Optical pulse modulators based on layered vanadium diselenide nanosheets.

The transition metal disulfides of VB group elements have gradually come into people's field of vision owing to their two-dimensional structure and unique optical properties. Vanadium diselenide (VSe2) as a kind of transition metal diselenides, is competent for the applications of nonlinear saturable absorption. The dispersion of few-layer VSe2is prepared by liquid phase exfoliation method. Clearly, it has an obvious layered structure, and the interlayer spacing is 0.31 nm. The VSe2nanosheets are inserted into the Erbium-doped fiber laser through tapered deposition method and the measured modulation depth is 1.46%. A 1530.5 nm centered 851-fs pulse is observed with the 3.2 nm 3-dB spectral width. The experimental results show that the pulse is persistent under the power of 334 mW, with signal-to-noise ratio of 41 dB. And an up to 552.4 MHz modulation phenomenon is observed around 1560 nm, so is its frequency tunability. This is the first time that VSe2is used to realize high frequency modulation in fiber laser. It is proved that VSe2is expected to be a budding material of ultrafast optical modulation devices and widely used in the field of ultrafast photonics.

Metabolic network-based identification of plasma markers for non-small cell lung cancer.

Metabolic markers, offering sensitive information on biological dysfunction, play important roles in diagnosing and treating cancers. However, the discovery of effective markers is limited by the lack of well-established metabolite selection approaches. Here, we propose a network-based strategy to uncover the metabolic markers with potential clinical availability for non-small cell lung cancer (NSCLC). First, an integrated mass spectrometry-based untargeted metabolomics was used to profile the plasma samples from 43 NSCLC patients and 43 healthy controls. We found that a series of 39 metabolites were altered significantly. Relying on the human metabolic network assembled from Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we mapped these differential metabolites to the network and constructed an NSCLC-related disease module containing 23 putative metabolic markers. By measuring the PageRank centrality of molecules in this module, we computationally evaluated the network-based importance of the 23 metabolites and demonstrated that the metabolism pathways of aromatic amino acids and long-chain fatty acids provided potential molecular targets of NSCLC (i.e., IL4l1 and ACOT2). Combining network-based ranking and support-vector machine modeling, we further found a panel of eight metabolites (i.e., pyruvate, tryptophan, and palmitic acid) that showed a high capability to differentiate patients from controls (accuracy > 97.7%). In summary, we present a meaningful network method for metabolic marker discovery and have identified eight strong candidate metabolites for NSCLC diagnosis.

MiR-200a and miR-200b restrain inflammation by targeting ORMDL3 to regulate the ERK/MMP-9 pathway in asthma.

BACKGROUND: Asthma is one of the most frequent and serious diseases worldwide. Inflammation has been reported to correlate with airway remodeling, which is critical for the progression of asthma. Better understanding of novel molecules modulating asthma and the underlying mechanism will benefit explorations of new treatments. Method: To explore the role of miR-200a and miR-200b in asthma, miR-200a mimics/inhibitor and miR-200b mimics/inhibitor were employed in A549 cells, respectively. Expression levels of inflammatory cytokines, including TNF-α, IL-4, IL-5, IL-13 and IL-1ß, were measured by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). A dual luciferase reporter assay was performed to identify whether miR-200a/200b directly bound to Orosomucoid 1-like 3 (ORMDL3). ERK, p-ERK and MMP-9, involved in downstream pathways of ORMDL3, were detected using qRT-PCR and western blotting. Results: MiR-200a/200b silencing significantly increased the expression of inflammatory cytokines, including TNF-α, IL-4, IL-5, IL-13 and IL-1ß, in A549 cells. ORMDL3 was the target gene of miR-200a/200b, with high expression levels in miR-200a inhibitor and miR-200b inhibitor groups. MiR-200a and miR-200b played synergistic roles in the regulation of the inflammatory effect in A549 cells. Expression levels of p-ERK and MMP-9 were significantly increased in miR-200a inhibitor and miR-200b inhibitor groups and were rescued by ERK inhibitor and MMP-9 inhibitor, respectively. Conclusion: These findings suggest that miR-200a and miR-200b are required to regulate asthma inflammation. Reduction in miR-200a/200b promotes the development of asthma inflammation by targeting ORMDL3 to activate the ERK/MMP-9 pathway. Therefore, elevating miR-200a and miR-200b and decreasing ORMDL3 might be potential strategies for inhibition of the asthma process.

