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1.
Acta Biomater ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38561074

RESUMO

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

2.
Heliyon ; 10(7): e28958, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601655

RESUMO

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

4.
Food Chem ; 450: 139376, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38648695

RESUMO

Wuyi Rock Tea (WRT) has different characteristics of "rock flavor" due to different production areas. In this study, we investigated the flavor characteristics and key components of "rock flavor" and the influence of microorganisms on the substances by combining metabolomics and microbiomics with the Rougui WRTs from the Zhengyan, Banyan, and Waishan production areas. The results showed that Rougui has a strong floral and fruity aroma, which is mainly brought by hotrienol, and the sweet, smooth, and fresh taste is composed of epicatechin gallate, epigallocatechin, epigallocatechin gallate, caffeine, theanine, soluble sugar, and sweet and bitter amino acids. Bacteria Chryseobacterium, Pedobacter, Bosea, Agrobacterium, Stenotrophomonas, and Actinoplanes mainly influence the production of hotrienol, epicatechin gallate, and theanine. Fungi Pestalotiopsis, Fusarium, Elsinoe, Teichospora and Tetracladium mainly influence the production of non-volatile compounds. This study provides a reference for the biological formation mechanism of the characteristic aroma of WRT's "rock falvor".

5.
Acta Paediatr ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501583

RESUMO

AIM: This study aimed to classify quiet sleep, active sleep and wake states in preterm infants by analysing cardiorespiratory signals obtained from routine patient monitors. METHODS: We studied eight preterm infants, with an average postmenstrual age of 32.3 ± 2.4 weeks, in a neonatal intensive care unit in the Netherlands. Electrocardiography and chest impedance respiratory signals were recorded. After filtering and R-peak detection, cardiorespiratory features and motion and cardiorespiratory interaction features were extracted, based on previous research. An extremely randomised trees algorithm was used for classification and performance was evaluated using leave-one-patient-out cross-validation and Cohen's kappa coefficient. RESULTS: A sleep expert annotated 4731 30-second epochs (39.4 h) and active sleep, quiet sleep and wake accounted for 73.3%, 12.6% and 14.1% respectively. Using all features, and the extremely randomised trees algorithm, the binary discrimination between active and quiet sleep was better than between other states. Incorporating motion and cardiorespiratory interaction features improved the classification of all sleep states (kappa 0.38 ± 0.09) than analyses without these features (kappa 0.31 ± 0.11). CONCLUSION: Cardiorespiratory interactions contributed to detecting quiet sleep and motion features contributed to detecting wake states. This combination improved the automated classifications of sleep states.

6.
Insects ; 15(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38535339

RESUMO

Plutella xylostella, a destructive crucifer pest, can rapidly develop resistance to most classes of pesticides. This study investigated the molecular resistance mechanisms to chlorpyrifos, an organophosphate pesticide. Two P. xylostella genes, ace1 and ace2, were described. The nucleotide sequence results revealed no variation in ace2, while the resistant strain (Kar-R) had four amino acid alterations in ace1, two of which (A298S and G324A) were previously shown to confer organophosphate resistance in P. xylostella. In the present study, the 3D model structures of both the wild-type (Gu-S) and mutant (Kar-R) of P. xylostella ace1 strains were studied through molecular dynamics (MDs) simulations and molecular docking. Molecular dynamics simulations of RMSD revealed less structural deviation in the ace1 mutant than in its wild-type counterpart. Higher flexibility in the 425-440 amino acid region in the mutant active site (Glu422 and Acyl pocket) increased the active site's entropy, reducing the enzyme's affinity for the inhibitors. Gene expression analysis revealed that the relative transcription levels of ace1 were significantly different in the Kar-R strain compared with the Gu-S strain. This study enhances the understanding of the mechanisms governing ace1's resistance to insecticide and provides essential insights for new insecticides as well as valuable insights into environmentally conscious pest management techniques.

7.
Virology ; 594: 110050, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479071

RESUMO

The SARS-CoV-2 Omicron variant, which was classified as a variant of concern (VOC) by the World Health Organization on 26 November 2021, has attracted worldwide attention for its high transmissibility and immune evasion ability. The existing COVID-19 vaccine has been shown to be less effective in preventing Omicron variant infection and symptomatic infection, which brings new challenges to vaccine development and application. Here, we evaluated the immunogenicity and safety of an Omicron variant COVID-19 inactivated vaccine containing aluminum and CpG adjuvants in a variety of animal models. The results showed that the vaccine candidate could induce high levels of neutralizing antibodies against the Omicron variant virus and binding antibodies, and significantly promoted cellular immune response. Meanwhile, the vaccine candidate was safe. Therefore, it provided more foundation for the development of aluminum and CpG as a combination adjuvant in human vaccines.


