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1.
Biochem Biophys Res Commun ; 717: 150061, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38718570

RESUMO

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.


Assuntos
Apigenina , Transição Epitelial-Mesenquimal , Glucose , Histonas , Epitélio Pigmentado da Retina , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Animais , Apigenina/farmacologia , Acetilação/efeitos dos fármacos , Humanos , Glucose/metabolismo , Glucose/toxicidade , Histonas/metabolismo , Linhagem Celular , Camundongos , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Camundongos Endogâmicos C57BL , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/tratamento farmacológico , Proteína p300 Associada a E1A/metabolismo , Masculino , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Proteína de Ligação a CREB/metabolismo , Proteína de Ligação a CREB/genética
2.
Int Immunopharmacol ; 135: 112223, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772295

RESUMO

Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.

3.
Sci Rep ; 14(1): 10735, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730029

RESUMO

The humidity has often been measured through a single point sensor. Where, the humidity could be varied at different locations as well as depending on environmental conditions. The present paper developed the dual point humidity measuring sensor by using a polymer optical fiber (POF) based on a single illuminating fiber. The sensor's basic structure is to twist two fibers and bend them at a certain radius. However, the dual point sensor is developed through the cascading of twisted micro bend (TMB-1 and TMB-2). The twisting of fibers couples the light from one fiber to another fiber through the side coupling method. An increase in the humidity level leads to a change in the reflective index, which helps to get variation in coupled light intensity. To measure the humidity, the dual point sensors are placed into the control humidity chamber at two random positions. The power reading variation is significantly linear when the humidity level increases from 30 to 80%. The sensor has a fast response of about 1 s and a recovery time of about 4 s. Furthermore, the chemical coating is applied to improve the sensor's sensitivity. Between 30 and 80% range of humidity, the both sensors of dual point TMB-1 and TMB-2 have appropriate sensitivity and detection limits, which is about 680.8 nW/% and 763.9 nW/% and 1.37% and 1.98%, respectively. To measure the humidity at variable positions, the present dual points humidity sensor is well-stable, easy, and straightforward, which uses a less expensive method.

4.
Clin Otolaryngol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622816

RESUMO

INTRODUCTION: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). METHODS: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. RESULTS: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. CONCLUSION: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC.

5.
Acad Radiol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599906

RESUMO

RATIONALE AND OBJECTIVES: To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). METHODS: A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. RESULTS: 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. CONCLUSION: The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

6.
J Neuroinflammation ; 21(1): 111, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685040

RESUMO

BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.


Assuntos
Becaplermina , Dieta Hiperlipídica , Células Endoteliais , Hipocampo , Síndrome Metabólica , Microglia , Transcitose , Animais , Camundongos , Becaplermina/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Transcitose/fisiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Microglia/metabolismo , Microglia/patologia , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Masculino , Osso e Ossos/metabolismo , Osso e Ossos/patologia
7.
Biomed Rep ; 20(5): 71, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38544962

RESUMO

Although chronic osteomyelitis (COM) affecting the extremities is a frequently occurring disease, the incidence of squamous cell carcinoma (SCC) arising from COM is rare. Consequently, understanding the diagnosis, treatment and prognosis of such a disorder remains limited. In the present study, a case of COM-associated SCC was demonstrated. A 65-year-old woman arrived to the Southern Medical University Nanfang Hospital (Guangzhou, China) with multiple sinus tracts and skin ulcers in the distal part of her left thigh, persisting for over 50 years following an open pierce injury by an ox horn. A local biopsy confirmed the diagnosis of COM-related SCC. Although limb amputation was recommended, the female patient declined initially. Instead, the female patient underwent focused debridement and wide resection of the tumor, followed by local implantation of calcium sulfate beads loaded with vancomycin and gentamycin, and application of a rail fixator. A total of 10 months later, the cancer recurred, affecting the osseous tissue. Subsequently, the patient underwent amputation of the thigh. At the one-year follow-up, the patient showed satisfactory recovery without signs of local recurrence. Despite its rarity, the severity of this disorder should not be underestimated. Personalized treatment strategies must be tailored to individual circumstances.

