granulocyte counts were significantly decreased, and the monocyte count was significantly increased. C-reactive protein (CRP) levels were significantly increased (≥10 mg/L) in 9 patients. Myocardial enzyme, liver function, kidney function and other tests showed no obvious abnormalities. Conclusions: In this study, neonates infected with the Omicron variant were asymptomatic or had mild disease. Symptomatic patients had lower leucocyte and neutrophil levels than asymptomatic patients.

18.
Clin Cardiol ; 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37593998

RESUMO

BACKGROUND: Cardiovascular disease (CVD) patients are more likely to have depression than general populations, and meanwhile, depression increased all-cause mortality. However, the interaction effect of depression on CVD and all-cause mortality has not been reported yet. HYPOTHESIS: Herein, we speculate that depression may play an intermediate role in the association of CVD and all-cause mortality. METHODS: Demographic and clinical data of 33,156 adults (≥20 years old) were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were used to screen the covariates and to explore the relationship of CVD and depression. Distribution-of-product method was used to assess the mediating effect of depression on the association between CVD and all-cause mortality. The mediating effect of depression was also explored in age, gender, diabetes mellitus (DM), and dyslipidemia subgroups. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs). RESULTS: Among the participants, 11 514 had CVD, 5844 had depression, and 4759 were died. After adjusting for covariates, CVD was related to high odds of depression (OR = 1.94). Depression played an intermediate role in CVD and all-cause mortality (HR = 1.23) with a mediational percentage of 9.13%. Subgroup analyses also showed this mediating effect existed in adults of different age, gender, DM and dyslipidemia status (all p < .05). CONCLUSION: The intermediate effect of depression may help clinicians to early identify high-risk populations and provide some reference for disease management and mortality reduction.

19.
Saudi Med J ; 44(8): 788-794, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37582573

RESUMO

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.


Assuntos
Doenças do Recém-Nascido , Esteroides , Vitamina K 2 , Deficiência de Vitamina K , Feminino , Humanos , Recém-Nascido , Gravidez , Corticosteroides , Cesárea , População do Leste Asiático , Recém-Nascido Pequeno para a Idade Gestacional , Estudos Retrospectivos , Fatores de Risco , Esteroides/efeitos adversos , Deficiência de Vitamina K/epidemiologia , Exposição Materna
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