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1.
J Transl Med ; 22(1): 649, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992710

RESUMO

BACKGROUND: Renal interstitial fibrosis (RIF) is a progressive, irreversible terminal kidney disease with a poor prognosis and high mortality. Angiopoietin-like 4 (ANGPTL4) is known to be associated with fibrosis in various organs, but its impact on the RIF process remains unclear. This study aimed to elucidate the role and underlying mechanisms of ANGPTL4 in the progression of RIF. METHODS: In vivo, a chronic kidney disease (CKD) rat model of renal interstitial fibrosis was established via intragastric administration of adenine at different time points (4 and 6 weeks). Blood and urine samples were collected to assess renal function and 24-h urinary protein levels. Kidney tissues were subjected to HE and Masson staining for pathological observation. Immunohistochemistry and real-time quantitative PCR (qRT‒PCR) were performed to evaluate the expression of ANGPTL4 and hypoxia-inducible factor-1α (HIF-1α), followed by Pearson correlation analysis. Subsequently, kidney biopsy tissues from 11 CKD patients (6 with RIF and 5 without RIF) were subjected to immunohistochemical staining to validate the expression of ANGPTL4. In vitro, a fibrosis model of human renal tubular epithelial cells (HK2) was established through hypoxic stimulation. Subsequently, an HIF-1α inhibitor (2-MeOE2) was used, and ANGPTL4 was manipulated using siRNA or plasmid overexpression. Changes in ANGPTL4 and fibrosis markers were analyzed through Western blotting, qRT‒PCR, and immunofluorescence. RESULTS: ANGPTL4 was significantly upregulated in the CKD rat model and was significantly positively correlated with renal injury markers, the fibrotic area, and HIF-1α. These results were confirmed by clinical samples, which showed a significant increase in the expression level of ANGPTL4 in CKD patients with RIF, which was positively correlated with HIF-1α. Further in vitro studies indicated that the expression of ANGPTL4 is regulated by HIF-1α, which in turn is subject to negative feedback regulation by ANGPTL4. Moreover, modulation of ANGPTL4 expression influences the progression of fibrosis in HK2 cells. CONCLUSION: Our findings indicate that ANGPTL4 is a key regulatory factor in renal fibrosis, forming a loop with HIF-1α, potentially serving as a novel therapeutic target for RIF.


Assuntos
Proteína 4 Semelhante a Angiopoietina , Fibrose , Subunidade alfa do Fator 1 Induzível por Hipóxia , Rim , Ratos Sprague-Dawley , Animais , Proteína 4 Semelhante a Angiopoietina/metabolismo , Proteína 4 Semelhante a Angiopoietina/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Humanos , Masculino , Rim/patologia , Rim/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Ratos , Linhagem Celular , Nefropatias/patologia , Nefropatias/metabolismo , Pessoa de Meia-Idade
2.
Nanoscale ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953142

RESUMO

Conductive bridge random access memory (CBRAM) devices exhibit great potential as the next-generation nonvolatile memory devices. However, they suffer from two major disadvantages, namely relatively high power consumption and large cycle-to-cycle and device-to-device variations, which hinder their more extensive commercialization. To learn how to enhance their device performance, kinetic Monte Carlo (KMC) simulations were employed to illustrate the variation of electroforming processes in nanomanipulated CBRAM devices by introducing an ion-blocking layer with scalable nanopores and tuning the microstructures of dielectric layers. Both the size of nanopores and the inhomogeneity of dielectric layers have significant impacts on the forming processes of conductive filaments. The dielectric layer with a high-content loose texture plus the scalable nanopore-containing ion-blocking layer leads to the formation of size-controlled and uniform filaments, which remarkably contributes to miniaturizable and stable CBRAM devices. Our study provides insights into nanomanipulation strategies to realize high-performance CBRAM devices, still awaiting future experimental confirmation.

