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2.
J Oleo Sci ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35034940

RESUMO

Obesity is occurring due to continue taken high fat diet; this is the fast-growing problem reaching epidemic proportion globally. Ursolic acid altered the abnormal glucose metabolism in diabetic rats. In this experimental protocol, we examine ursolic acid (UA) anti-obesity effect against streptozotocin (STZ) and high-fat diet-induced obesity in rats. Orally administered the ursolic acid (2.5, 5 and 10 mg/kg) dose to the hyperglycemic rats for 8 weeks and estimated the blood glucose level at different time intervals. Biochemical, hepatic, lipid, renal and antioxidant parameters were estimated. Traf-4, Mapk-8, Traf-6 and genes such as Ins-1, ngn-3 and Pdx-1 mRNA expression were estimated using qRT-PCR to scrutinize the molecular mechanism in MAPK downstream JNK cascade and insulin pathway signalling pathways. Ursolic acid significantly (p<0.001) down-regulated the blood glucose level at dose dependent manner. Its also reduced the plasma insulin level, non-essential fatty acid and increased the level of adiponectin as compared to obese control group rats. Ursolic acid treated group rats reduced the level of total cholesterol and triglycerides. Ursolic-acid-treated rats have been shown to decrease oxidative stress in pancreatic tissue by restoring the free radical effect of scavenging, suppress the Traf-6, Mapk-8 and Traf-4 mRNA expression, enhance the expression of Pdx-1, Ins-1 and Ngn-3 and ensure the regeneration of pancreas ß cells and therefore pancreas insulin. The current result suggested the anti-obese effect of ursolic acid against high fat diet (HFD) induced obese rats via alteration of insulin and JNK signaling pathway.

3.
Exp Ther Med ; 23(2): 139, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35069820

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosion of articular cartilage and bone and has adverse effects on both patients and livestock animals. The aim of the present study was to investigate the role of interleukin-1ß (IL-1ß) in the pathogenesis of RA, and to further determine whether injection of IL-1ß small interfering RNA (siRNA) or transplantation of IL-1ß siRNA + bone marrow mesenchymal stem cells (BMSCs) can ameliorate RA in rats. A collagen-induced arthritis (CIA) rat model was established by injecting type II collagen for 4 weeks. Next, CIA rats were randomly divided into three groups and injected or transplanted with PBS, IL-1ß siRNA and IL-1ß siRNA + BMSCs for another 4 weeks. The CIA rat model was successfully established, as demonstrated by the higher toe swelling value, thymus and spleen/body weight, immobility time and serum IL-1ß concentration, as well as lower body weight, climbing time and mRNA expression of programmed death-1 (PD-1), transforming growth factor-ß1 (TGF-ß1) and forkhead box protein 3 (Foxp3) in the spleen, compared with control rats. Furthermore, histopathology results demonstrated that joint swelling and redness were observed in the knee joints of CIA rats. H&E results revealed that CIA rats presented erosive destruction of the bone and ulceration of the articular cartilage. In addition, in vitro results demonstrated that IL-1ß expression was successfully silenced after IL-1ß siRNA transfection in lipopolysaccharide-stimulated BMSCs. When compared with the results of PBS rats, both IL-1ß siRNA injection and IL-1ß siRNA + BMSC transplantation significantly increased the body weight, climbing time and mRNA expression of PD-1, TGF-ß1 and Foxp3 in the spleen, while significantly reduced the immobility time and serum IL-1ß concentration. In addition, when compared with that of IL-1ß siRNA injection, IL-1ß siRNA + BMSC transplantation exhibited markedly higher therapeutic efficacy against CIA. These results demonstrated that higher IL-1ß contributed to the pathogenesis of CIA, and that IL-1ß siRNA injection ameliorated CIA, while its combination with BMSCs exerted synergistic effects, which may be beneficial against RA.