Higher expression levels of aquaporin (AQP)1 and AQP5 in the lungs of arid-desert living Lepus yarkandensis.

Water transport across epithelial cells that line the airways and alveoli is a crucial component of lung physiology. Aquaporins (AQPs) facilitate water transport across the air space-capillary barrier in the distal lung. However, the roles of lung AQPs in desert animal adaptation to dry airstream environments are still unclear. A hare (Lepus yarkandensis) only lives in the Tarim Basin, and its living environment is an arid climate with rare precipitation. We studied cellular localization and expression levels of AQP1, AQP3, AQP4 and AQP5 in L. yarkandensis lungs by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot. The lung of rabbits (Oryctolagus cuniculus) that inhabit in mesic environment was similarly studied. Obtained results in two species of animals were compared to investigate whether AQPs in the lung altered expression in the animal living in arid region. AQP1 was localized to the endothelial cells in capillaries and venules surrounding terminal bronchioles and alveoli. AQP5 was localized to the ciliated columnar cells in terminal bronchioles and the alveolar type I cells in the alveolus. Quantitative real-time PCR analysis showed higher AQP1 and AQP5 mRNA levels in L. yarkandensis compared to O. cuniculus. Similar results were obtained by Western blot. These results revealed that the higher expression levels of AQP1 and AQP5 played a significant role in water transport in the lungs of arid-desert living L. yarkandensis and might accelerate water transport from capillary compartments to the airspace.

Quantitative characterization of glutaminolysis in human plasma using liquid chromatography-tandem mass spectrometry.

Glutaminolysis is the metabolic pathway that lyses glutamine to glutamate, alanine, citrate, aspartate, and so on. As partially recruiting reaction steps from the tricarboxylic acid (TCA) cycle and the malate-aspartate shuttle, glutaminolysis takes essential place in physiological and pathological situations. We herein developed a sensitive, rapid, and reproducible liquid chromatography-tandem mass spectrometry method to determine the perturbation of glutaminolysis in human plasma by quantifying 13 involved metabolites in a single 20-min run. A pHILIC column with a gradient elution system consisting of acetonitrile-5 mM ammonium acetate was used for separation, while an electrospray ionization source (ESI) operated in negative mode with multiple reaction monitoring was employed for detection. The method was fully validated according to FDA's guidelines, and it generally provided good results in terms of linearity (the correlation coefficient no less than 0.9911 within the range of 0.05-800 µg/mL), intra- and inter-day precision (less than 18.38%) and accuracy (relative standard deviation between 89.24 and 113.4%), with lower limits of quantification between 0.05 and 10 µg/mL. The new analytical approach was successfully applied to analyze the plasma samples from 38 healthy volunteers and 34 patients with type 2 diabetes (T2D). Based on the great sensitivity and comprehensive capacity, the targeted analysis revealed the imperceptible abnormalities in the concentrations of key intermediates, such as iso-citrate and cis-aconitate, thus allowing us to obtain a thorough understanding of glutaminolysis disorder during T2D. Graphical abstract ᅟ.

Human Umbilical Cord Mesenchymal Stem Cell Exosome-derived miR-335-5p Alleviated Lipopolysaccharide-induced Acute Lung Injury by Regulating the m6A Level of ITGß4 Gene.