3.
Int J Lab Hematol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960878

RESUMO

INTRODUCTION: Autologous hematopoietic stem cell transplantation (ASCT) has gained extensive application in the treatment of lymphoma and multiple myeloma (MM). Plenty of studies demonstrate that peripheral blood indicators could be considered potential predictive biomarkers for hematopoietic stem cells (HSCs) collection efficiency, including white blood cell count (WBC), monocyte count (Mono), platelet count (PLT), hematocrit, and hemoglobin levels. Currently, clinically practical predictive models based on these peripheral detection indicators to quickly, conveniently, and accurately predict collection efficiency are lacking. METHODS: In total, 139 patients with MM and lymphoma undergoing mobilization and collection of ASCT were retrospectively studied. The study endpoint was successful collection of autologous HSCs. We analyzed the effects of clinical characteristics and peripheral blood markers on collection success, and screened variables to establish a prediction model. We determined the optimal cutoff value of peripheral blood markers for predicting successful stem cell collection and the clinical value of a multi-marker prediction approach. We also established a prediction model for collection efficacy. RESULTS: Univariate and multivariate logistic regression analyses showed that the mobilization regimen, Mono, PLT, mononuclear cell count (MNC), and peripheral blood CD34+ cell count (PB CD34+ counts) were significant predictors of successful collection of peripheral blood stem cells (PBSC). Two predictive models were constructed based on the results of multivariate logistic analyses. Model 1 included the mobilization regimen, Mono, PLT, and MNC, whereas Model 2 included the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts. Receiver operating characteristic (ROC) curve analysis showed that the PB CD34+ counts, Model 1, and Model 2 could predict successful HSCs collection, with cutoff values of 26.92 × 106/L, 0.548, and 0.355, respectively. Model 1 could predict successful HSCs collection with a sensitivity of 84.62%, specificity of 75.73%, and area under the curve (AUC) of 0.863. Model 2 could predict successful HSCs collection with a sensitivity of 83.52%, specificity of 94.17%, and AUC of 0.946; thus, it was superior to the PB CD34+ counts alone. CONCLUSION: Our findings suggest that the combination of the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts before collection has predictive value for the efficacy of autologous HSCs collection in patients with MM and lymphoma. Using models based on these predictive markers may help to avoid over-collection and improve patient outcomes.

4.
Aesthetic Plast Surg ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977454

RESUMO

INDRODUCTION: The contour of the temple area can significantly influence the overall facial shape and proportions. To date, various methods and techniques have been used to augment the deficient temporal fossa; however, each of these approaches has certain inherent limitations. The present study aimed to transfer the temporoparietal fascia flap (TPFF) to the frontotemporal regions for aesthetic temporal augmentation. METHODS: This was a retrospective study of 13 cases with temporal depression who underwent a TPFF procedure for aesthetic temporal augmentation. These cases were operated for three years, from January 1, 2020, to December 1, 2023, at Nanjing Second Hospital, Nanjing, China. RESULTS: The data of bilateral temple width showed a measurement of 12.20 ± 0.53 cm (preoperative) and 14.36 ± 0.41 cm (postoperative), with a statistically significant difference (p < 0.001). There were no postoperative complications, including hematomas, infection, or facial nerve injuries. All patients were followed for 6 to 48 months (mean: 18 months) and exhibited cosmetic improvement. Overall, 10 patients were satisfied with the aesthetic results, while 3 were unsatisfied due to undercorrected depression. During the follow-up period, the temple volume was maintained. The frontal temple exhibited a smooth contour, and scalp baldness at the incision site was inconspicuous. CONCLUSIONS: Compared with other methods, the pedicled TPFF flap transfer is a safe and effective technique for correcting depressions in the frontotemporal regions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