Assuntos
Compostos de Alúmen , Vacinas contra COVID-19 , COVID-19 , Animais , Humanos , Alumínio , SARS-CoV-2 , COVID-19/prevenção & controle , Adjuvantes Imunológicos , Imunidade Celular , Anticorpos Neutralizantes , Vacinas de Produtos Inativados , Anticorpos Antivirais
8.
J Psychiatr Res ; 173: 139-150, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531144

RESUMO

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.


Assuntos
Microbioma Gastrointestinal , Pessoa de Meia-Idade , Camundongos , Humanos , Feminino , Animais , Lactente , Microbioma Gastrointestinal/genética , Fezes/microbiologia , Depressão/terapia , Depressão/metabolismo , Camundongos Endogâmicos C57BL , Transplante de Microbiota Fecal , RNA Ribossômico 16S/genética
9.
Inorg Chem ; 63(14): 6418-6426, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38526055

RESUMO

Direct photocatalytic hydrogen from earth-abundant seawater is a great potential way to achieve sustainable and clean energy, yet unsatisfactory decomposition and rapid electron-hole pair recombination of catalysts hinder the solar-driven H2 conversion efficiency. Herein, we designed a series of PtCu alloy nanoparticle-modified porous triptycene-based polymers (PtxCu1-TCP) to construct the heterostructure for highly efficient hydrogen generation from photocatalytic water/seawater splitting. Characterizations displayed that TCP with an ultrahigh surface area can confine the agglomeration of PtCu alloy; meanwhile, the PtCu alloy can facilitate the rapid electron transfer from TCP. In addition, TCP with a stable covalent bond structure can resist the corrosion of seawater. Benefiting from these two advantages, Pt7Cu1-TCP showed a remarkably enhanced photocatalytic performance with a maximum H2 evolution rate of 3255 µmol g-1 h-1 in natural seawater with triethanolamine, which is 2.69, 116.25, and 1.08 times that of Pt-TCP, Cu-TCP, and optimal catalyst in pure water, respectively. This study provides an idea for the development of a novel catalytic system for hydrogen production from solar-driven water/seawater splitting.

10.
Free Radic Biol Med ; 215: 79-93, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38447853

RESUMO

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS: Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS: Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION: Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.


Assuntos
Ferroptose , Fármacos Neuroprotetores , Hemorragia Subaracnóidea , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais , Doenças Neuroinflamatórias , Hidrogênio/farmacologia
11.
Free Radic Biol Med ; 214: 173-183, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342163

RESUMO

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.


Assuntos
Lesões Encefálicas , Fluorocarbonos , Hipóxia Encefálica , Hemorragia Subaracnóidea , Animais , Humanos , Oxigênio , Fluorocarbonos/uso terapêutico , Hipóxia Encefálica/terapia
12.
Brain Behav ; 14(2): e3399, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38340139

