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1.
Artigo em Inglês | MEDLINE | ID: mdl-38307318

RESUMO

OBJECTIVE: To investigate the parallel-forms reliability, minimal detectable change with 95% confidence interval (MDC95), and feasibility of the 4 telerehabilitation version mobility-related function scales: Fugl-Meyer Assessment-lower extremity subscale (Tele-FMA-LE), Berg Balance Scale (Tele-BBS), Tinetti Performance Oriented Mobility Assessment-Gait subscale (Tele-POMA-G), and Rivermead Mobility Index (Tele-RMI). DESIGN: Reliability and agreement study and cross-sectional study. SETTING: Medical center. PARTICIPANTS: Stroke survivors' ability to independently walk 3 meters with assistive devices, age of ≥18 years for participants and their partners, stable physical condition, and absence of cognitive impairment (N=60). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Parallel-forms reliability and MDC95 of Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI. RESULTS: No significant differences (P>.05) were observed among the mean scores of the telerehabilitation version and face-to-face version mobility-related function scales. Intraclass correlation coefficients (ICCs) indicated good reliability for most scales, with Tele-FMA-LE, Tele-BBS, and Tele-RMI scores achieving values of 0.81, 0.78, and 0.84. Tele-POMA-G scores demonstrated moderate reliability (ICC=0.72). Weighted kappa (κw) showed good-to-excellent reliability for most individual items (κw>0.60). The MDCs of the Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI were 5.84, 8.10, 2.74, and 1.31, respectively. Bland-Altman analysis showed adequate agreement between tele-assessment and face-to-face assessment for all scales. The 5 dimensions affirm the robust feasibility of tele-assessment: assessment time, subjective fatigue perception, overall preference, participant satisfaction, and system usability. CONCLUSIONS: The study demonstrates good parallel-forms reliability, MDC, and promising feasibility of the 4 telerehabilitation version mobility-related function scales (Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI) in survivors of stroke.

2.
Small ; : e2312238, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319031

RESUMO

The concentration of dopamine (DA) and tyrosine (Tyr) reflects the condition of patients with Parkinson's disease, whereas moderate paracetamol (PA) can help relieve their pain. Therefore, real-time measurements of these bioanalytes have important clinical implications for patients with Parkinson's disease. However, previous sensors suffer from either limited sensitivity or complex fabrication and integration processes. This work introduces a simple and cost-effective method to prepare high-quality, flexible titanium dioxide (TiO2 ) thin films with highly reactive (001)-facets. The as-fabricated TiO2 film supported by a carbon cloth electrode (i.e., TiO2 -CC) allows excellent electrochemical specificity and sensitivity to DA (1.390 µA µM-1  cm-2 ), Tyr (0.126 µA µM-1  cm-2 ), and PA (0.0841 µA µM-1  cm-2 ). More importantly, accurate DA concentration in varied pH conditions can be obtained by decoupling them within a single differential pulse voltammetry measurement without additional sensing units. The TiO2 -CC electrochemical sensor can be integrated into a smart diaper to detect the trace amount of DA or an integrated skin-interfaced patch with microfluidic sampling and wireless transmission units for real-time detection of the sweat Try and PA concentration. The wearable sensor based on TiO2 -CC prepared by facile manufacturing methods holds great potential in the daily health monitoring and care of patients with neurological disorders.