5.
World J Psychiatry ; 14(6): 812-821, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38984333

RESUMO

BACKGROUND: Psychological problems are becoming increasingly prominent among older patients with leukemia, with patients potentially facing stigmatization after diagnosis. However, there is limited research on the stigma experienced by these patients and the factors that may contribute to it. AIM: To investigate the stigma faced by older patients after being diagnosed with leukemia and to analyze the potential influencing factors. METHODS: A retrospective analysis was conducted using clinical data obtained from questionnaire surveys, interviews, and the medical records of older patients with leukemia admitted to the Hengyang Medical School from June 2020 to June 2023. The data obtained included participants' basic demographic information, medical history, leukemia type, family history of leukemia, average monthly family income, pension, and tendency to conceal illness. The Chinese versions of the Social Impact Scale (SIS), Perceived Social Support Scale (PSSS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to assess indicators related to stigma, social support, and mental health status. We used Pearson's correlation coefficient to analyze the strength and direction of the relationship between the scores of each scale, and regression analysis to explore the factors related to the stigma of older patients with leukemia after diagnosis. RESULTS: Data from 120 patients with leukemia aged 65-80 years were analyzed. The total score on the SIS and PSSS was 43.60 ± 4.07 and 37.06 ± 2.87, respectively. The SAS score was 58.35 ± 8.32 and the SDS score was 60.58 ± 5.97. The stigma experienced by older leukemia patients was negatively correlated with social support (r = -0.691, P < 0.05) and positively correlated with anxiety and depression (r = 0.506, 0.382, P < 0.05). Age, education level, smoking status, average monthly family income, pension, and tendency to conceal illness were significantly associated with the participants' level of stigma (P < 0.05). Age, smoking status, social support, anxiety, and depression were predictive factors of stigmatization among older leukemia patients after diagnosis (all P < 0.05), with a coefficient of determination (R2) of 0.644 and an adjusted R2 of 0.607. CONCLUSION: Older patients commonly experience stigmatization after being diagnosed with leukemia. Factors such as age, smoking status, social support, and psychological well-being may influence older patients' reported experience of stigma.

6.
Angew Chem Int Ed Engl ; : e202407430, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884885

RESUMO

The Cu-glutathione (GSH) redox system, essential in biology, is designed here as a supramacromolecular assembly in which the tetrahedral 18e Cu(I) center loses a thiol ligand upon adsorption onto ZIF-8, as shown by EXAFS and DFT calculation, to generate a very robust 16e planar trigonal single-atom Cu(I) catalyst. Synergy between Cu(I) and ZIF-8, revealed by catalytic experiments and DFT, affords CO2 conversion into high-value-added chemicals with a wide scope of substrates by reaction with terminal alkynes or propargyl amines in excellent yields under mild conditions and reuse at least 10 times without significant decrease in catalytic efficiency.

7.
J Pharm Sci ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936475

RESUMO

For a pair of hydrated and anhydrous crystals, the hydrate is more stable than the anhydrate when the water activity is above the critical water activity (awc). Conventional methods to determine awc are based on either hydrate-anhydrate competitive slurries at different aw or solubilities measured at different temperatures. However, these methods are typically resource-intensive and time-consuming. Here, we present simple and complementary solution- and solid-based methods and illustrate them using carbamazepine and theophylline. In the solution-based method, awc can be predicted using intrinsic dissolution rate (IDR) ratio or solubility ratio of the hydrate-anhydrate pair measured at a known water activity. In the solid-based method, awc is predicted as a function of temperature from the dehydration temperature and enthalpy obtained by differential scanning calorimetry (DSC) near a water activity of unity. For carbamazepine and theophylline, the methods yielded awc values in good agreement with those from the conventional methods. By incorporating awc as an additional variable, the hydrate-anhydrate relationship is categorized into four classes based on their dehydration temperature (Td) and enthalpy (ΔHd) in analogy with the monotropy/enantiotropy classification for crystal polymorphs. In Class 1 (ΔHd< 0 and Td ≥ 373 K), no awc exists. In Class 2 (ΔHd>0andTd≥373K), awc always exists under conventional crystallization conditions. In Class 3 (ΔHd<0andTd<373K), awc exists when T>Td. In Class 4 (ΔHd>0andTd<373K), awc exists only when T

8.
Toxics ; 12(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38922079

RESUMO

Polyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B cells using high-throughput RNA sequencing and untargeted metabolomics technologies. The results showed that exposure to PVC-MPs significantly reduced the viability of BEAS-2B cells, leading to the differential expression of 530 genes and 3768 metabolites. Further bioinformatics analyses showed that PVC-MP exposure influenced the expression of genes associated with fluid shear stress, the MAPK and TGF-ß signaling pathways, and the levels of metabolites associated with amino acid metabolism. In particular, integrated pathway analysis showed that lipid metabolic pathways (including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism) were significantly perturbed in BEAS-2B cells following PVC-MPs exposure. This study provides new insights and targets for a deeper understanding of the toxicity mechanism of PVC-MPs and for the prevention and treatment of PVC-MP-associated lung diseases.

9.
BMC Musculoskelet Disord ; 25(1): 468, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879540

RESUMO

BACKGROUND: Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. METHODS: Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. RESULTS: After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21-7.49) in the OA cohort and 1.44 (95% CI 1.38-1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54-4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. CONCLUSIONS: OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS.