4.
Langmuir ; 38(2): 680-688, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34986309

RESUMO

Peptide-based biomaterials exhibit great potentials in developing drug delivery platforms due to their biocompatibility and biodegradability beyond poly(ethylene glycol). How different amino acids in peptides used for delivery play their roles is still unclear at the microscopic level. This work compared the assembly behaviors of a series of peptides around interferon-α (IFN-α). Through all-atom molecular simulations, the sequence effect of peptides on delivering interferon-α was quantitively characterized. The hydrophobic elastin-like peptide (VPGAG)n preferred to self-aggregate into dense clusters, rather than encapsulate IFN-α. The hydrophilic zwitterionic peptides with repeating unit "KE" tended to phase-separate from IFN-α in the mixture. In contrast, peptides with a hybrid sequence, i.e., (VPKEG)n, exhibited the highest contact preference, and the formed protective shell endowed IFN-α with better thermal stability and stealth property and achieved a subtle balance between protecting IFN-α and subsequent releasing. Further energy decomposition analysis revealed that the positively charged Lys contributed most to the binding affinity while the negatively charged Glu contributed most to the hydrophilic property of peptide-based materials. In summary, this article reveals why peptides composed of repeating hydrophobic and charged residues could be a potential choice for delivering therapeutic proteins in the form of solution.

5.
Vet Microbiol ; 265: 109327, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34986434

RESUMO

Pseudorabies is caused by pseudorabies virus (PRV), a member of the Herpesvirus family, and has caused tremendous damage to the pig industry. Protein unique lone 16 (pUL16) is a conserved envelope protein in all herpesviruses, that is known to play an important role in several aspects, including virus diffusion in cells and virulence in mice. It has been shown that the pUL16 can interact with the virus proteins UL11, UL49, UL21, gD, and gE. However, the research to date on pUL16 has only focused on etiology, without discussing the possible cellular pathways involved in PRV infection. Leucine-rich PPR motif-containing protein (LRPPRC) is a multifunctional cellular protein that participates in various cellular processes, such as RNA processing, splicing, stabilization, editing, translation, and energy metabolism. This was the first caspase-independent apoptosis protein to be identified. In this study, immune precipitation and mass spectrometry was performed to define the function of the pUL16 in PRV infection to study the possible cellular pathways in which pUL16 may participate. It was found that LRPRRC could interact with PRV pUL16, which may indicate that UL16 is involved in a redox reaction or cellular apoptosis. This is the first study of the interaction between pUL16 and host proteins, which has positive significance to gain a further understanding of the pUL16.

6.
Cancer Cell Int ; 21(1): 655, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876150

RESUMO

BACKGROUND: SWI/SNF, a well-known ATP-dependent chromatin-remodeling complex, plays an essential role in several biological processes. SNF5, the core subunit of the SWI/SNF remodeling complex, inactivated in 95% of malignant rhabdoid tumors (MRT), highlighting its significance in tumorigenesis. However, the role of SNF5 in bladder cancer (BC) remains unknown. In this study, we aimed to investigate the function and potential clinical applicability of SNF5 in BC. METHODS: Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were used to evaluate the clinical significance of SNF5 in BC. We performed Gene Set Enrichment Analysis (GSEA) and functional assays to investigate the role of SNF5 in BC. Genomics of Drug Sensitivity in Cancer (GDSC) and drug-susceptibility tests were performed to identify the potential value of SNF5 in the treatment of BC. RESULTS: Low SNF5 expression conferred a poor prognosis and was significantly associated with the N-stage in BC. ROC curves indicated that SNF5 could distinguish BC from the normal tissues. In vitro and in vivo functional assays demonstrated that attenuated SNF5 expression could promote cell proliferation and enhance migration by STAT3 activation. We imputed that low SNF5 expression could confer greater resistance against conventional first-line drugs, including cisplatin and gemcitabine in BC. GDSC and drug-resistance assays suggested that low SNF5 expression renders T24 and 5637 cells high sensitivity to EGFR inhibitor gefitinib, and combination of EZH2 inhibitor GSK126 and cisplatin. CONCLUSIONS: To the best of our knowledge, the present study, for the first time, showed that low SNF5 expression could promote cell proliferation and migration by activating STAT3 and confer poor prognosis in BC. Importantly, SNF5 expression may be a promising candidate for identifying BC patients who could benefit from EGFR-targeted chemotherapy or cisplatin in combination with EZH2 inhibitor treatment regimens.