3.
Front Oncol ; 14: 1294253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38390261

RESUMO

Aim: Limited data are available regarding ALI's clinical relevance and prognostic value in patients with hepatocellular carcinoma (HCC) after hepatectomy. Materials and methods: HCC patients who received hepatectomy at the Meizhou People's Hospital from May 2011 to February 2022 were enrolled in the study cohort. The ALI was calculated as follows: ALI = BMI (kg/m2) × ALB (g/dL)/(absolute neutrophil count/absolute lymphocyte count). The primary outcome was overall survival (OS). The secondary outcome was cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were performed, followed by nomogram construction and decision curve analysis (DCA). Results: 425 HCC patients were enrolled for analyses. Lower preoperative ALI was significantly correlated with incomplete tumor capsule and advanced tumor stage. Lower preoperative ALI was an adverse independent prognostic factor for OS (HR: 1.512, 95% CI: 1.122-2.039, P 0.007) and CSS (HR: 1.754, 95% CI: 1.262-2.438, P <0.001) in HCC patients. The nomogram plot was built based on three (including age, TNM stage, and ALI) and two (including TNM stage and ALI) independent prognostic factors for OS and CSS, respectively. Further analyses indicated that the nomogram had better predictive value and some net benefit than the traditional TNM stage alone, especially in long-term OS. Conclusions: Our study further indicated that ALI could be a prognostic marker for OS and CSS in HCC patients after hepatectomy, especially in long-term OS.

4.
Stem Cell Res ; 76: 103352, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38394970

RESUMO

In this study, peripheral blood mononuclear cells were contributed from a male infant with propionic acidemia (PA) verified by clinical and genetic diagnosis, who inherited compound heterozygous mutations in the propionyl-CoA carboxylase subunit beta (PCCB) gene. Here, this iPS was generated by non-integrated episomal vectors with SOX2, BCL-XL, OCT4, C-MYC and OCT4. Also, this iPSC line exhibited the morphology of pluripotent stem cells, upward mRNA and protein expression of pluripotency markers, conspicuous in vitro differentiation potency and regular karyotype, and carried PCCB gene mutations, which provided an excellent model for the research and drug screening of PA.

5.
Acta Biomater ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38395101

RESUMO

Single-molecule-based synergistic phototherapy holds great potential for antimicrobial treatment. Herein, we report an orthogonal molecular cationization strategy to improve the reactive oxygen species (ROS) and hyperthermia generation of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Cationic pyridine (Py) is introduced at the meso-position of the asymmetric Cy7 with intramolecular charge transfer (ICT) to construct an atypical electron-transfer triad, which reduces ΔES1-S0, circumvents rapid charge recombination, and simultaneously enhances intersystem crossing (ISC) based on spin-orbit charge-transfer ISC (SOCT-ISC) mechanism. This unique molecular construction produces anti-Stokes luminescence (ASL) because the rotatable C-N bond enriched in high vibrational-rotational energy levels improves hot-band absorption (HBA) efficiency. The obtained triad exhibits higher singlet oxygen quantum yield and photothermal conversion efficiency compared to indocyanine green (ICG) under irradiation above 800 nm. Cationization with Py enables the triad to target bacteria via intense electrostatic attractions, as well as biocidal property against a broad spectrum of bacteria in the dark. Moreover, the triad under irradiation can enhance biofilm eradication performance in vitro and statistically improve healing efficacy of MRSA-infected wound in mice. Thus, this work provides a simple but effective strategy to design small-molecule photosensitizers for synergistic phototherapy of bacterial infections. STATEMENT OF SIGNIFICANCE: We developed an orthogonal molecular cationization strategy to enhance the reactive oxygen species and thermal effects of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Specifically, cationic pyridine (Py) was introduced at the meso-position of the asymmetric Cy7 to construct an atypical electron-transfer triad, which reduced ΔES1-S0, circumvented rapid charge recombination, and simultaneously enhanced intersystem crossing (ISC). This triad, with a rotatable C-N bond, produced anti-Stokes luminescence due to hot-band absorption. The triad enhanced antimicrobial performance and statistically improved the healing efficacy of MRSA-infected wounds in mice. This site-specific cationization strategy may provide insights into the design of small molecule-based photosensitizers for synergistic phototherapy of bacterial infections.