RESUMO

OBJECTIVE: To explore the impact of inflammatory factors on the incidence of cerebral small vessel disease (CSVD), we performed a mendelian randomization (MR) study to analyze the causal relationship between multiple inflammatory factors and CSVD imaging markers and utilized summary-data-based mendelian randomization (SMR) analysis to infer whether the impact of instrumental variables (IVs) on disease is mediated by gene expression or DNA methylation. METHODS: Using public databases such as UKB and IEU, and original genome-wide association studies, we obtained IVs related to exposure (inflammatory factors) and outcome (CSVD imaging markers). We performed the inverse variance weighted, weighted median, and MR-Egger methods to assess causal effects between exposure and outcome in univariate MR analysis. To evaluate their heterogeneity, a series of sensitivity analyses were conducted, including the Cochrane Q test, MR-Egger intercept test, MR-Presso, and leave-one-out analysis. We also applied mediation and multivariate MR analysis to explore the interactions between positive exposures on the same outcome. Additionally, we conducted the SMR, which utilizes instruments within or near relevant genes in blood or brain tissues, to elucidate the causal associations with CSVD markers. RESULTS: ABO Univariate MR of multiple cohorts revealed that the risk of small vessel stroke (SVS) increases with elevated levels of TNF-related apoptosis-inducing ligand (TRAIL, OR, 1.23, 95% CI, 1.08-1.39) and interleukin-1 receptor-like 2, (IL-1RL2, OR, 1.29, 95% CI, 1.04-1.61). IL-18 was a potential risk factor for extensive basal ganglia perivascular space burden (BGPVS, OR, 1.02, 95% CI, 1.00-1.05). Moreover, the risk of extensive white matter perivascular space burden (WMPVS) decreased with rising levels of E-selectin (OR, .98, 95% CI, .97-1.00), IL-1RL2 (OR, .97, 95% CI, .95-1.00), IL-3 receptor subunit alpha (IL-3Ra, OR, .98, 95% CI, .97-1.00), and IL-5 receptor subunit alpha (IL-5Ra, OR, .98, 95% CI, .97-1.00). Mediation and multivariate MR analysis indicated that E-selectin and IL-3Ra might interact during the pathogenesis of WMPVS. SMR estimates showed that TRAIL-related IVs rs5030044 and rs2304456 increased the risk of SVS by increasing the expression of gene Kininogen-1 (KNG1) in the cerebral cortex, particularly in the frontal cortex (ßsmr = .10, Psmr = .003, FDR = .04). Instruments (rs507666 and rs2519093) related to E-selectin and IL-3Ra could increase the risk of WMPVS by enhancing DNA methylation of the gene ABO in blood tissue (ßsmr = .01-.02, Psmr = .001, FDR = .01-.03). CONCLUSION: According to MR and SMR analysis, higher levels of TRAIL increased the risk of SVS by upregulating gene expression of KNG1 in brain cortex tissues. In addition, protective effects of E-selectin and IL-3a levels on WMPVS were regulated by increased DNA methylation of gene ABO in blood tissue.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Selectina E , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fatores de Risco , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/genética
13.
Physiol Meas ; 45(2)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38271714

RESUMO

Objective. Monitoring of apnea of prematurity, performed in neonatal intensive care units by detecting central apneas (CAs) in the respiratory traces, is characterized by a high number of false alarms. A two-step approach consisting of a threshold-based apneic event detection algorithm followed by a machine learning model was recently presented in literature aiming to improve CA detection. However, since this is characterized by high complexity and low precision, we developed a new direct approach that only consists of a detection model based on machine learning directly working with multichannel signals.Approach. The dataset used in this study consisted of 48 h of ECG, chest impedance and peripheral oxygen saturation extracted from 10 premature infants. CAs were labeled by two clinical experts. 47 features were extracted from time series using 30 s moving windows with an overlap of 5 s and evaluated in sets of 4 consecutive moving windows, in a similar way to what was indicated for the two-step approach. An undersampling method was used to reduce imbalance in the training set while aiming at increasing precision. A detection model using logistic regression with elastic net penalty and leave-one-patient-out cross-validation was then tested on the full dataset.Main results. This detection model returned a mean area under the receiver operating characteristic curve value equal to 0.86 and, after the selection of a FPR equal to 0.1 and the use of smoothing, an increased precision (0.50 versus 0.42) at the expense of a decrease in recall (0.70 versus 0.78) compared to the two-step approach around suspected apneic events.Significance. The new direct approach guaranteed correct detections for more than 81% of CAs with lengthL≥ 20 s, which are considered among the most threatening apneic events for premature infants. These results require additional verifications using more extensive datasets but could lead to promising applications in clinical practice.


Assuntos
Apneia do Sono Tipo Central , Recém-Nascido , Lactente , Humanos , Apneia do Sono Tipo Central/diagnóstico , Recém-Nascido Prematuro , Apneia/diagnóstico , Algoritmos
14.
Food Chem ; 443: 138542, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38281414

RESUMO

Shuixian is renowned for its "rock flavor". However, the variations in Shuixian flavor are unclear, as the discussion mainly considers regional factors and overlooks the role of microorganisms. Sensory evaluation of Shuixian from three different regions (Zhengyan, Banyan, and Waishan) revealed that each had unique flavor characteristics: a woody aroma with slight acidity, a strong floral and fruity aroma with good freshness, and a distinct sweet aroma and sourness. Metabolomic analyses have revealed that 2-methylpyrazine was a crucial component of the woody aroma, whereas other metabolites contributed to sweet aroma, freshness, and acidity. Moreover, examinations of the relationship between flavor metabolites and microorganisms revealed that fungi had a more pronounced influence on the metabolite content of Shuixian. The study evaluated the role of fermentation microorganisms in shaping the flavor based on Shuixian flavor analyses, contributing to further research into the "rock flavor", as well as potential microbial interventions.