BACKGROUND: Acute lung injury (ALI) is a serious complication that may accompany severe pneumonia in children. Derived from exosomes of human umbilical cord mesenchymal stem cell exosome (HucMSC-Exo) can contribute to the regeneration of damaged lung tissue. This study aims to investigate the impact of HucMSC-Exo on ALI and its potential mechanisms. METHODS: Firstly, RT-qPCR was performed to assess the expression of miR-335-5p. Subsequently, Pearson correlation analysis was performed to examine the correlation between METTL14 and miR-335-5p, as well as the correlation between METTL14 and ITGB4., while RNA immunoprecipitation (RIP) was used to determine the m6A modification level of ITGß4. Additionally, molecular biology techniques were employed to evaluate the expression of glycolysis-related factors. Definitively, an LPS-induced ALI model was established to investigate the effect of miR-335-5p on mice lung tissue. RESULTS: miR-335-5p was found to be highly expressed in HucMSC-Exo. Transfection with miR-335-5p mimics resulted in increased glucose uptake. Pearson correlation analysis revealed a negative correlation between METTL14 and miR-335-5p, as well as between METTL14 and ITGß4. The m6A level of ITGß4 was elevated in ALI. Overexpression of METTL14 was found to reduce the expression and glucose uptake of ITGß4, while overexpression of ITGß4 reversed the effects of METTL14 overexpression. in vivo, results demonstrated that miR-335-5p can improve the extent of lung tissue lesions and reduce glycolytic levels. CONCLUSION: This study reveals the mechanism by which miR-335-5p derived from HucMSC-Exo could alleviate LPS-induced ALI by regulating the m6A modification of ITGß4, providing a new direction for the treatment of ALI.

The causal relationship between autoimmune diseases and age-related macular degeneration: A two-sample mendelian randomization study.

OBJECTIVE: The aim of this study is to investigate the potential causal relationship between autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and age-related macular degeneration (AMD). By utilizing the two-sample Mendelian Randomization (MR) approach, we endeavor to address this complex medical issue. METHODS: Genome-wide association study (GWAS) data for autoimmune diseases and AMD were obtained from the IEU Open GWAS database and the FinnGen consortium. A series of stringent SNP filtering steps was applied to ensure the reliability of the genetic instruments. MR analyses were conducted using the TwoSampleMR and MR-PRESSO packages in R. The inverse-variance weighted (IVW) method served as the primary analysis, complemented by multiple supplementary analyses and sensitivity tests. RESULTS: Within the discovery sample, only a statistically significant inverse causal relationship between multiple sclerosis (MS) and AMD was observed (OR = 0.92, 95% CI: 0.88-0.97, P = 0.003). This finding was confirmed in the replication sample (OR = 0.85, 95% CI: 0.80-0.89, P = 3.32×10-12). No statistically significant associations were detected between systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Type 1 diabetes and AMD. CONCLUSION: Strong evidence is provided by this study to support the existence of an inverse causal relationship between multiple sclerosis and age-related macular degeneration. However, no causal evidence was found linking other autoimmune diseases with AMD. These findings not only offer novel insights into the potential etiological mechanisms underlying AMD but also suggest possible directions for future clinical interventions.

lncRNA NEAT1 promotes hypoxia-induced inflammation and fibrosis of alveolar epithelial cells via targeting miR-29a/NFATc3 axis.