6.
J Hazard Mater ; 469: 133898, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38422737

RESUMO

The growing prevalence of lithium (Li) batteries has drawn public attention to Li as an emerging pollutant. The present study investigates the toxicity of Li+ on Chromochloris zofingiensis, examining physiological, biochemical and omics aspects. Results reveal hormesis effects of Li+ on C. zofingiensis growth. At Li+ concentrations below 5 mg L-1, Li+ can enhance chlorophyll content, mitochondrial activity, and antioxidant capacity, leading to increased dry cell weight and cell number. Conversely, when it exceeded 10 mg L-1, Li+ can reduce chlorophyll content, induce oxidative stress, and disrupt chloroplast and mitochondria structure and function, ultimately impeding cell growth. In addition, under 50 mg L-1 Li+ stress, microalgae optimize absorbed light energy use (increasing Fv/Fm and E TR ) and respond to stress by up-regulating genes in starch and lipid biosynthesis pathways, promoting the accumulation of storage components. Weighted gene co-expression network analysis indicates that peptidylprolyl cis/trans isomerase, GTPase and L-ascorbate oxidase might be the key regulators in response to Li+ stress. This research marks the toxic effects and molecular mechanisms of Li+ on freshwater microalga, which would improve our understanding of Li's toxicology and contributing to the establishment of Li pollution standards.

7.
Talanta ; 272: 125780, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38359722

RESUMO

Mercury ion (Hg2+) poses a serious threat to human health due to its high toxicity. In this study, a smartphone-based photoelectrochemical sensor based on oxygen vacancies (OVs) driven signal enhancement for mercury ion detection was designed. BiVO4-x/Bi2S3/AuNPs were combined with T-Hg2+-T recognition mode to construct a multi-sandwich photoelectrochemical sensor. On the one hand, the OVs can increase the adsorption of light by the materials and enhance the photocurrent response as well as the superconductivity of Au NPs to accelerate the charge transfer at the electrode interface. On the other hand, the multi-sandwich structure was exploited to increase the binding site of Hg2+, as well as the T-Hg2+-T structure for sensitive recognition of Hg2+ and signal amplification. The sensor showed good linearity for Hg2+ concentration in the range of 0.1 nM-1.0 µM with a detection limit of 4.8 pM (S/N = 3). Eventually the smartphone-based real-time detection sensor is expected to contribute to the future analysis of heavy metal ions.

8.
Ther Adv Cardiovasc Dis ; 18: 17539447241232774, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415471

RESUMO

BACKGROUND: Evidence regarding the relationship between dietary calcium intake and severe abdominal aortic calcification (AAC) is limited. Therefore, this study aimed to investigate the association between dietary calcium intake and severe AAC in American adults based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The present cross-sectional study utilized data from the NHANES 2013-2014, a population-based dataset. Dietary calcium intake was assessed using two 24-h dietary recall interviews. Quantification of the AAC scores was accomplished utilizing the Kauppila score system, whereby severe AAC was defined as having an AAC score greater than 6. We used multivariable logistic regression models, a restricted cubic spline analysis, and a two-piecewise linear regression model to show the effect of calcium intake on severe AAC. RESULTS: Out of the 2640 individuals examined, 10.9% had severe AAC. Following the adjustment for confounding variables, an independent association was discovered between an augmented intake of dietary calcium and the incidence of severe AAC. When comparing individuals in the second quartile (Q2) of dietary calcium intake with those in the lowest quartile (Q1), a decrease in the occurrence of severe AAC was observed (odds ratio: 0.66; 95% confidence interval: 0.44-0.99). Furthermore, the relationship between dietary calcium intake and severe AAC demonstrated an L-shaped pattern, with an inflection point observed at 907.259 mg/day. Subgroup analyses revealed no significant interaction effects. CONCLUSION: The study revealed that the relationship between dietary calcium intake and severe AAC in American adults is L-shaped, with an inflection point of 907.259 mg/day. Further research is required to confirm this association.