Assuntos
Camellia sinensis , Camellia sinensis/metabolismo , Odorantes/análise , Metabolômica , Fermentação , Chá/metabolismo
15.
Angew Chem Int Ed Engl ; 63(11): e202400323, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38247990

RESUMO

Metal-organic frameworks (MOFs) have emerged as promising oxygen evolution reaction (OER) electrocatalysts. Chemically bonded MOFs on supports are desirable yet lacking in routine synthesis, as they may allow variable structural evolution and the underlying structure-activity relationship to be disclosed. Herein, direct MOF synthesis is achieved by an organic acid-etching strategy (AES). Using π-conjugated ferrocene (Fc) dicarboxylic acid as the etching agent and organic ligand, a series of MFc-MOF (M=Ni, Co, Fe, Zn) nanosheets are synthesized on the metal supports. The crystal structure is studied using X-ray diffraction and low-dose transmission electron microscopy, which is quasi-lattice-matched with that of the metal, enabling in situ MOF growth. Operando Raman and attenuated total reflectance Fourier transform infrared spectroscopy disclose that the NiFc-MOF features dynamic structural rebuilding during OER. The reconstructed one showing optimized electronic structures with an upshifted total d-band center, high M-O bonding state occupancy, and localized electrons on adsorbates indicated by density functional theory calculations, exhibits outstanding OER performance with a fairly low overpotential (130 mV at 10 mA cm-2 ) and good stability (144 h). The newly established approach for direct MOF synthesis and structural reconstruction disclosure stimulate the development of more prudent catalysts for advancing OER.

16.
Heliyon ; 10(1): e23167, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169774

RESUMO

Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B, a major component of selectivity factor 1 (SL1), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B, in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.

17.
Free Radic Biol Med ; 210: 416-429, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042225

RESUMO

BACKGROUND: Menaquinone-4(MK-4), the isoform of vitamin K2 in the brain, exerts neuroprotective effects against a variety of central nervous system disorders. This study aimed to demonstrate the anti-ferroptosis effects of MK-4 in neurons after SAH. METHODS: A subarachnoid hemorrhage (SAH) model was prepared by endovascular perforation in mice. In vitro hemoglobin stimulation of primary cortical neurons mimicked SAH. MK-4, Brequinar (BQR, DHODH inhibitor), and Selisistat (SEL, SIRT1 inhibitor) were administered, respectively. Subsequently, WB, immunofluorescence was used to determine protein expression and localization, and transmission electron microscopy was used to observe neuronal mitochondrial structure while other indicators of ferroptosis were measured. RESULTS: MK-4 treatment significantly upregulated the protein levels of DHODH; decreased GSH, PTGS2, NOX1, ROS, and restored mitochondrial membrane potential. Meanwhile, MK-4 upregulated the expression of SIRT1 and promoted its entry into the nucleus. BQR or SEL partially abolished the protective effect of MK-4 on, neurologic function, and ferroptosis. CONCLUSIONS: Taken together, our results suggest that MK-4 attenuates ferroptosis after SAH by upregulating DHODH through the activation of SIRT1.


Assuntos
Lesões Encefálicas , Ferroptose , Hemorragia Subaracnóidea , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Di-Hidro-Orotato Desidrogenase , Vitamina K 2/farmacologia , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Lesões Encefálicas/metabolismo
18.
Pest Manag Sci ; 80(3): 1533-1546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37964702