8.
Soft Matter ; 20(12): 2812-2822, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38446214

RESUMO

The droplet lossless directional motion control on slippery surfaces holds immense promise for applications in microfluidic chips, hazardous substance detection, chemical dispensing, etc. However, a significant challenge in this domain lies in efficiently developing soft, slippery surfaces with large-range anisotropic wettability and compatibility for curved scenarios. This study addressed this challenge through a quick 3D printing-assisted method to produce soft, ridged-slippery surfaces (SRSSs) as the droplet manipulation platform. The SRSSs demonstrated substantial anisotropic rolling resistances, measuring 116.9 µN in the perpendicular direction and 7.7 µN in the parallel direction, exhibiting a ratio of 15.2. Combining several extents of anisotropic wettability on a soft substrate could realize diverse reagent manipulation functions. Furthermore, these SRSSs showcased high compatibility with various droplet constituents, impressive liquid impact resistance, self-repair capability, and mechanical durability and thermal durability, ensuring exceptional applicability. As proofs of concept, the SRSSs were successfully applied in droplet control and classification for heavy metal ion detection, mechanical arm-based droplet grab and release, and cross-species transport, showcasing their remarkable versatility, compatibility, and practicality in advanced droplet microfluidic chips and water harvesting applications.

9.
J Exp Clin Cancer Res ; 43(1): 46, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342894

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) poses a significant health burden in specific regions of Asia, and some of NPC patients have bone metastases at the time of initial diagnosis. Bone metastasis can cause pathologic fractures and pain, reducing patients' quality of life, and is associated with worse survival. This study aims to unravel the complex role of insulin-like growth factor 1 receptor (IGF-1R) in NPC bone metastasis, offering insights into potential therapeutic targets. METHODS: We assessed IGF-1R expression in NPC cells and explored its correlation with bone metastasis. Experiments investigated the impact of osteoclast-secreted IGF-1 on the IGF-1R/AKT/S6 pathway in promoting NPC cell proliferation within the bone marrow. Additionally, the reciprocal influence of tumor-secreted Granulocyte-macrophage colony-stimulating factor (GM-CSF) on osteoclast differentiation and bone resorption was examined. The effects of IGF-1 neutralizing antibody, IGF-1R specific inhibitor (NVP-AEW541) and mTORC inhibitor (rapamycin) on nasopharyngeal carcinoma bone metastasis were also explored in animal experiments. RESULTS: Elevated IGF-1R expression in NPC cells correlated with an increased tendency for bone metastasis. IGF-1, secreted by osteoclasts, activated the IGF-1R/AKT/S6 pathway, promoting NPC cell proliferation in the bone marrow. Tumor-secreted GM-CSF further stimulated osteoclast differentiation, exacerbating bone resorption. The IGF-1 neutralizing antibody, NVP-AEW541 and rapamycin were respectively effective in slowing down the rate of bone metastasis and reducing bone destruction. CONCLUSION: The intricate interplay among IGF-1R, IGF-1, and GM-CSF highlights potential therapeutic targets for precise control of NPC bone metastasis, providing valuable insights for developing targeted interventions.


Assuntos
Neoplasias Ósseas , Reabsorção Óssea , Neoplasias Nasofaríngeas , Animais , Humanos , Carcinoma Nasofaríngeo/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/uso terapêutico , Osteoclastos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Qualidade de Vida , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/patologia , Sirolimo/farmacologia , Anticorpos Neutralizantes
10.
Environ Res ; 247: 118167, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38262514

RESUMO

Sewage sludge incineration ash (SSIA) is rich in phosphorus (P), thus being considered as a reliable source of phosphorus recovery. Different P species behaved significant bioavailability. Based on this, a comprehensive investigation into the bioavailability transition path of P species during sewage sludge (SS) incineration was conducted. P predominantly existed in the form of inorganic phosphorus (IP) in SS with a higher concentration of non-apatite inorganic phosphorus (NAIP) and less concentration of apatite inorganic phosphorus (AP). During the SS incineration process, OP existed in the flocs and cell structures of SS underwent destruction, the released P then combined with metal elements such as Ca, Mg, Fe, and Al to form AP species (Ca/Mg-P) and NAIP species (Fe/Al/Mn-P), and the NAIP decomposition to release into gas phase. This was the initial step for enhancing the bioavailability of P species. As temperature increased and the incineration process progressed, the low-temperature-resistant NAIP dissociated, and the metal-binding sites of Al, Fe and Mn in NAIP species were gradually replaced by the Ca and Mg thus forming thermal stability AP species (Ca/Mg-P, such as CaHPO4, Ca2PO4Cl, and Mg3(PO4)2 et al.). This step was crucial for the bioavailability improvement of P species during the incineration process. Therefore, the IP proportions in TP were extremely high (>98%), and this value gradually increased as incineration temperature raised. The higher incineration temperature, the lower NAIP concentration and higher AP concentration. Besides, additives such as coal/rice husk/eggshell played a significant affect. Additives wither higher Ca content were inclined to react with P to form Ca/Mg-P (AP), while the presence of SO2 would react with Ca metals to form CaSO4 thus inhibiting the formation of AP species (such as CaHPO4 and CaPO4Cl). This results could provide theoretical support for the efficient and directional migration of P during sewage sludge incineration.