Assuntos
Aorta Abdominal , Formas L , Adulto , Humanos , Aorta Abdominal/diagnóstico por imagem , Cálcio da Dieta , Estudos Transversais , Inquéritos Nutricionais
9.
J Hematol Oncol ; 17(1): 7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302992

RESUMO

BACKGROUND: While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N6-methyladenosine (m6A) methyltransferase, in HCC development/maintenance, CSC stemness, as well as normal hepatogenesis. METHODS: Liver-specific Mettl16 conditional KO (cKO) mice were generated to assess its role in HCC pathogenesis and normal hepatogenesis. Hydrodynamic tail-vein injection (HDTVi)-induced de novo hepatocarcinogenesis and xenograft models were utilized to determine the role of METTL16 in HCC initiation and progression. A limiting dilution assay was utilized to evaluate CSC frequency. Functionally essential targets were revealed via integrative analysis of multi-omics data, including RNA-seq, RNA immunoprecipitation (RIP)-seq, and ribosome profiling. RESULTS: METTL16 is highly expressed in liver CSCs and its depletion dramatically decreased CSC frequency in vitro and in vivo. Mettl16 KO significantly attenuated HCC initiation and progression, yet only slightly influenced normal hepatogenesis. Mechanistic studies, including high-throughput sequencing, unveiled METTL16 as a key regulator of ribosomal RNA (rRNA) maturation and mRNA translation and identified eukaryotic translation initiation factor 3 subunit a (eIF3a) transcript as a bona-fide target of METTL16 in HCC. In addition, the functionally essential regions of METTL16 were revealed by CRISPR gene tiling scan, which will pave the way for the development of potential inhibitor(s). CONCLUSIONS: Our findings highlight the crucial oncogenic role of METTL16 in promoting HCC pathogenesis and enhancing liver CSC self-renewal through augmenting mRNA translation efficiency.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células-Tronco Neoplásicas , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Autorrenovação Celular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metiltransferases/genética , Metiltransferases/metabolismo , Células-Tronco Neoplásicas/patologia , Biossíntese de Proteínas , Ribossomos/metabolismo , RNA
10.
Cell Signal ; 117: 111088, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38316267

RESUMO

BACKGROUND AND OBJECTIVE: Hypertensive nephropathy is the second leading cause of end-stage renal disease, but its underlying pathogenesis remains unclear. Therefore, this study aimed to explore whether transmembrane protein 16 A (TMEM16A), the molecular basis of calcium-activated chloride channels (CaCC), is involved in the development and progression of hypertensive nephropathy. METHODS: In vivo and in vitro experiments were conducted using a hypertensive murine model and human kidney proximal tubular epithelial cells (HK-2 cells), respectively. EXPERIMENTAL RESULTS: The expression of TMEM16A was down-regulated in renal samples of hypertensive nephropathy patients and hypertensive model mice, accompanied by excessive deposition of extracellular matrix proteins (ECM) such as Fibronectin, Laminin, Collagen I and Collagen III, the up-regulation of α-smooth muscle actin (α-SMA) expression, and the decrease of E-cadherin. Overexpression of TMEM16A or knockdown of TMEM16A inhibited or promoted the expression of Wnt/ß-catenin signaling pathway proteins Wnt3a, LRP5 and active ß-catenin in HK-2 cells, preventing the epithelial-to-mesenchymal transition (EMT) of renal tubules, and the synthesis of ECM components. CONCLUSION: In angiotensin II (Ang II)-induced hypertensive nephropathy, TMEM16A was identified as a key player inhibiting the detrimental changes in renal tubules, suggesting a potential avenue for mitigating renal damage in hypertensive nephropathy.

