Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3.

BACKGROUND: Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). Neuronal/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release. METHODS: A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT/A in inhibiting CNV via SOCS3. FINDINGS: In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased > 30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3. CONCLUSION: BoNT/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal/glial cells. BoNT/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT/A as a therapeutic intervention for pathological angiogenesis in retinopathies.

Photoreceptors inhibit pathological retinal angiogenesis through transcriptional regulation of Adam17 via c-Fos.

Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.

SOCS3 regulates pathological retinal angiogenesis through modulating SPP1 expression in microglia and macrophages.

Pathological ocular angiogenesis has long been associated with myeloid cell activation. However, the precise cellular and molecular mechanisms governing the intricate crosstalk between the immune system and vascular changes during ocular neovascularization formation remain elusive. In this study, we demonstrated that the absence of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells led to a substantial accumulation of microglia and macrophage subsets during the neovascularization process. Our single-cell RNA sequencing data analysis revealed a remarkable increase in the expression of the secreted phosphoprotein 1 (Spp1) gene within these microglia and macrophages, identifying subsets of Spp1-expressing microglia and macrophages during neovascularization formation in angiogenesis mouse models. Notably, the number of Spp1-expressing microglia and macrophages exhibited further elevation during neovascularization in mice lacking myeloid SOCS3. Moreover, our investigation unveiled the Spp1 gene as a direct transcriptional target gene of signal transducer and activator of transcription 3. Importantly, pharmaceutical activation of SOCS3 or blocking of SPP1 resulted in a significant reduction in pathological neovascularization. In conclusion, our study highlights the pivotal role of the SOCS3/STAT3/SPP1 axis in the regulation of pathological retinal angiogenesis.

FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis-Brief Report.

BACKGROUND: BETs (bromodomain and extraterminal domain-containing epigenetic reader proteins), including BRD4 (bromodomain-containing protein 4), orchestrate transcriptional programs induced by pathogenic stimuli, as intensively studied in cardiovascular disease and elsewhere. In endothelial cells (ECs), BRD4 directs induced proinflammatory, proatherosclerotic transcriptional responses; BET inhibitors, like JQ1, repress these effects and decrease atherosclerosis. While BET effects in pathogenic conditions have prompted therapeutic BET inhibitor development, BET action under basal conditions, including ECs, has remained understudied. To understand BET action in basal endothelial transcriptional programs, we first analyzed EC RNA-Seq data in the absence versus presence of JQ1 before using BET regulation to identify novel determinants of EC biology and function. METHODS: RNA-Seq datasets of human umbilical vein ECs without and with JQ1 treatment were analyzed. After identifying C12orf34, also known as FAM222A (family with sequence similarity 222 member A), as a previously unreported, basally expressed, potently JQ1-induced EC gene, FAM222A was studied in endothelial and angiogenic responses in vitro using small-interference RNA silencing and lentiviral overexpression, in vitro, ex vivo and in vivo, including aortic sprouting, matrigel plug assays, and murine neonatal oxygen-induced retinopathy. RESULTS: Resting EC RNA-Seq data indicate BETs direct transcriptional programs underlying core endothelial properties including migration, proliferation, and angiogenesis. BET inhibition in resting ECs also significantly induced a subset of mRNAs, including FAM222A-a unique BRD4-regulated gene with no reported EC role. Silencing endothelial FAM222A significantly decreased cellular proliferation, migration, network formation, aorta sprouting, and Matrigel plug vascularization through coordinated modulation of VEGF (vascular endothelial growth factor) and NOTCH mediator expression in vitro, ex vivo, in vivo; lentiviral FAM222A overexpression had opposite effects. In vivo, siFAM222A significantly repressed retinal revascularization in neonatal murine oxygen-induced retinopathy through similar angiogenic signaling modulation. CONCLUSIONS: BET control over the basal endothelial transcriptome includes FAM222A, a novel, BRD4-regulated, key determinant of endothelial biology and angiogenesis.

1200-W all polarization-maintaining fiber GHz-femtosecond-pulse laser with good beam quality.

In this work, we demonstrate a 1200-W average power all polarization-maintaining (PM) fiber ultrafast laser system operating at 1.0 µm. In accordance with the numerical modeling, the PM fiber laser system is designed and it delivers linearly-polarized femtosecond pulses at a 1.39-GHz fundamental repetition rate, with a maximum output power of 1214 W - to the best of our knowledge, the highest average power from all PM fiber ultrafast laser at 1.0 µm to date. The pulse width can be compressed to ∼800 fs with a beam quality of M2 < 1.1. This kilowatt-class all PM fiber laser system is expected to open new potential for high energy pulse generation through temporal coherent combination and laser ablation using GHz burst fs laser.

Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.

The eye is an immune privileged tissue that insulates the visual system from local and systemic immune provocation to preserve homeostatic functions of highly specialized retinal neural cells. If immune privilege is breached, immune stimuli will invade the eye and subsequently trigger acute inflammatory responses. Local resident microglia become active and release numerous immunological factors to protect the integrity of retinal neural cells. Although acute inflammatory responses are necessary to control and eradicate insults to the eye, chronic inflammation can cause retinal tissue damage and cell dysfunction, leading to ocular disease and vision loss. In this review, we summarized features of immune privilege in the retina and the key inflammatory responses, factors, and intracellular pathways activated when retinal immune privilege fails, as well as a highlight of the recent clinical and research advances in ocular immunity and ocular vascular diseases including retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy.

MARF: Multiscale Adaptive-Switch Random Forest for Leg Detection With 2-D Laser Scanners.

For the 2-D laser-based tasks, e.g., people detection and people tracking, leg detection is usually the first step. Thus, it carries great weight in determining the performance of people detection and people tracking. However, many leg detectors ignore the inevitable noise and the multiscale characteristics of the laser scan, which makes them sensitive to the unreliable features of point cloud and further degrades the performance of the leg detector. In this article, we propose a multiscale adaptive-switch random forest (MARF) to overcome these two challenges. First, the adaptive-switch decision tree is designed to use noise-sensitive features to conduct weighted classification and noise-invariant features to conduct binary classification, which makes our detector perform more robust to noise. Second, considering the multiscale property that the sparsity of the 2-D point cloud is proportional to the length of laser beams, we design a multiscale random forest structure to detect legs at different distances. Moreover, the proposed approach allows us to discover a sparser human leg from point clouds than others. Consequently, our method shows an improved performance compared to other state-of-the-art leg detectors on the challenging Moving Legs dataset and retains the entire pipeline at a speed of 60+ FPS on low-computational laptops. Moreover, we further apply the proposed MARF to the people detection and tracking system, achieving a considerable gain in all metrics.

The complete chloroplast genome sequences of three lilies: genome structure, comparative genomic and phylogenetic analyses.

We sequenced and analyzed the complete chloroplast genomes of Lilium amoenum, Lilium souliei, and Nomocharis forrestii in detail, including the first sequence and structural comparison of Nomocharis forrestii. We found that the lengths and nucleotide composition of the three chloroplast genes showed little variation. The chloroplast genomes of the three Lilium species contain 87 protein coding genes (PCGs), 38 tRNAs, and 8 rRNA genes. The only difference is that Nomocharis forrestii had an additional infA pseudogene. In the sequence analysis of the Lilium chloroplast genomes, 216 SSRs, 143 pairs of long repeats, 571 SNPs, and 202 indels were detected. In addition, we identified seven hypervariable regions that can be used as potential molecular markers and DNA barcodes of Lilium through complete sequence alignment. The phylogenetic tree was constructed from the three chloroplast genome sequences of Lilium obtained here and 40 chloroplast genome sequences from the NCBI database (including 35 Lilium species, 4 Fritillaria species, and one species of Smilax). The analysis showed that the species clustering of the genus Lilium essentially conformed to the classical morphological classification system of Comber, but differences in the classification of individual species remained. In our report, we support the reclassification of Lilium henryi and Lilium rosthorniiy in the genus Lilium. In general, this study not only provides genome data for three Lilium species, but also provides a comparative analysis of the Lilium chloroplast genomes. These advances will help to identify Lilium species, clarify the phylogenetic analysis of the Lilium genus, and help to solve and improve the disputes and deficiencies in the traditional morphological classification.

More Income, Less Pollution? How Income Expectation Affects Pesticide Application.

Farmers are still the foundation of China's current "small, scattered, and weak" agricultural production pattern. As such, increasing guidance for reduction response behavior is central to reducing agricultural pesticide use. Following this pesticide reduction logic, four of the most widely promoted pesticide reduction technologies, including light trapping, biopesticide application, healthy crop growth, and insect-proof net technologies, were selected, and a theoretical analysis framework of farmers' willingness to adopt these technologies was constructed based on the theories of value perception and planned behavior. An ordered logistic regression model is used to explore key factors behind current pesticide reduction technology perceptions, technology response willingness, and behavioral decisions of farmers in China, with survey data from 516 farmers in Henan Province. The results show that among the four pesticide reduction technologies, healthy crop growth technology is the most-appealing one for farmers, followed by insect-proof net technology and biopesticide application technology. The least-appealing one for farmers is the light trapping technology. Farmers' perceived degree of income improvement from technology adoption is the main determinant of their willingness, which is positively significant at a 1% confidence level in all four models. In addition, farmers' willingness to respond to technologies is also significantly influenced by farmers' perception of technical operational ability, perception of risk from adopting technology, government-related subsidies, government technical training guidance, trust in government promotion of technology, and perception of the government's role in improving the external environment for adopting technology.