7.
Biochem Cell Biol ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34890285

RESUMO

This study is to reveal the gene transcriptional alteration, possible molecular mechanism, and pathways involved in the synergy of 5-aza-2'-deoxycytidine (DAC) and CDDP in UC. Two UC cell lines, 5637 and T24, were used in the study. A cDNA microarray was carried out to identify critical genes in the synergistic mechanism of both agents against UC cells. The results showed that several key regulatory genes, such as interleukin 24(IL24), fibroblast growth factor 1(FGF1), and transforming growth factor beta-induced (TGFBI), were identified and may play critical roles in the synergy of DAC and CDDP in UC. Pathway enrichment suggested that many carcinogenesis-related pathways, such as ECM-receptor interaction and MAPK signaling pathways, may participate in the synergy of both agents. Our results suggested that TGF-ß1 stimulates the phosphorylation levels of ERK1/2 and p38 via increasing TGFBI expression, TGFBI-MAPK signaling pathway plays an important role in the synergy of DAC and CDDP against UC. Therefore, we revealed the synergistic mechanism of DAC and CDDP in UC, several key regulatory genes play critical roles in the synergy of combined treatment, and TGFBI-MAPK signaling pathway may be an important potential target of these two agents.

8.
J Biol Chem ; 298(1): 101499, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34922943

RESUMO

DNA N6-adenine methylation (6mA), as a novel adenine modification existing in eukaryotes, shows essential functions in embryogenesis and mitochondrial transcriptions. ALKBH1 is a demethylase of 6mA and plays critical roles in osteogenesis, tumorigenesis, and adaptation to stress. However, the integrated biological functions of ALKBH1 still require further exploration. Here, we demonstrate that knockdown of ALKBH1 inhibits adipogenic differentiation in both human mesenchymal stem cells (hMSCs) and 3T3-L1 preadipocytes, while overexpression of ALKBH1 leads to increased adipogenesis. Using a combination of RNA-seq and N6-mA-DNA-IP-seq analyses, we identify hypoxia-inducible factor-1 (HIF-1) signaling as a crucial downstream target of ALKBH1 activity. Depletion of ALKBH1 leads to hypermethylation of both HIF-1α and its downstream target GYS1. Simultaneous overexpression of HIF-1α and GYS1 restores the adipogenic commitment of ALKBH1-deficient cells. Taken together, our data indicate that ALKBH1 is indispensable for adipogenic differentiation, revealing a novel epigenetic mechanism that regulates adipogenesis.

9.
Sensors (Basel) ; 21(24)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34960330

RESUMO

The mega-launch of low Earth orbit satellites (LEOs) represents a critical opportunity to integrate navigation and communication (NavCom), but first, challenges related to signal design must be overcome. This article proposes a novel signal scheme named CE-OFDM-PM. Via research on the in-band or adjacent band, it was found that the proposed signal scheme was suitable for S-band and had a wide normalized power spectrum density (PSD), high peak-to-side lobe ratio (PSR), and multiple peaks in autocorrelation. In an analysis of the simulation performance evaluation in navigation and communication, it is found that the proposed signal scheme has the potential for high accuracy, a code tracking accuracy of up to 0.85 m, a small mutual influence between the proposed signal scheme and other schemes, excellent anti-interference properties, and a better performance at both short and long distances in terms of its anti-multipath capability. Furthermore, the proposed signal scheme shows the ability to communicate between satellites and the ground and is outstanding in terms of its bit error rate (BER), CNR, and energy per bit to noise power spectral density ratio (Eb/N0). From the technical, theoretical, and application perspectives, our proposed signal scheme has potential as an alternative scheme in future BDS, PNTs, and even 5G/B5G.

10.
BMC Nephrol ; 22(1): 410, 2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895156

RESUMO

BACKGROUND: Podocytic infolding glomerulopathy (PIG) is a rare pathological change which was characterized by the microspheres or microtubular structures in the thickened glomerular basement membrane (GBM). Only a few dozen cases have been reported worldwide so far. Here we present a case of PIG with systemic lupus erythematosus. CASE PRESENTATION: A 61-year-old Chinese female was diagnosed with systemic lupus erythematosus with clinical manifestations of proteinuria, pleural effusion, seroperitoneum, anemia, leukopenia, thrombocytopenia, antinuclear antibody positive, and hypocomplementemia. She also had benign ovarian tumor and Epstein-Barr virus infection. Renal biopsy immunofluorescent staining showed IgM and C3 were granularly deposited along the capillary wall instead of typical "full house" features. Electron microscopy showed lots of microspheres structures were seen in the thickened GBM. CONCLUSION: We present a case of PIG in a patient with systemic lupus erythematosus. The mechanisms of PIG are unknown, but may be associated with connective tissue disease and podocyte injury.