11.
Medicine (Baltimore) ; 103(7): e37141, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363890

RESUMO

BACKGROUND: Myxoma is a common type of primary cardiac tumor. However, there are few researches to illustrate challenge of safely inducing anesthesia in a patient with a giant right atrial myxoma at moderate altitude. PATIENT CONCERNS AND DIAGNOSES: A 54-year-old female patient lived in a city with an average altitude of 1932 m with scheduled surgical treatment for giant right atrial myxoma, prompting discussions on appropriate anesthesia modalities given her prolonged residence at moderate altitude. METHODS AND RESULTS: Considering the potential impact of moderate altitude on perioperative management, this study emphasizes the necessity of adequate volume preload therapy and the utility of transthoracic echocardiography or transesophageal echocardiography to prevent hemodynamic compromise. Furthermore, it highlights the unique consideration that, post-tumor removal, hypotension may not necessarily lead to decreased oxygen saturation in these patients. CONCLUSION: This case underscores the importance of avoiding hypotension, as pre-tumor resection blood pressure maintenance primarily determines blood oxygen concentration. Additionally, it sheds light on the intriguing observation that post-tumor removal hypotension may not result in decreased oxygen saturation. These findings have significant implications for the perioperative care of patients with giant right atrial myxoma at moderate altitudes.


Assuntos
Anestésicos , Neoplasias Cardíacas , Hipotensão , Mixoma , Humanos , Feminino , Pessoa de Meia-Idade , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Mixoma/complicações , Mixoma/diagnóstico por imagem , Mixoma/cirurgia , Hipotensão/etiologia
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(1): 66-73, 2024 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-38318898

RESUMO

OBJECTIVE: To evaluate the postoperative denture restoration and denture function in patients with mandibular defect reconstructed with vascularized free fibula flap. METHODS: In the study, 154 patients who underwent mandibular segment resection and used vascularized free fibula flap to repair mandibular defects due to inflammation, trauma and tumor from January 2015 to December 2020 were collected. These patients had common inclusion criteria which were stable occlusal relationship before operation, segmental defects of mandibular bone caused by lesions of mandible and adjacent parts (such as floor of mouth, tongue, cheek), free fibula flap used for repair and surviving after operation. Relevant data were reviewed and situation of denture restoration was followed up. A questionnaire related to denture functional evaluation had been proposed for those who had completed the denture rehabilitation. The evaluation index of denture restoration function was assigned by expert authority to obtain the denture function score. SPSS 18.0 software was used for statistical analysis of the basic information of the patients included in the study and the denture restoration of the patients. RESULTS: The rate of postoperative denture restoration in the patients with mandibular defects repaired by free fibula flap was 17.5%, and the rate of postoperative denture restoration in the patients with benign mandibular tumors was 25.0% (18/72), which was significantly greater than that in the patients with malignant tumors 11.0% (9/82, P < 0.05). There was no significant difference in denture function score between the patients with condylar defect and those without condylar defect in denture repair rate and denture function score (P>0.05). The functional score of implant denture was significantly greater than that of removable denture (P < 0.05). According to Brown classification, the denture function score of the patients with the defect invo-lving the anterior mandibular region was significantly greater than that of the patients without the anterior mandibular region involved (P < 0.05). The poor oral conditions, such as less amount of remaining teeth, insufficient retention strength, large mobility of soft tissue in the surgical area, poor oral vestibular groove condition became the main reason of not receiving denture restoration (37.86%). CONCLUSION: The denture rehabilitation of mandibular defect reconstructed with vascularized free fibula flap is closely rela-ted to pathological properties and oral conditions. The clinical outcome of implant denture has been confirmed effectively and it is a better choice for future denture restoration after mandibular reconstruction.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Fíbula/cirurgia , Transplante Ósseo , Mandíbula/cirurgia , Retalhos de Tecido Biológico/cirurgia , Dentaduras
13.
ACS Biomater Sci Eng ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373308