Understanding the Corrective Effect of the Urban Growth Boundary Policy on Land Finance Dependence of Local Governments in China.

The preference for land urbanization of local governments promotes urban sprawl, which leads to the dilemma of land finance dependence (LFD) of local governments and the negative constraints on the ecosystem of urban areas in China. However, how the urban growth boundary (UGB) policy corrects local governments' reliance on land finance has not been discussed in depth. In July 2014, the UGB policy began to be piloted in fourteen cities in China, providing a setting to further reveal the effectiveness of the UGB policy. By constructing an evolutionary game simulation model to clarify the behavioral strategies that local governments tend to adopt in the context of the UGB policy implementation, this study proves that the effective implementation of the UGB policy, by controlling the urban land capacity, can help solve local governments' LFD dilemma in China. The UGB policy consists of a set of technical means and policy tools that controls urban sprawl. It breaks the "unlimited land capacity" situation faced by local governments in China by limiting the urban land capacity within a given period of time, and has become a new solution to the dilemma of LFD. The implementation of the UGB policy highlighted the shortage of urban land, which has led to the increasing cost of land finance for local governments and constraints on local governments' LFD behavior. The shortage has also forced local governments to adjust and optimize their fiscal revenue structure. The UGB policy induced ongoing evolution in the benefit distribution among relevant entities in land finance, motivated local governments and other entities to adjust their primary strategies, and made it possible to address the dilemma of LFD in China.

Evaluating the Sustainable Land Use in Ecologically Fragile Regions: A Case Study of the Yellow River Basin in China.

How to realize the sustainable use of land resources is extremely important for environmental protection and sustainable development in ecologically fragile regions. Nevertheless, the logic of achieving sustainable land use (SLU) in ecologically fragile regions and the corrective mechanisms for the implementation of land use efficiency systems are not fully revealed in theory. The Yellow River Basin is an important ecological barrier in China, and it holds an important position in China's economic and social development, as well as for ecological safety. However, the basin is also ecologically vulnerable. Therefore, investigating eight central cities in the Yellow River Basin of China and using municipal-level panel data from 2009 to 2018, this paper constructs a multidimensional index system and is dedicated to carrying out a comprehensive evaluation of SLU and the diagnosis of obstacle factors in ecologically fragile regions. The study found the following: (1) From 2009 to 2018, the SLU level in the central cities of the Yellow River Basin evolved from the "Unsustainable Level" to the "Initial Sustainable Level" and then to the "Basic Sustainable Level". The overall development trend was positive, and the level of SLU also rose. (2) From 2009 to 2018, there was significant geographical variation in spatial disparities in SLU in the central cities of the Yellow River Basin. In 2018, the average comprehensive score of SLU showed a pattern of downstream > upstream > midstream. (3) The obstacle factors of SLU in the Yellow River Basin of these cities in 2009 were concentrated on resource and environmental sustainability, while those in 2018 were concentrated on social acceptability. (4) In terms of the transfer process of land use types in these Yellow River Basin cities, the transfer from cultivated land to other types of land use played a major role, while construction land showed a significant expansion over the past ten years.

Myeloid lineage contributes to pathological choroidal neovascularization formation via SOCS3.

BACKGROUND: Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. METHODS: We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. FINDINGS: SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. INTERPRETATION: These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. FUNDING: This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children's Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.

Normalization of non-canonical Wnt signalings does not compromise blood-brain barrier protection conferred by upregulating endothelial Wnt/ß-catenin signaling following ischemic stroke.