Assuntos
Síndrome do Túnel Carpal , Osteoartrite , Humanos , Síndrome do Túnel Carpal/epidemiologia , Síndrome do Túnel Carpal/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso , Incidência , Osteoartrite/epidemiologia , Osteoartrite/diagnóstico , Fatores de Risco , Bases de Dados Factuais , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/diagnóstico , Medição de Risco , Estudos Retrospectivos
11.
Biomed Pharmacother ; 176: 116904, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878686

RESUMO

Globally, cancer is a serious health problem. It is unfortunate that current anti-cancer strategies are insufficiently specific and damage the normal tissues. There's urgent need for development of new anti-cancer strategies. More recently, increasing attention has been paid to the new application of ferroptosis and nano materials in cancer research. Ferroptosis, a condition characterized by excessive reactive oxygen species-induced lipid peroxidation, as a new programmed cell death mode, exists in the process of a number of diseases, including cancers, neurodegenerative disease, cerebral hemorrhage, liver disease, and renal failure. There is growing evidence that inducing ferroptosis has proven to be an effective strategy against a variety of chemo-resistant cancer cells. Nano-drug delivery system based on nanotechnology provides a highly promising platform with the benefits of precise control of drug release and reduced toxicity and side effects. This paper reviews the latest advances of combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics. Given the new chances and challenges in this emerging area, we need more attention to the combination of nanotechnology and ferroptosis in the treatment of cancer in the future.


Assuntos
Ferroptose , Neoplasias , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Nanopartículas , Nanotecnologia/métodos , Sistemas de Liberação de Fármacos por Nanopartículas , Sistemas de Liberação de Medicamentos/métodos , Terapia Combinada , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina/métodos
12.
Cell Commun Signal ; 22(1): 337, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898461

RESUMO

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.


Assuntos
Lectinas Tipo C , Neoplasias , Receptores Imunológicos , Humanos , Receptores Imunológicos/metabolismo , Lectinas Tipo C/metabolismo , Lectinas Tipo C/antagonistas & inibidores , Animais , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Biomarcadores/metabolismo , Transdução de Sinais , Doenças Autoimunes/metabolismo , Doenças Autoimunes/imunologia , Doenças Autoimunes/tratamento farmacológico , Imunoterapia
14.
bioRxiv ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38853964

RESUMO

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD), an acute pediatric vasculitis, remains unclear. We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria, or with short-chain fatty acids (SCFAs) produced by them, attenuated cardiovascular inflammation. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from A. muciniphila , also decreased the severity of vascular inflammation. This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins acting on gut barrier function. IN BRIEF: It remains unclear whether changes in the intestinal microbiota composition are involved in the development of cardiovascular lesions associated with Kawasaki disease (KD), an immune-mediated vasculitis. Jena et al. observe alterations in the intestinal microbiota composition of mice developing vasculitis, characterized by reduced A. muciniphila and F. prausnitzii . Oral supplementation with either of these bacteria, live or pasteurized, or with bacteria-produced short-chain fatty acids (SCFAs) or Amuc_1100, the TLR-2 signaling outer membrane protein of A. muciniphila , was sufficient to alleviate the development of cardiovascular lesions in mice by promoting intestinal barrier function. HIGHLIGHTS: Absence or depletion of the microbiota decreases the severity of vasculitis in a murine model mimicking KD vasculitis. Supplementation of B. wadsworthia and B. fragilis promotes murine KD vasculitis. Decreased abundances of F. prausnitzii and A. muciniphila are associated with the development of cardiovascular lesions in mice. Supplementation with either live or pasteurized A. muciniphila and F. prausnitzii, or the TLR-2 signaling Amuc_1100, reduces the severity of vasculitis by promoting gut barrier function.