Assuntos
Fósforo , Esgotos , Disponibilidade Biológica , Incineração , Temperatura Alta
11.
Sci Total Environ ; 914: 169856, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190916

RESUMO

Waste polyethylene terephthalate (PET) with high carbon content (>60 wt%) has shown great potential in the field of synthesizing carbon materials for CO2 capture, attracting increasing attention. Herein, an innovative strategy was proposed to synthesize nitrogen-doped hierarchical porous carbon (PC) for CO2 capture using PET as precursor and sodium amide (NaNH2) as both nitrogen dopant and low-temperature activator. As-synthesized N-doped PC exhibited a significantly high micropore volume of 0.755 cm3/g and a rich content of N- and O-containing functional groups, offering ample active sites for CO2 molecules. Further, the adsorbents demonstrated excellent CO2 capture capacity, achieving 5.7 mmol/g (0 °C) and 3.3 mmol/g (25 °C) at 1 bar, respectively. This was primarily attributed to the synergistic effect of narrow micropores filling and electrostatic interactions. Moreover, as-synthesized PC exhibited rapid CO2 adsorption capability, and its dynamic adsorption process was effectively described using a pseudo-second-order kinetic model. After five consecutive cycles, PET-derived PC still maintained ~100 % of adsorption capacity. They also possessed good CO2/N2 selectivity and reasonable isosteric heat of adsorption. Therefore, as-synthesized nitrogen-doped PC is a promising CO2 adsorbent through low-temperature activation of carbonized PET with NaNH2. Such findings have substantial implications for waste plastic recycling and mitigating the greenhouse effect.

12.
Risk Manag Healthc Policy ; 17: 29-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38196919

RESUMO

Objective: This study aimed to assess the utility of chromosomal microarray analysis (CMA) and noninvasive prenatal testing (NIPT) in detecting clinically significant chromosomal abnormalities among fetuses presenting ultrasonic soft markers (USMs). Methods: A retrospective observational study, spanning from January 1, 2019, to September 30, 2022, enrolled 539 singleton pregnant women with fetal USMs at our center. Of these, 418 cases (77.6%) underwent NIPT, while 121 cases (22.4%) opted for invasive prenatal diagnosis post-appropriate genetic counseling. Cases with high-risk NIPT results proceeded to invasive prenatal diagnosis, where conventional karyotyping and CMA were concurrently performed. Further stratification was done based on the number of USMs, classifying cases into single-USM and multiple-USM groups. Results: Of the 24 cases (4.5%) exhibiting abnormal findings, 17 presented numerical chromosomal abnormalities, 2 featured clinically significant copy number variations (CNVs), 3 showed variants of unknown significance (VOUS), 1 displayed LOH, and 1 exhibited chromosome nine inversion. Notably, 18 cases (75%) theoretically detectable by karyotyping (eg, sizes above 10Mb) and 16 cases (66.7%) detectable by NIPT for five common aneuploidies were identified. Six submicroscopic findings (25%) were exclusively detectable by CMA. The predominant clinically relevant aberrations were observed in the thickened nuchal-translucency (TNT) group (9/35, 25.7%), followed by the multiple soft markers group (3/32, 9.3%). In the NIPT group, the false positive rate was 1.22%, and the false negative rate was 0%. Conclusion: The prevalence of chromosome aneuploidy exceeded that of submicroscopic chromosomal imbalance in pregnant women with fetal USMs. NIPT demonstrated efficacy, particularly for soft markers like echogenic intracardiac focus. However, for those with TNT and multiple soft markers, invasive prenatal diagnosis, including CMA testing, is recommended as the primary investigative approach.

13.
J Pineal Res ; 76(1): e12914, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37753741

RESUMO

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.


Assuntos
Melatonina , Osteomielite , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Osteoblastos , Osteogênese , Staphylococcus aureus , Osteomielite/tratamento farmacológico
14.
Proc Natl Acad Sci U S A ; 121(1): e2310685120, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38147550

RESUMO

Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.