The objective of the present study was to explore the function and mechanism of long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in pulmonary fibrosis (PF) progression. HPAEpic cells and A549 cells were exposed to hypoxic conditions to establish an in vitro model. Cell apoptosis was detected by TUNEL assay, and inflammatory cytokine levels were detected by ELISA. Gene and protein expression levels were identified by qRT-PCR and Western blot assays, respectively. The interaction among NEAT1, miR-29a, and NFATc3 was identified by dual-luciferase reporter and RNA pull-down assays. In hypoxia-treated cells, hypoxia markers (HIF-1α and HIF-2α), cytokines (TNF-α, IL-1ß, and IL-6) and fibrotic markers (α-SMA, collagen I and collagen III) were significantly enhanced. Consistently, the expression levels of NEAT1 and NFATc3 were increased, but miR-29a was decreased in hypoxia-stimulated cells. Knockdown of NEAT1 significantly decreased cell apoptosis and the releases of TNF-α, IL-1ß, and IL-6 as well as reduced the levels of α-SMA, collagen I, and collagen III. Moreover, NEAT1 positively regulated NFATc3 expression by directly targeting miR-29a. Functional experiments showed that the anti-apoptotic, anti-inflammatory, and anti-fibrotic effects mediated by NETA1 silencing were impeded by miR-29a inhibition or NFATc3 overexpression in hypoxia-stimulated HPAEpic and A549 cells. Collectively, these data demonstrated that NEAT1 knockdown inhibited hypoxia-induced cell apoptosis, inflammation, and fibrosis by targeting the miR-29a/NFATc3 axis in PF, suggesting that NEAT1 might be a potential therapeutic target for relieving PF progression.

NRG1 regulates Fra-1 transcription and metastasis of triple-negative breast cancer cells via the c-Myc ubiquitination as manipulated by ERK1/2-mediated Fbxw7 phosphorylation.

Neuregulin 1 (NRG1), an EGF family member, is expressed in most breast cancers. It promotes breast cancer growth and metastasis in HER2 receptor expressing breast cancer. However, its role in triple-negative breast cancer (TNBC) has not been extensively investigated. In this study, we observed that NRG1 knockdown resulted in the suppression of TNBC cells (MDA-MB-231 cell and MDA-MB-468 cell) metastasis and downregulation of Fra-1 (FOS-like 1, AP-1 transcription factor subunit, which is an overexpressed transcription factor in TNBC and acts as a coordinator of metastasis). In addition, the transcriptional regulation of Fra-1 by NRG1 was mediated by ERK1/2-induced recruitment of c-Myc (MYC proto-oncogene, transcription factor) to the promoter of Fra-1. Furthermore, c-Myc was targeted by an E3 ligase Fbxw7 and its ubiquitination and degradation by Fbxw7 was regulated by NRG1 expression and ERK1/2-mediated Fbxw7 phosphorylation that results in the dissociation and nuclear import of c-Myc. Taken together, the results of our study demonstrated that NRG1 regulates the Fra-1 expression to coordinate the TNBC metastasis via the novel ERK1/2-Fbxw7-c-Myc pathway and targeting NRG1 expression could be a potential therapeutic strategy for TNBC.

AMG487 inhibits PRRSV replication and ameliorates lung injury in pig lung xenografts by down-regulating the expression of ANXA2.

Porcine reproductive and respiratory syndrome (PRRS) is a pig disease caused by the PRRS virus (PRRSV) that is characterized with diffuse interstitial pneumonia and lung edema. High expressions of chemokine CXCL10 and its receptor CXCR3 are reported in infected porcine lungs. Since CXCR3 is a key player in host inflammatory response, it might be a therapeutic target to treat lung damage caused by PRRSV infection. The size of pigs has long hampered research into molecular mechanisms of PRRS and validating the potential pharmaceutical targets. In this study, a porcine lung xenograft model with PRRSV infection was generated in immunodeficient mice to evaluate the therapeutic effects of the CXCR3 antagonist AMG487 on PRRSV infection-induced lung injury. The porcine lung tissues developed normally two weeks after xeno-transplantation in the mouse kidney capsule. Infection of PRRSV resulted in its efficient replication in the xenografts and histological damage to the porcine lung tissue structure, with no or little effects on mouse lungs. AMG487 administration dramatically reduced the number of PRRSV genome copies and significantly alleviated the porcine lung injury. Furthermore, treatment of AMG487 in cultured porcine macrophages consistently suppressed PRRSV replication with significant downregulation of Annexin A2 (ANXA2), a cellular protein facilitating viral replication. These findings provide a suitable model for evaluating new antiviral therapies as well as a possible therapeutic option for virus infection-induced lung injury.