11.
Comput Math Methods Med ; 2021: 2380346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745322

RESUMO

Introduction: Radiomics could be potential imaging biomarkers by capturing and analyzing the features. Children and adolescents with CHD have worse neurodevelopmental and functional outcomes compared with their peers. Early diagnosis and intervention are the necessity to improve neurological outcomes in CHD patients. Methods: School-aged TOF patients and their healthy peers were recruited for MRI and neurodevelopmental assessment. LASSO regression was used for dimension reduction. ROC curve graph showed the performance of the model. Results: Six related features were finally selected for modeling. The final model AUC was 0.750. The radiomics features can be potential significant predictors for neurodevelopmental diagnoses. Conclusion: The radiomics on the conventional MRI can help predict the neurodevelopment of school-aged children and provide parents with rehabilitation advice as early as possible.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34723465

RESUMO

The formation of ice hangings on the surfaces of concrete tunnel linings and sloped rock masses in cold regions endangers railroad and highway traffic. However, an inexpensive anti-icing material that meets both performance and cost requirements has not yet been developed for application in tunnel and slope engineering infrastructures in cold regions. Most current advanced anti-icing materials are expensive, and fabrication and spraying are both cumbersome, which limits their widespread application to tunnel and slope engineering. Because concrete is a widely used construction material owing to its excellent mechanical properties and low cost, we developed an inexpensive, environmentally friendly anti-icing concrete material (AICM). The AICM can be easily fabricated and sprayed onto the surfaces of large-area concrete or rock substrates and exhibits excellent superhydrophobicity (CA: 151°, SA: 6.7°), surface robustness, water resistance, chemical durability, good anti-icing, easy deicing (deicing stress: 0.06 MPa), and excellent long-term durability in freeze-thaw cycles in low-temperature environments. In addition, a novel fractal theory-based model of ice adhesion shear stress was developed and revealed the mechanism through which an AICM with a composite micro/nanostructure easily deices. The AICM has good application prospects and serves as an important guide for mitigating the formation of ice hangings in tunnel and slope engineering infrastructures in cold regions.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34725738

RESUMO

PURPOSE: To determine whether TCF-1+PD-1+CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer (NSCLC) patients. METHODS: We investigated the expression of TCF-1+PD-1+CD8+T cells and elucidated their predictive role in NSCLC patients. Pretreatment specimens from 20 advanced NSCLC patients who underwent PD-1 immunotherapy or combined with chemotherapy were analyzed. The frequencies of TCF-1+ cells in PD-1+CD8+T cells were determined in these biospecimens using multi-label immunofluorescence staining and multi-spectral acquisition technology. The clinical roles of TCF-1+PD-1+CD8+T cells were assessed via analyzing our cases and human NSCLC data collected from public databases. RESULTS: A high frequency of TCF-1+PD-1+CD8+T cells was identified in responders compared with non-responders (p = 0.0024), and the patients with high expression of this cell subset had durable clinical benefit of anti-PD-1 therapy. There were no significant association between the expression of TCF-1+PD-1+CD8+T cells and patients' age, smoking history, pathologic type, and genetic status. In univariate analysis by the Cox hazard model, high frequency of TCF-1+ PD-1+ CD8+T cells was significantly correlated with patients' benefit of PD-1 blockade (p = 0.024). CONCLUSION: Our study indicated that TCF-1+PD-1+CD8+T cells are associated with the response to PD-1 blockade, and may be a predictor of anti-PD-1 therapy.