Assuntos
Leptina , Ossificação Heterotópica , Animais , Camundongos , Leptina/genética , Ligantes , Camundongos Endogâmicos C57BL , Osteogênese , Receptores para Leptina/genética , Receptores para Leptina/metabolismo
15.
Aging Cell ; 23(3): e14072, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38126583

RESUMO

Osteoporosis and its related fractures are common causes of morbidity and mortality in older adults, but its underlying molecular and cellular mechanisms remain largely unknown. In this study, we found that lipoteichoic acid (LTA) treatment could ameliorate age-related bone degeneration and attenuate intramedullary macrophage senescence. FOXO1 signaling, which was downregulated and deactivated in aging macrophages, played a key role in the process. Blocking FOXO1 signaling caused decreased REDD1 expression and increased phosphorylation level of mTOR, a major driver of aging, as well as aggravated bone loss and deteriorated macrophage senescence. Moreover, LTA elevated FOXO1 signaling through ß-catenin pathway while ß-catenin inhibition significantly suppressed FOXO1 signaling, promoted senescence-related protein expression, and accelerated bone degeneration and macrophage senescence. Our findings indicated that ß-catenin/FOXO1/REDD1 signaling plays a physiologically significant role that protecting macrophages from senescence during aging.


Assuntos
Lipopolissacarídeos , Osteoporose , Ácidos Teicoicos , beta Catenina , Humanos , Idoso , beta Catenina/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , Senescência Celular , Via de Sinalização Wnt , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo
16.
J Hazard Mater ; 464: 132999, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-37988945

RESUMO

Mercury ions (Hg2+) primarily target mitochondria in the cells. Therefore, the development of novel probes that specifically target mitochondria in the presence of Hg2+ is of immense importance. Most previously reported probes that utilize the softness of S, Te, O, and/or N atoms for Hg2+ binding often face problems such as fluorescence quenching and off-target signals. In this study, bromide-hydrocarbon pyridinium salts were designed to target the mitochondria and chelate Hg2+ via Hg-Br coordination bonds. As a prototype, four aggregation-induced emission (AIE) fluorogens, namely TPP-Br, TPP-Cl, R1, and R2, with a similar D-π-A structure but slight differences in their halogen substituents, were designed. Among them, only TPP-Br achieved the highly selective and sensitive detection of Hg2+ by triggering its AIE properties, resulting in remarkable emission enhancement (80-fold), colorimetry, and the Tyndall effect. TPP-Br exhibited high selectivity and sensitivity to Hg2+ with a detection limit of 0.35 µM, rapid response time (<10 s), and large Stokes shift of 185 nm. Their interaction modes were studied using a combination of 1H nuclear magnetic resonance spectroscopy, scanning electron microscopy, fluorescent lifetime decay, and theoretical calculations. TPP-Br exhibited a low emission background in cells, whereas in the presence of Hg2+, mitochondria were lit up with wash-free staining. This study provides a powerful tool for accurately diagnosing mercury poisoning-related diseases in mitochondria.


Assuntos
Corantes Fluorescentes , Mercúrio , Corantes Fluorescentes/química , Brometos , Mitocôndrias , Coloração e Rotulagem , Espectrometria de Fluorescência/métodos
17.
Cells ; 12(22)2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37998339

RESUMO

E. coli is a ubiquitous pathogen that is responsible for over one million fatalities worldwide on an annual basis. In animals, E. coli can cause a variety of diseases, including mastitis in dairy cattle, which represents a potential public health hazard. However, the pathophysiology of E. coli remains unclear. We found that E. coli could induce global upregulation of m6A methylation and cause serious apoptosis in bovine mammary epithelial cells (MAC-T cells). Furthermore, numerous m6A-modified lncRNAs were identified through MeRIP-seq. Interestingly, we found that the expression of LOC4191 with hypomethylation increased in MAC-T cells upon E. coli-induced apoptosis. Knocking down LOC4191 promoted E. coli-induced apoptosis and ROS levels through the caspase 3-PARP pathway. Meanwhile, knocking down ALKBH5 resulted in the promotion of apoptosis through upregulated ROS and arrested the cell cycle in MAC-T cells. ALKBH5 silencing accelerated LOC4191 decay by upregulating its m6A modification level, and the process was recognized by hnRNP A1. Therefore, this indicates that ALKBH5 stabilizes m6A-modified LOC4191 to suppress E. coli-induced apoptosis. This report discusses an initial investigation into the mechanism of m6A-modified lncRNA in cells under E. coli-induced apoptosis and provides novel insights into infectious diseases.