The relationship between ApoE gene polymorphism and the efficacy of statins controlling hyperlipidemia.

OBJECTIVE: To explore the relationship between ApoE gene polymorphism and clinical efficacy of statins on lipidemia. METHODS: Peripheral venous blood was obtained from 220 patients with hyperlipidemia who were admitted to the outpatient department of our hospital. The potential relationship between ApoE gene polymorphism and clinical effect of statins was analyzed. RESULTS: In the three isomers (E2, E3, E4) of ApoE, expression level of ApoE protein in ApoE4 gene carriers was significantly different from that in E2 or E3 gene carriers (both P<0.05). At the same time, both the decrease rate of total cholesterol (TC) in blood lipid and low density lipoprotein cholesterol (LDL-C) and the rise rate of high density lipoprotein cholesterol (HDL-C) in ApoE4 carriers after taking statins were much lower than those in non-ApoE4 patients (P<0.05). CONCLUSION: ApoE gene polymorphism is associated with hyperlipidemia and has certain influence on the clinical efficacy of statins in treatment of hyperlipidemia.

MNK as a potential pharmacological target for suppressing LPS-induced acute lung injury in mice.

Acute lung injury (ALI) or its more severe form, known as acute respiratory distress syndrome (ARDS), is characterized by an initial exudative phase, expression of proinflammatory mediators, activation of inflammatory leukocytes, and impairment of the lung endothelium and epithelium. Despite numerous, novel therapeutic strategies have been developed regarding the pathophysiology of ALI, current treatment is mainly supportive, as specific therapies have not been established in the past few decades. The MAP kinase-interacting kinases (MNK1 and MNK2) are serine threonine kinases which are activated by mitogen-activated protein kinases (MAPKs), regulate protein synthesis by phosphroylating eukaryotic translation initiation factor 4E (eIF4E). Although studies have shown that MAPKs pathway is involved in anti-inflammatory and preventing tissue injury processes, the role of MNKs in ALI has, until now, remained relatively unexplored. Here, we investigated whether partial inhibition of MAPKs pathway by targeting MNKs was effective in the prevention and treatment of ALI. C57BL6 mice were pretreated with MNK1 and MNK2 inhibitor (CGP57380, 30 mg/kg) for 30 min and then challenged with 5 mg/kg LPS for 6 h. The results showed that pretreatment with CGP57380 not only significantly attenuated LPS-induced lung wet/dry ratio, as well as protein content, total cells and neutrophils in bronchoalveolar lavage fluid (BALF), but also decreased the production of pro-inflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and keratinocyte-derived chemoattractant (KC). In addition, CGP57380 was observed to significantly suppress LPS-stimulated phosphorylation of eIF4E and MAPKs in the mouse bone marrow-derived macrophages (BMDMs). The involvement of MNK2 in lung injury was further evident by MNK2 knockout mice. MNK2 deficiency resulted in the attenuated lung histopathological changes, as also reflected by reductions in neutrophil counts, and the less LPS-induced the production of IL-6, TNF-α and KC in mouse BALF. Taken together, these findings demonstrated for the first time that MNK inhibition could effectively reduce the LPS-induced ALI in mice, suggesting a novel and potential application for MNK-based therapy to treat this serious disease.

Comparisons of retinal vessel density and glaucomatous parameters in optical coherence tomography angiography.