RESUMO

BACKGROUND: Spodoptera frugiperda, a global agricultural pest, can be effectively controlled through the sterile insect technique. However, exposure to low-dose radiation below the sterilization threshold may induce hormetic effects. Here, the biphasic aspects of the fertile progeny population of S. frugiperda were analyzed using an age-stage, two-sex life table after dosing male and female pupae with 10-350 Gy gamma radiation. RESULTS: The parental sterilizing dose for 6-day-old female and male pupae was 200 and 350 Gy, respectively. The total longevity, pre-adult survival rate, net reproduction rate, and intrinsic growth rate of the offspring population increased with decreasing radiation doses from 250 to 10 Gy. Offspring population of parents treated with low doses of 10-100 Gy showed better life table parameters compared to non-irradiated controls. Females and males fecundity irradiated with 10, 50, and 100 Gy and 10 Gy, respectively, exceeded controls, producing 2339.4, 2726.4, 2311, and 2369 eggs, as opposed to 1802.9 eggs produced by the controls. Males irradiated with 10 Gy displayed the highest intrinsic rates of increase and net reproduction rate, at 0.1709 and 682.3, respectively. Projections from the survival rate and fecundity indicated that female and male S. frugiperda populations after 10 Gy irradiation may grow considerably faster than the controls. CONCLUSION: This study explores the hormetic effects of low-dose radiation on S. frugiperda through life table analysis, while providing enhancements for utilizing substerilizing gamma dose in a modified F1 sterility technique. © 2023 Society of Chemical Industry.


Assuntos
Infertilidade , Mariposas , Animais , Masculino , Feminino , Spodoptera , Tábuas de Vida , Fertilidade
19.
Curr Protein Pept Sci ; 25(1): 71-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37642183

RESUMO

BACKGROUND: Recently, the importance of the interactions between liver cancer cells and fibroblasts has been increasingly recognized; however, many details remain to be explored. METHODS: In this work, we first studied their intercellular interactions using conditioned medium from mouse embryonic fibroblasts (MEFs), then through a previously established coculture model. RESULTS: Culturing in a conditioned medium from MEFs could significantly increase the growth, migration, and invasion of liver cancer cells. The coculture model further demonstrated that a positive feedback loop was formed between transforming growth factor-ß (TGF-ß) from HepG2 cells and mHGF (mouse hepatocyte growth factor) from MEFs during coculture. In this feedback loop, c-Met expression in HepG2 cells was significantly increased, and its downstream signaling pathways, such as Src/FAK, PI3K/AKT, and RAF/MEK/ERK, were activated. Moreover, the proportion of activated MEFs was also increased. More importantly, the growth-promoting effects caused by the interaction of these two cell types were validated in vitro by a 3D spheroid growth assay and in vivo by a xenograft mouse model. CONCLUSION: Collectively, these findings provide valuable insights into the interactions between fibroblasts and liver cancer cells, which may have therapeutic implications for the treatment of liver cancer.


Assuntos
Neoplasias Hepáticas , Fator de Crescimento Transformador beta , Humanos , Animais , Camundongos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Xenoenxertos , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fibroblastos/metabolismo , Modelos Animais de Doenças , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo
20.
Lymphat Res Biol ; 22(1): 60-65, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37787968

RESUMO

Objective: The purpose of this study is to investigate the effect of complete decongestive therapy (CDT), based on fluoroscopy-guided manual lymph drainage (FG-MLD), combined with intermittent pneumatic compression (IPC) on patients with secondary bilateral lower limb lymphedema after comprehensive treatment for gynecological malignant tumors. Methods: After comprehensive treatment for gynecological malignant tumors, 18 patients suffering from bilateral lower limb lymphedema were evaluated and treated by specialist nurses (with the qualification of lymphedema therapists). The treatment course included manual drainage, IPC, bandaging, functional exercise, and skincare etc., which are performed once a day for a total of 18 times. Results: After performing the treatment 18 times, a significant reduction is observed in the patient's bilateral lower limb circumference, extracellular water (ECW) content, and lower limb segment ECW ratio. Moreover, the 50-kHz bioelectrical impedance and quality of life (QoL) scores are found to be significantly higher than before treatment (all p < 0.05). Subjective symptoms also improve significantly (p < 0.05), except for local swelling (p = 0.289 > 0.05). Conclusions: CDT based on FG-MLD, combined with IPC, effectively relieves secondary bilateral lower limb lymphedema after comprehensive treatment of gynecological malignant tumors. It also improves subjective symptoms and patients' QoL, thus deserving clinical reference and promotion.


Assuntos
Linfedema , Neoplasias , Humanos , Qualidade de Vida , Linfedema/diagnóstico , Linfedema/etiologia , Linfedema/terapia , Drenagem , Extremidade Inferior , Resultado do Tratamento
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