RESUMO

Respiratory signals are critical clinical diagnostic criteria for respiratory diseases and health conditions, and respiratory sensors play a crucial role in achieving the desired respiratory monitoring effect. High sensitivity to a single factor can improve the reliability of respiratory monitoring, and maintaining the hygiene of the sensors is also important for daily health monitoring. Herein, we propose a flexible Au-modified anatase titanium dioxide resistive respiratory sensor, which can be mechanically compliantly attached to curved surfaces for respiratory monitoring in different modalities (i.e., respiratory intensity, frequency, and rate). The uniform and preferentially oriented anatase titanium dioxide films gained by the polymer-assisted deposition technique can be fabricated on flexible substrates through a liquid-assisted transferring process. The Au modification can enhance surface plasmon resonance to facilitate the photocatalytic activity of titanium dioxide, and the optimized distribution of Au on the surface of titanium dioxide film made the sensor have an excellent antibacterial effect. The uniquely designed encapsulation can effectively control the contact between the surface of titanium dioxide films and electrodes, allowing the flexible sensor to exhibit fast response time (0.71 s) and recovery time (1.06 s) to respiratory as well as insensitivity or low sensitivity to other factors (i.e., gas composition, humidity, temperature, stress, and strain). This work provided an effective strategy for flexible wearable respiratory sensors and has great potential in daily respiratory monitoring for health management and pandemic control.

14.
Sci Total Environ ; : 171201, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38417506

RESUMO

Mycelial pellets formed by Penicillium thomii ZJJ were applied as efficient biosorbents for the removal of polycyclic aromatic hydrocarbons (PAHs), which are a type of ubiquitous harmful hydrophobic pollutants. The live mycelial pellets were able to remove 93.48 % of pyrene at a concentration of 100 mg/L within 48 h, demonstrating a maximum adsorption capacity of 285.63 mg/g. Meanwhile, the heat-killed one also achieved a removal rate of 65.01 %. Among the six typical PAHs (pyrene, phenanthrene, fluorene, anthracene, fluoranthene, benzo[a]pyrene), the mycelial pellets preferentially adsorbed the high molecular weight PAHs, which also have higher toxicity, resulting in higher removal efficiency. The experimental results showed that the biosorption of mycelial pellets was mainly a spontaneous physical adsorption process that occurred as a monolayer on a homogeneous surface, with mass transfer being the key rate-limiting step. The main adsorption sites on the surface of mycelia were carboxyl and N-containing groups. Extracellular polymeric substances (EPS) produced by mycelial pellets could enhance adsorption, and its coupling with dead mycelia could achieve basically the same removal effect to that of living one. It can be concluded that biosorption by mycelial pellets occurred due to the influence of electrostatic and hydrophobic interactions, consisting of five steps. Furthermore, the potential applicability of mycelial pellets has been investigated considering diverse factors. The mycelia showed high environmental tolerance, which could effectively remove pyrene across a wide range of pH and salt concentration. And pellets diameters and humic acid concentration had a significant effect on microbial adsorption effect. Based on a cost-effectiveness analysis, mycelium pellets were found to be a low-cost adsorbent. The research outcomes facilitate a thorough comprehension of the adsorption process of pyrene by mycelial pellets and their relevant applications, proposing a cost-effective method without potential environmental issues (heat-killed mycelial pellets plus EPS) to removal PAHs.

15.
FASEB J ; 38(2): e23443, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38265281

RESUMO

Immune-mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin-28A (IL-28A), a member of the IL-10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL-28A, its role in immune-mediated acute injury remains unclear. The present study investigated the role of IL-28A in concanavalin A (Con A)-induced acute immune liver injury. After Con A injection in mice, IL-28A level significantly increased. IL-28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL-28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL-28A-deficiency group than in the wild-type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL-28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-12, IL-6, and IL-1ß, by M1 macrophages decreased significantly in the IL-28A-deficiency group. Western blotting demonstrated that IL-28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL-28A deletion plays an important protective role in the Con A-induced acute liver injury model and IL-28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF-κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune-related hepatic injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Citocinas , Interferon lambda , Interleucinas , Animais , Camundongos , Concanavalina A , Fatores Reguladores de Interferon , Fígado , Macrófagos , Proteínas Quinases Ativadas por Mitógeno , Interferon lambda/genética , Interleucinas/genética
16.
Cancer Res ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38190709