15.
JACS Au ; 4(6): 2393-2402, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38938789

RESUMO

Metal halide perovskites have outperformed conventional inorganic semiconductors in direct X-ray detection due to their ease of synthesis and intriguing photoelectric properties. However, the operational instability caused by severe ion migration under a high external electric field is still a big concern for the practical application of perovskite detectors. Here, we report a 2D (BPEA)2PbI4 (BPEA = R-1-(4-bromophenyl)ethylammonium) perovskite with Br-substituted aromatic spacer capable of introducing abundant interactions, e.g., the molecular electrostatic forces between Br atoms and aromatic rings and halogen bonds of Br-I, in the interlayer space, which effectively suppresses ion migration and thus enables superior operational stability. Constructing direct X-ray detectors based on high-quality single crystals of (BPEA)2PbI4 results in a high sensitivity of 1,003 µC Gy-1 cm-2, a low detection limit of 366 nGy s-1, and an ultralow baseline drift of 3.48 × 10-8 nA cm-1 s-1 V-1 at 80 V bias. More strikingly, it also exhibits exceptional operational stability under high flux, long-time X-ray irradiation, and large working voltage. This work shows an integration of multiple interlayer interactions to stabilize perovskite X-ray detectors, providing new insights into the future design of perovskite optoelectronic devices toward practical application.

16.
Sci Rep ; 14(1): 14942, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942771

RESUMO

A novel interval valued p,q Rung orthopair fuzzy (IVPQ-ROF) multiple attribute group decision making (MAGDM) method for sustainable supplier selection (SSS) is proposed in this paper. This study mainly contains two research points: (1) tackling the interrelation between attributes; and (2) describing the psychological state and risk attitude of decision makers (DMs). For the first research point, we introduce the Archimedean operation rules for interval valued p,q Rung orthopair fuzzy sets (IVPQ-ROFSs), then the generalized interval valued p, q Rung orthopair fuzzy Maclaurin symmetric mean (GIVPQ-ROFMSM) operator and the generalized interval valued p, q Rung orthopair fuzzy weighted Maclaurin symmetric mean (GIVPQ-ROFWMSM) operator are defined to reflect the correlation between attributes. For the second research point, we introduce the positive ideal degree (PID) and negative ideal degree (NID) based on projection of IVPQ-ROFSs, and modified regret theory. Both of them consider the best alternative and worst alternative, so as to reflect the psychological state and risk attitude of DMs. Finally, a SSS problem is presented to manifest the effectiveness of the designed method. We also provide sensitivity analysis and comparative analysis to further demonstrate the rationality and validity of the proposed method.

17.
Redox Biol ; 75: 103240, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38889621

RESUMO

T-helper 17 cells and regulatory T cells (Treg) are critical regulators in the pathogenesis of multiple sclerosis (MS) but the factors affecting Treg/Th17 balance remains largely unknown. Redox balance is crucial to maintaining immune homeostasis and reducing the severity of MS but the underlying mechanisms are unclear yet. Herein, we tested the hypothesis that peroxynitrite, a representative molecule of reactive nitrogen species (RNS), could inhibit peripheral Treg cells, disrupt Treg/Th17 balance and aggravate MS pathology by inducing nitration of interleukin-2 receptor (IL-2R) and down-regulating RAS/JNK-AP-1 signalling pathway. Experimental autoimmune encephalomyelitis (EAE) mouse model and serum samples of MS patients were used in the study. We found that the increases of 3-nitrotyrosine and IL-2R nitration in Treg cells were coincided with disease severity in the active EAE mice. Mechanistically, peroxynitrite-induced IL-2R nitration down-regulated RAS/JNK signalling pathway, subsequently impairing peripheral Treg expansion and function, increasing Teff infiltration into the central nerve system (CNS), aggravating demyelination and neurological deficits in the EAE mice. Those changes were abolished by peroxynitrite decomposition catalyst (PDC) treatment. Furthermore, transplantation of the PDC-treated-autologous Treg cells from donor EAE mice significantly decreased Th17 cells in both axillary lymph nodes and lumbar spinal cord, and ameliorated the neuropathology of the recipient EAE mice. Those results suggest that peroxynitrite could disrupt peripheral Treg/Th17 balance, and aggravate neuroinflammation and neurological deficit in active EAE/MS pathogenesis. The underlying mechanisms are related to induce the nitration of IL-2R and inhibit the RAS/JNK-AP-1 signalling pathway in Treg cells. The study highlights that targeting peroxynitrite-mediated peripheral IL-2R nitration in Treg cells could be a novel therapeutic strategy to restore Treg/Th17 balance and ameliorate MS/EAE pathogenesis. The study provides valuable insights into potential role of peripheral redox balance in maintaining CNS immune homeostasis.