PURPOSE: To compare the retinal vessel density and glaucomatous parameters in primary angle closure glaucoma (PACG), to evaluate the diagnostic and monitoring abilities of the peripapillary and macular vessel density in the progression of glaucoma. METHODS: This was a observational, prospective and cross-sectional study. According to Glaucoma Staging System, 218 eyes (116 participants) were divided into 5 groups: no glaucoma, early glaucoma, moderate glaucoma, advance glaucoma, severe glaucoma. All participants underwent a comprehensive ocular examination, which included corrected distance visual acuity measurement, slit-lamp biomicroscopy, intra ocular pressure (IOP), gonioscopy, fundus examination, stereoscopic optic disc photography, Humphrey visual field test(VF), peripapillary and macular optical coherence tomography angiography(OCTA) scan. SPSS software was used to calculate and compare retinal vessel density (peripapillary vessel density, PVD and macular vessel density, MVD) and glaucomatous parameters (mean deviation (MD),pattern standard deviation(PSD), retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer(GCIPL),rim area, average cup/disc(C/D) ratio). RESULTS: The GCIPL thickness, RNFL thickness, PVD and MVD are significantly reduced in PACG. There were significant differences in all measurements among the groups (P<0.01).Reduced peripapillary and macular vessel density in glaucoma were detected and a statistically significant correlation with glaucoma stages (P<0.01). In addition, the results of retinal vessel density, reduced RNFL thickness and GCIPL thickness were also statistically related to the stage of glaucoma. As expected, the rim area was significantly smaller with higher C/D area ratios in glaucomatous eyes corresponding to the severity of disease. CONCLUSIONS: The changes of PVD and MVD had strongly positive correlation with GCIPL thickness and RNFL thickness, had negative correlation with the severity of glaucoma, which meant the more severe the glaucoma was, the lower PVD and MVD were. Compared to traditional glaucoma staging system judged by VF, the changes of PVD and MVD obtained by OCTA might be a new method to grade the stage of glaucoma. These findings theorize that the changes of PVD and MVD may be better facilitated for the observation and monitoring of glaucoma progression.

The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29.

Endogenous miR22 is associated with a diverse range of biological processes through post-translational modification of gene expression and its deregulation results in various diseases including cancer. Its expression is usually tissue or cell-specific, however, the reasons behind this tissue or cell specificity are not clearly outlined till-date. Therefore, our keen interest was to investigate the mechanisms of tissue or cell-specific expression of miR22. In the current study, miR22 expression showed a tissues-specific difference in the poly(I:C) induced inflammatory mouse lung and brain tissues. The cell-specific different expression of miR22 was also observed in inflammatory glial cells and endothelial cells. The pattern of RPL29 expression was also similar to miR22 in these tissues and cells under the same treatment. Interestingly, the knockdown of RPL29 exerted an inhibitory effect on miR22 and its known transcription factors including Fos-B and c-Fos. Fos-B and c-Fos were also differentially expressed in the two cell lines transfected with poly(I:C). The knockdown of c-Fos also exerted its negative effects on miR22 expression in both cells. These findings suggest that RPL29 might have regulatory roles on tissue or cell-specific expression of miR22 through the transcription activities of c-Fos and also possibly through Fos-B.

Dynamical behaviour of a Lotka-Volterra competitive-competitive-cooperative model with feedback controls and time delays.

The aim of this paper is to investigate the dynamical behaviour of a class of three species Lotka-Volterra competitive-competitive-cooperative models with feedback controls and time delays. By developing a new analysis technique, we obtain some sufficient conditions that ensure these models have the dynamical property of permanence. We also give some sufficient conditions that guarantee the global attractivity of positive solutions for this system by constructing a new suitable Lyapunov function. Finally, we give some numerical simulations to illustrate our results in this paper.

Elevated plasma soluble (pro)renin receptor levels are associated with left ventricular remodeling and renal function in chronic heart failure patients with reduced ejection fraction.