RESUMO

Overweight and obesity are identified by a high body mass index (BMI) and carry significant health risks due to associated co-morbidities. Although epidemiological data connects overweight/obesity with 13 cancer types, a better understanding of the molecular mechanisms underlying this correlation are needed to improve prevention and treatment strategies. In this study, we conducted a comprehensive analysis of molecular differences between overweight or obese patients and normal-weight patients across 14 different cancer types from The Cancer Genome Atlas (TCGA). Using the propensity score weighting algorithm to control for confounding factors, obesity-specific mutational features were identified, such as higher mutation burden in rectal cancer and biased mutational signatures in other cancers. Differentially expressed genes (DEGs) in tumors from patients with overweight/obesity were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of elevated body fat on gene expression profiles and clinical outcomes in cancer patients. Interestingly, while high BMI seemed to have a negative impact on most cancer types, the normal weight biased mutational and gene expression patterns indicated overweight/obesity may be beneficial in endometrial cancer, suggesting the presence of an "obesity paradox" in this context. Body fat also significantly impacted the tumor microenvironment by modulating immune cell infiltration, underscoring the importance of understanding the interplay between weight and immune response in cancer progression. Together, this study systematically elucidates the molecular differences corresponding to body weight in multiple cancer types, offering potentially critical insights for developing precision therapy for cancer patients.

17.
J Mol Neurosci ; 74(1): 12, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236354

RESUMO

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a broad spectrum of symptoms and prognoses. Effective therapy requires understanding this variability. ASD children's cognitive and immunological development may depend on iron homoeostasis. This study employs a machine learning model that focuses on iron metabolism hub genes to identify ASD subgroups and describe immune infiltration patterns. A total of 97 control and 148 ASD samples were obtained from the GEO database. Differentially expressed genes (DEGs) and an iron metabolism gene collection achieved the intersection of 25 genes. Unsupervised cluster analysis determined molecular subgroups in individuals with ASD based on 25 genes related to iron metabolism. We assessed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, gene set variation analysis (GSVA), and immune infiltration analysis to compare iron metabolism subtype effects. We employed machine learning to identify subtype-predicting hub genes and utilized both training and validation sets to assess gene subtype prediction accuracy. ASD can be classified into two iron-metabolizing molecular clusters. Metabolic enrichment pathways differed between clusters. Immune infiltration showed that clusters differed immunologically. Cluster 2 had better immunological scores and more immune cells, indicating a stronger immune response. Machine learning screening identified SELENBP1 and CAND1 as important genes in ASD's iron metabolism signaling pathway. These genes express in the brain and have AUC values over 0.8, implying significant predictive power. The present study introduces iron metabolism signaling pathway indicators to predict ASD subtypes. ASD is linked to immune cell infiltration and iron metabolism disorders.


Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/genética , Homeostase , Encéfalo , Bases de Dados Factuais , Ferro
18.
ACS Nano ; 18(2): 1582-1598, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38170456

RESUMO

Heterogeneity of the tumor microenvironment (TME) is primarily responsible for ineffective tumor treatment and uncontrolled tumor progression. Pyroptosis-based immunogenic cell death (ICD) therapy is an ideal strategy to overcome TME heterogeneity and obtain a satisfactory antitumor effect. However, the efficiency of current pyroptosis therapeutics, which mainly depends on a single endogenous or exogenous stimulus, is limited by the intrinsic pathological features of malignant cells. Thus, it is necessary to develop a synergistic strategy with a high tumor specificity and modulability. Herein, a synergistic nanoplatform is constructed by combining a neutrophil camouflaging shell and a self-synergistic reactive oxygen species (ROS) supplier-loaded polymer. The covered neutrophil membranes endow the nanoplatform with stealthy properties and facilitate sufficient tumor accumulation. Under laser irradiation, the photosensitizer (indocyanine green) exogenously triggers ROS generation and converts the laser irradiation into heat to upregulate NAD(P)H:quinone oxidoreductase 1, which further catalyzes ß-Lapachone to self-produce sufficient endogenous ROS, resulting in amplified ICD outcomes. The results confirm that the continuously amplified ROS production not only eliminates the primary tumor but also concurrently enhances gasdermin E-mediated pyroptosis, initiates an ICD cascade, re-educates the heterogeneous TME, and promotes a systemic immune response to suppress distant tumors. Overall, this self-synergistic nanoplatform provides an efficient and durable method for redesigning the immune system for targeted tumor inhibition.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Morte Celular Imunogênica , Piroptose , Espécies Reativas de Oxigênio , Temperatura Alta , Linhagem Celular Tumoral , Microambiente Tumoral
19.
Ecotoxicol Environ Saf ; 270: 115922, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171106