14.
Cell Rep ; 37(5): 109939, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731627

RESUMO

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neurodevelopmental delay. We find that Senp1+/- mice exhibit core autistic-like symptoms such as social deficits and repetitive behaviors but normal learning and memory ability. Moreover, we find that inhibitory and excitatory synaptic functions are severely affected in the retrosplenial agranular (RSA) cortex of Senp1+/- mice. Lack of Senp1 leads to increased SUMOylation and degradation of fragile X mental retardation protein (FMRP), also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescues the defects of synaptic function and autistic-like symptoms of Senp1+/- mice. Together, these results demonstrate that disruption of the SENP1-FMRP regulatory axis in the RSA causes autistic symptoms, providing a candidate region for ASD pathophysiology.

15.
J Clin Invest ; 131(21)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34720095

RESUMO

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Células Matadoras Naturais/imunologia , Receptores de Células Matadoras Naturais/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Animais , Antígenos de Diferenciação de Linfócitos T/imunologia , Moléculas de Adesão Celular/imunologia , Estudos de Coortes , Citotoxicidade Imunológica , Feminino , Xenoenxertos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunofenotipagem , Técnicas In Vitro , Ligantes , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Subfamília D de Receptores Semelhantes a Lectina de Células NK/imunologia , Pandemias , Receptores Imunológicos/imunologia , Receptores Virais/imunologia , Carga Viral , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-34844735

RESUMO

HYPOTHESIS: General strategies leading to 2D assemblies promise a significant step forward in the development of supramolecular materials with diversity and superiority. Considering molecular packing parameter indicates a connection between molecular geometry and aggregate morphology, we predict the introduction of ionic surfactants as assembly crosslinker would be endowed to develop a methodology of 2D supramolecular assembles. EXPERIMENTS: In this work, by introducing ionic surfactants such as sodium dodecylsulfate (SDS), the molecular packing parameter P in bolaamphiphile (A2G) system was increased, which successfully manipulated the transformation of the 3D vesicles into 2D membranes. This 2D membranes further showed excellent light and enzyme response, and thus 2D to 3D morphological conversion can be rationally controlled via UV/Vis light irradiation and alternate addition of ß-CD and α-amylase. Significantly, the 2D feature revealed not only a remarkable fluorescence enhancement to luminescent molecules but also the ability to effectively remove pollutants from water through filtration. FINDINGS: We report a general and facile strategy for the construction of 2D supramolecular membranes, initiated by introducing ionic surfactants as assembly crosslinker to increase P. In the existence of stimulus response factors, 2D↔3D morphological conversion can be further controlled in a flexible manner, which opens up a new paradigm leading to interconvertible supramolecular materials.

17.
Arch Gynecol Obstet ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846571

RESUMO

PURPOSE: This study aimed to investigate the effect of prophylactic uterine artery embolization (UAE) on reproductive outcomes in patients with cesarean scar pregnancy (CSP). METHODS: A retrospective case-control study was conducted using the hospital records of all women diagnosed with CSP during a period of 6 years, between January 2014 and December 2019, at Shengjing Hospital of China Medical University. The clinical characteristics and different treatment modalities were analyzed. According to the inclusion and exclusion criteria, 181 patients with reproductive needs were selected and divided into a UAE group (n = 51) and a non-UAE group (n = 130) according to whether they received preventive UAE before their hysteroscopic or laparoscopic operation. The basic characteristics and pregnancy outcomes of patients in each group were compared, and a propensity score-matched (PSM) analysis was used to produce 37 matched pairs. RESULTS: Before PSM, the UAE group had a thinner muscle layer, larger mass size, and higher serum human chorionic gonadotropin level than the non-UAE group. The pregnancy rate and live birth rate of the UAE group were 54.9% and 61.9%, respectively, which were lower than those of the non-UAE group (61.5% and 66.7%), but no statistical differences were observed. Post-PSM, no significant differences between basic characteristics of the groups were observed. The pregnancy rate of the UAE group was 51.4%, which was lower than that of the non-UAE group (73.0%); the live birth rate of the UAE group was 64.3%, which was also lower than that of the non-UAE group (72.7%); however, the differences were not statistically significant with the P value of 0.077 and 0.716. CONCLUSION: Prophylactic UAE did not induce a significant difference in pregnancy rate and live birth rate between the UAE group and the non-UAE group.