Soluble (pro)renin receptor [s(P)RR], which is generated from cleavage of (P)RR, can be detected in plasma and urine. s(P)RR levels can reflect the severity of some diseases, such as renal lesions, gestational diabetes mellitus or hypertension, and obstructive sleep apnea syndrome. However, the relationship between s(P)RR levels and the severity of chronic heart failure remains undetermined. We studied s(P)RR levels in 118 patients with chronic heart failure with reduced ejection fraction (HFrEF), including 86 without renal dysfunction (HF) and 32 with renal dysfunction (HF + RF), and 28 healthy subjects (HS) to reveal the relationship between s(P)RR levels and other HFrEF parameters. Plasma s(P)RR levels were 22.2 ±â€¯4.1 ng/mL (HS), 26.4 ±â€¯5.3 ng/ mL (HF) and 30.0 ±â€¯5.3 ng/mL (HF + RF). Plasma s(P)RR levels were significantly higher in the HF group than in the HS group (P < 0.001) and even more increased in the HF + RF group (P < 0.001 vs. the HS group and P < 0.05 vs. the HF group). Multivariate regression analysis revealed that the left ventricular mass index (LVMI) and estimated glomerular filtration rate (eGFR) were independently related to s(P)RR levels in HFrEF patients. In conclusion, high plasma s(P)RR levels are associated with left ventricular remodeling and, especially, with renal dysfunction. Therefore, s(P)RR is a promising evaluative indicator for the severity of HFrEF patients.

Synthesis of mulberry leaf extract mediated gold nanoparticles and their ameliorative effect on Aluminium intoxicated and diabetic retinopathy in rats during perinatal life.

The present report showed the green synthesis of Silver nanoparticles (AgNPs) using Mulberry leaf extract via an environment friendly approach and investigated to know the probable ameliorative effect via biochemical assessment on retinopathy of rats that are maternally subjected to Al intoxication and diabetes. Mulberry leaf extract biomolecules act as capping and reducing agent for fabrication of AgNPs. Later, the fabricated AgNPs were characterized by using spectroscopic and microscopic instrumental techniques such as HR-TEM, UV-Vis, XRD and FT-IR. EDS, XRD and TEM have confirmed the synthesis of AgNPs. HRTEM results exhibited that the formed AgNPs are polydispersed and spherical in nature with mean particle size of 35 nm. Microscopic observation of retina in Al-intoxicated and diabetic mother rats showed abnormal changes in retinal cell layers. Yet, the retina of rats that are maternally received AgNPs plus diabetes or Al-intoxicated exhibited noticeable amelioration. However, lower ameliorations were found in rat's retina that are maternally undergone for combined exposure. Additionally, biochemical assessment revealed that the application of AgNPs caused the amelioration of the changes in Al concentration and maternal serum glucose. The present study revealed that AgNPs are active against diabetic and Aluminium-persuaded developmental retinopathy.

Angiogenesis-related genes may be a more important factor than matrix metalloproteinases in bronchopulmonary dysplasia development.

We characterized the expression profile of angiogenesis-related genes (ARG) and matrix metalloproteinase (MMP) genes in preterm infants, with and without bronchopulmonary dysplasia (BPD). We reanalyzed a gene expression dataset for preterm infants from the Gene Expression Omnibus database using the Gene-Cloud of Biotechnology Information platform. A total of 1,652 genes were differentially (1.2-fold change) expressed: 811 were highly expressed in infants with BPD, and 841 were highly expressed in those without BPD. Twenty-eight and 11 ARGs were upregulated in infants with and without BPD, respectively. Among 27 detected MMPs and TIMPs, MMP8, MMP9, MMP25, TIMP2 and TIMP3 were differently expressed. Levels of THBS1, MMP8, MMP9, MMP25, TIMP2 and TIMP3 increased as severity of BPD and retinopathy of prematurity (ROP) increased, whereas ETS1, LEF1 and SPOCK2 exhibited the opposite trend. Expression of ETS1 and LEF1 had a fitting rate of R2 = 0.849 and P < 0.001. ELISAs showed a positive correlation between THBS1 and CD36 (receptor of THBS1) levels in serum samples from preterm infants. Our study indicates that the upregulation of THBS1 and downregulation of ETS1, LEF1 promotes BPD in preterm infants by disrupting blood vessel formation rather than by dysregulation of MMPs and TIMPs.

The prognostic value of tumor budding in invasive breast cancer.

We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.