RESUMO

Bisphenol A (BPA), an environmental endocrine disruptor (EDC), has been implicated in impairing intestinal and male reproductive dysfunction. The efficacy of gut microbiota modulation for BPA-exposed testicular dysfunction has yet to be verified through research. Therefore, this study explored the potential of mixed probiotics in restoring spermatogenesis damage through the gut-testis axis under BPA exposure. We selected two probiotics strains (Lactobacillus rhamnosus and Lactobacillus plantarum) with BPA removal properties in vitro and the BPA-exposed male mice model was established. The probiotics mixture effectively reduced BPA residue in the gut, serum, and testis in mice. Through 16 S rDNA-seq and metabolomics sequencing, we uncovered that vitamin D metabolism and bile acid levels in the gut was abolished under BPA exposure. This perturbation was linked to an increased abundance of Faecalibaculum and decreased abundance of Lachnospiraceae_NK4A136_group and Ligilactobacillus. The probiotics mixture restored this balance, enhancing intestinal barrier function and reducing oxidative stress. This improvement was accompanied by a restored balance of short-chain fatty acids (SCFAs). Remarkably, the probiotics ameliorated testicular dysfunction by repairing structures of seminiferous tubules and reversing arrested spermiogenesis. Further, the probiotics mixture enhanced testosterone-driven increases in spermatogonial stem cells and all stages of sperm cells. Testicular transcriptome profiling linked these improvements to fatty acid degradation and peroxisome pathways. These findings suggest a significant interplay between spermatogenesis and gut microbiota, demonstrating that probiotic intake could be a viable strategy for combating male subfertility issues caused by BPA exposure.


Assuntos
Microbioma Gastrointestinal , Fenóis , Probióticos , Masculino , Camundongos , Animais , Sêmen , Espermatogênese , Compostos Benzidrílicos/toxicidade , Probióticos/farmacologia
20.
Sci Rep ; 14(1): 2553, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297089

RESUMO

The outbreak of the epidemic in 2020 has caused a huge negative impact on the production and operation of firms, directly threatening their survival and development. However, some firms can make timely and effective adjustments in the face of sudden crises because of their resilience, and then turn the corner. This study selects the data of 2993 companies listed in Chinese A shares. The OLS method and event study is used to analyze the impact of ESG on the ability of corporate system crisis (corporate resilience). The research results indicate that companies with good ESG performance are more resilient in crises. The mechanism test indicates that the easing effect of corporate financing constraints and the expansion effect of corporate green innovation capabilities are important channels for ESG performance to promote the negative impact of crisis shocks on corporate value. Heterogeneity analysis indicates that ESG has a stronger ability to respond to systemic crises in small-scale firms, state-owned firms, and highly competitive market environments. Powerful CEOs can weaken ESG's ability to respond to systemic corporate crises. Further research has found that only S and G items, namely good governance level and social performance, have a significant positive promoting effect on corporate resilience. ESG performance may be more important in areas more severely affected by the epidemic. This study expands the research on ESG and the research on the decision mechanism of enterprise resilience. This study provides a new theoretical perspective for the study of corporate crisis response capabilities, and provides a certain policy reference for Chinese firms to effectively respond to public crises, which has important policy implications.

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