18.
Cell Rep ; 37(6): 109987, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34758320

RESUMO

CENP-A (centromeric protein A), a histone H3 variant, specifies centromere identity and is essential to centromere maintenance. Little is known about how protein levels of CENP-A are controlled in mammalian cells. Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells. We identify two major polyubiquitination sites that are responsible for this phosphorylation-dependent degradation. Substituting the two residues, Lys49 and Lys124, with arginines abrogates proper CENP-A degradation and results in CENP-A mislocalization to non-centromeric regions. Furthermore, we find that DCAF11 (DDB1 and CUL4 associated factor 11/WDR23) is the E3 ligase that specifically mediates the observed polyubiquitination. Deletion of DCAF11 hampers CENP-A degradation and causes its mislocalization. We conclude that the Ser68 phosphorylation plays an important role in regulating cellular CENP-A homeostasis via DCAF11-mediated degradation to prevent ectopic localization of CENP-A during the cell cycle.

19.
Cornea ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34759200

RESUMO

PURPOSE: The purpose of this study was to assess the distribution and morphological variation of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects and patients with meibomian gland dysfunction (MGD) using laserscanningin vivo confocal microscopy. METHODS: A total of 34 healthy subjects and 32 patients with MGD were enrolled. All subjects underwent a conventional examination consisting of slitlamp biomicroscopy, tear film break-up time, and the Schirmer test. In vivo microscopy was applied to analyze the morphological changes in the diffuse lymphoid layer and lymphoid follicles in CALT. Conjunctival impression cytology (CIC) of samples of patients' palpebral conjunctiva and immunofluorescence staining of CD4 and CD8 antibodies were also performed to indicate the immune response status of CALT. RESULTS: In the MGD group, the density of diffuse lymphocytes (P < 0.001), follicles (P < 0.001), and perifollicular lymphocytes was higher (P < 0.001) and the central reflection of the follicles was stronger (P < 0.001) than in the control group, while there was no difference in the follicle area (P = 0.758). Besides, diffuse lymphocyte density was correlated with telangiectasia, and follicular center reflection intensity was correlated with plugging. CIC immunofluorescence staining showed a higher percentage of CD4+ (P < 0.001) and CD8+ (P < 0.001) cells in the MGD group than in the control group. CONCLUSIONS: Using laser scanning in vivo confocal microscopy and CIC immunofluorescence staining, we observed the activation of CALT in patients with MGD, and some CALT-related parameters correlated with the lid margin findings of patients with MGD.

20.
Transl Pediatr ; 10(9): 2313-2324, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733672

RESUMO

Background: The gut microbiome plays a potential role in clinical events in preterm infants and may affect their lateral development. Understanding the initial colonization of microbes in the gut, their early dynamic changes, and the major factors correlated with these changes would provide crucial information about the developmental process in early life. Methods: The present study enrolled 151 preterm infants and examined the longitudinal dynamics of their fecal microbiome profiles during the period of hospitalization using 16S ribosomal RNA gene sequencing. Random forest modeling was used to predict postnatal age (Age), postmenstrual age (PMA), and gestational age (GA), using gut microbiome features. Results: Principal coordinate analysis revealed that the gut microbiome of the preterm infants displayed an obvious time-dependent change pattern, which showed the strongest association with Age, followed by PMA, and a much weaker association with (GA). Random forest modeling further evidenced the time-dependent change pattern, with the Pearson's correlation coefficients between the actual values and the gut microbiome-predicted values being 0.68, 0.53, and 0.38 for postnatal, postmenstrual, and gestational age, respectively. The microbiome dynamism could be further divided into four Age stages, each with its own characteristic microbial taxa. The first 1-4 days (T1 stage) represented the meconium microbiome, with colonization of a high diversity of microbes before or during delivery. During 5-15 days (T2 stage), the gut microbiome of the preterm infants underwent a rapid turnover, in which microbial diversity declined, and stabilized afterward. Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Staphylococcaceae, and Clostridiaceae were the major classes in the gut microbiome in the lateral stages of development (T3-T4 stage). Conclusions: Postnatal age, rather than the gestational age, is significantly correlated with the gut microbiome of preterm infants, suggesting that clinical interventions contribute more to the early dynamics of gut microbiome in preterm infants than the natural development of the gut.

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