18.
Eur J Protistol ; 95: 126105, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38908307

RESUMO

After Gulielmina was erected and Ophiotheca was resurrected based on some species originally included in Perichaena (Trichiaceae, Trichiales, Myxomyxetes), some specimens from the Herbarium of Fungi of Nanjing Normal University previously identified as Perichaena species were reexamined from morphological and two-gene (nuclear 18S rDNA and elongation factor-1 alpha) phylogenetic perspectives. In this study, two new myxomycete species, Gulielmina subreticulospora and Ophiotheca dictyospora, are described. Gulielmina subreticulospora shows the following character combination: branched plasmodiocarps, single peridium with circular protrusions in the inner surface, capillitium (2.4-)2.8-3.0(-3.4) µm in diameter, spores (7.4-)8.0-8.5(-9.0) µm in diameter and sub-reticulated. Ophiotheca dictyospora shows the following character combination: sessile sporocarps to short plasmodiocarps, single peridium with a densely irregular network and protrusions in the inner surface, capillitium (2.7-)3.5-5.0(-7.1) µm in diameter, uneven, decorated with spines of uneven size, spores (7.7-)8.2-8.6(-9.4) µm in diameter including obviously complete cristate reticulation with serrated edges, with deep and clear grids. Both new taxa were compared with related species and their genetic isolation was statistically tested. Moreover, a comprehensive morphological description and a detailed figure plate are provided for Perichaena verrucifera, and its phylogenetic position is determined.

19.
Int J Med Microbiol ; 315: 151621, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38759506

RESUMO

Preterm infants face a high risk of various complications, and their gut microbiota plays a pivotal role in health. Delivery modes have been reported to affect the development of gut microbiota in term infants, but its impact on preterm infants remains unclear. Here, we collected fecal samples from 30 preterm infants at five-time points within the first four weeks of life. Employing 16 S rRNA sequencing, principal coordinates analysis, the analysis of similarities, and the Wilcoxon rank-sum test, we examined the top dominant phyla and genera, the temporal changes in specific taxa abundance, and their relationship with delivery modes, such as Escherichia-Shigella and Enterococcus based on vaginal delivery and Pluralibacter related to cesarean section. Moreover, we identified particular bacteria, such as Taonella, Patulibacter, and others, whose proportions fluctuated among preterm infants born via different delivery modes at varying time points, as well as the microbiota types and functions. These results indicated the influence of delivery mode on the composition and function of the preterm infant gut microbiota. Importantly, these effects are time-dependent during the early stages of life. These insights shed light on the pivotal role of delivery mode in shaping the gut microbiota of preterm infants and have significant clinical implications for their care and management.


Assuntos
Bactérias , Parto Obstétrico , Fezes , Microbioma Gastrointestinal , Recém-Nascido Prematuro , RNA Ribossômico 16S , Humanos , Recém-Nascido , Fezes/microbiologia , Feminino , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Masculino , Gravidez , Cesárea
20.
Angew Chem Int Ed Engl ; 63(27): e202404775, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758087

RESUMO

The surface structure and chemical properties of Y-stabilized zirconia (YSZ) have been subjects of intense debate over the past three decades. However, a thorough understanding of chemical processes occurring at YSZ powders faces significant challenges due to the absence of reliable reference data acquired for well-controlled model systems. Here, we present results from polarization-resolved infrared reflection absorption spectroscopy (IRRAS) obtained for differently oriented, Y-doped ZrO2 single-crystal surfaces after exposure to CO and D2O. The IRRAS data reveal that the polar YSZ(100) surface undergoes reconstruction, characterized by an unusual, red-shifted CO band at 2132 cm-1. Density functional theory calculations allowed to relate this unexpected observation to under-coordinated Zr4+ cations in the vicinity of doping-induced O vacancies. This reconstruction leads to a strongly increased chemical reactivity and water spontaneously dissociates on YSZ(100). The latter, which is an important requirement for catalysing the water-gas-shift (WGS) reaction, is absent for YSZ(111), where only associative adsorption was observed. Together with a novel analysis Scheme these reference data allowed for an operando characterisation of YSZ powders using DRIFTS (diffuse reflectance infrared Fourier transform spectroscopy). These findings facilitate rational design and tuning of YSZ-based powder materials for catalytic applications, in particular CO oxidation and the WGS reaction.

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