Assuntos
Apoptose , Escherichia coli , Feminino , Animais , Bovinos , Escherichia coli/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/genética , Metilação de DNA
18.
Appl Opt ; 62(17): 4474-4481, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37707139

RESUMO

In this paper, temperature compensation of plastic optical fiber (POF) is studied and gold absorbability is utilized. Gold film is modified on the surface of POF by magnetron sputtering. The temperature output characteristics of different structures such as ordinary (POF-N), side-polished (POF-SP), U-shaped (POF-U), and narrow groove structure (POF-NGS) are tested, and the effects of gold film thickness, polishing area, and sputtering sequence on the temperature output characteristics are also investigated. The power change of the sensor at different temperatures is recorded. The experimental results show that when the temperature is between 25°C and 50°C and the sputtering gold film thickness is 50 nm, the temperature stabilities of POF-N, POF-U, POF-SP, and POF-NGS are 1.02 µW/°C, 0.77 µW/°C, 0.18 µW/°C, and 0.35 µW/°C, respectively. The compensation effect is enhanced as the gold film thickness increases. When the thickness is 100 nm, the temperature stability of POF-NGS is 0.06 µW/°C. The proposed temperature compensation method is competitive and straightforward.

19.
Stem Cell Res Ther ; 14(1): 230, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649087

RESUMO

Inflammation is the host's protective response against harmful external stimulation that helps tissue repair and remodeling. However, excessive inflammation seriously threatens the patient's life. Due to anti-inflammatory effects, corticosteroids, immunosuppressants, and monoclonal antibodies are used to treat various inflammatory diseases, but drug resistance, non-responsiveness, and severe side effect limit their development and application. Therefore, developing other alternative therapies has become essential in anti-inflammatory therapy. In recent years, the in-depth study of stem cells has made them a promising alternative drug for the treatment of inflammatory diseases, and the function of stem cells is regulated by a variety of signals, of which dopamine signaling is one of the main influencing factors. In this review, we review the effects of dopamine on various adult stem cells (neural stem cells, mesenchymal stromal cells, hematopoietic stem cells, and cancer stem cells) and their signaling pathways, as well as the application of some critical dopamine receptor agonists/antagonists. Besides, we also review the role of various adult stem cells in inflammatory diseases and discuss the potential anti-inflammation function of dopamine receptors, which provides a new therapeutic target for regenerative medicine in inflammatory diseases.


Assuntos
Células-Tronco Adultas , Células-Tronco Mesenquimais , Células-Tronco Neurais , Adulto , Humanos , Dopamina , Células-Tronco Hematopoéticas , Inflamação/terapia
20.
Acta Biomater ; 169: 209-227, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37516419

RESUMO

At present, surgical debridement and systematic administration of antibiotics represent the mainstay of treatment for chronic osteomyelitis. However, it is now understood that Staphylococcus aureus (S. aureus) can survive within excessively polarized M2 macrophages and evade antibiotics, accounting for the high recurrence of chronic osteomyelitis. Effective treatments for intracellular infection have rarely been reported. Herein, we designed an in situ sprayed liposomes hydrogels spray with macrophage-targeted effects and the ability to reverse polarization and eradicate intracellular bacteria to reduce the recurrence of osteomyelitis. Resiquimod (R848)-loaded and phosphatidylserine (PS)-coating nanoliposomes were introduced into fibrinogen and thrombin to form the PSL-R848@Fibrin spray. Characterization and phagocytosis experiments were performed to confirm the successful preparation of the PSL-R848@Fibrin spray. Meanwhile, in vitro cell experiments validated its ability to eliminate intracellular S. aureus by reprogramming macrophages from the M2 to the M1 phenotype. Additionally, we established a chronic osteomyelitis rat model to simulate the treatment and recurrence process. Histological analysis demonstrated a significant increase in M1 macrophages and the elimination of intracellular bacteria. Imaging revealed a significant decrease in osteomyelitis recurrence. Overall, the liposome hydrogels could target macrophages to promote antibacterial properties against intracellular infection and reduce the recurrence of chronic osteomyelitis, providing the foothold for improving the outcomes of this patient population. STATEMENT OF SIGNIFICANCE: Chronic osteomyelitis remains a high recurrence although undergoing traditional treatment of debridement and antibiotics. S. aureus can survive within the excessively polarized M2 macrophages to evade the effects of antibiotics. However, few studies have sought to investigate effective intracellular bacteria eradication. Herein, we designed a macrophage-targeted R848-containing liposomes fibrin hydrogels spray (PSL-R848@Fibrin) that can reprogram polarization of macrophages and eradicate intracellular bacteria for osteomyelitis treatment. With great properties of rapid gelation, strong adhesion, high flexibility and fit-to-shape capacity, the facile-operated immunotherapeutic in-situ-spray fibrin hydrogels exhibited huge promise of reversing polarization and fighting intracellular infections. Importantly, we revealed a hitherto undocumented treatment strategy for reducing the recurrence of chronic osteomyelitis and potentially improving the prognosis of chronic osteomyelitis patients.


Assuntos
Osteomielite , Infecções Estafilocócicas , Humanos , Ratos , Animais , Lipossomos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Staphylococcus aureus , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fibrina/farmacologia
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