BACKGROUND: Endothelial canonical (Wnt/ß-catenin) and non-canonical Wnt signalings (Wnt/PCP and Wnt/Ca2+ ) promote blood-brain barrier (BBB) development and antagonize each other. However, the effects of ischemic stroke on endothelial canonical and non-canonical Wnt signalings are unclear. Further, how non-canonical Wnt signalings are influenced by upregulation of endothelial Wnt/ß-catenin signaling and subsequently affect BBB function following ischemic stroke have not been studied. METHODS: First, we determined the levels of Wnt signaling markers including TCF/LEF1 transcription activity, Axin2 mRNA, phospho-JNKThr183/Tyr185 , and NFAT in brain endothelial cells (ECs) with the deletion of Wnt receptor Frizzled (Fzd)4 or Fzd6, the two most abundant Fzds in brain ECs. Next, we observed the effect of ischemia/reperfusion injury on Wnt signalings in brain ECs and adult mice. Last, we assessed the changes of non-canonical Wnt signalings and BBB injury in the early stage of ischemic stroke in mice with endothelial ß-catenin activation (ß-cat mice). RESULTS: Fzd4 or Fzd6 deletion dampened both Wnt/ß-catenin and Wnt/PCP signalings but enhanced Wnt/Ca2+ signaling in brain ECs. Both canonical and non-canonical Wnt signalings in brain ECs were downregulated after ischemia/reperfusion injury in vitro and in vivo. Upregulating endothelial Wnt/ß-catenin signaling in ß-cat mice normalized the downregulated non-canonical Wnt signalings, which did not compromise its protective effects on BBB integrity and endothelial tight junction following ischemic stroke. CONCLUSIONS: The BBB protection induced by upregulation of endothelial Wnt/ß-catenin signaling may be not interfered by the normalization of non-canonical Wnt signalings in the early stage of ischemic stroke.

Apatinib inhibits gastric carcinoma development by regulating the expression levels of IL-17 via the Bax/Bcl-2 signaling pathway.

Gastric carcinoma is a common type of gastrointestinal tumor with high morbidity and mortality rates. IL-17 is a newly discovered cytokine that has been reported to serve an important role in the development of gastric carcinoma. The potential effect of apatinib on IL-17 expression levels in the development of gastric carcinoma has been rarely reported. The present study aimed to investigate the potential mechanism of IL-17 and apatinib in the development of gastric carcinoma. A total of 30 tumor and para-carcinoma tissues were collected from 30 patients with gastric carcinoma between January 2019 and December 2019 and the expression levels of IL-17 in the tissues were analyzed by reverse transcription-quantitative PCR and western blotting. An in vitro model of gastric carcinoma was also established using the HGC-27 cell line, in which the cells were divided into control, IL-17, IL-17-apatinib and apatinib groups. The expression levels of IL-17, Bax, Bcl-2 and caspase-3 were analyzed using reverse transcription-quantitative PCR and western blotting. An MTT assay and flow cytometry were used to analyze the proliferation and apoptosis of HGC-27 cells, respectively, and a Transwell assay was used to analyze the invasive ability of HGC-27 cells. The results revealed that the expression levels of IL-17 were significantly upregulated in the gastric carcinoma tissues compared with the para-carcinoma tissues. In vitro, IL-17 treatment promoted the proliferation and invasive ability of HGC-27 cells, but inhibited the apoptosis with the significantly downregulated expression levels of Bax and caspase-3 and the upregulated expression levels of Bcl-2 than control group. Conversely, apatinib treatment significantly inhibited the proliferative and invasive abilities of HGC-27 cells, but promoted cell apoptosis in the IL-17 and IL-17-apatinib groups.. Collectively, the present results suggested that the upregulation of IL-17 may be associated with the occurrence and development of gastric carcinoma. The findings indicated that apatinib may inhibit gastric carcinoma development by regulating IL-17 expression via the Bax/Bcl-2 signaling pathway. Therefore, the present findings may enhance the current knowledge of the effect of apatinib on gastric carcinoma cells.

Identification of Potential Hub Genes of Atherosclerosis Through Bioinformatic Analysis.

Cardiovascular and cerebrovascular diseases, which mainly consist of atherosclerosis (AS), are major causes of death. A great deal of research has been carried out to clarify the molecular mechanisms of AS. However, the etiology of AS remains poorly understood. To screen the potential genes of AS occurrence and development, GSE43292 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database in this study for bioinformatic analysis. First, GEO2R was used to identify differentially expressed genes (DEGs) and the functional annotation of DEGs was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Search Tool for the Retrieval of Interacting Genes (STRING) tool was used to construct the protein-protein interaction network and the most important modules and core genes were mined. The results show that a total of 211 DEGs are identified. The functional changes of DEGs are mainly associated with the cellular process, catalytic activity, and protein binding. Eighteen genes were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to actin. In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS.

Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene (PTPN12) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. METHODS: We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients' clinical data were analyzed. RESULTS: PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. CONCLUSION: The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.

Inhibitors of α-amylase and α-glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia.

The strategy of reducing carbohydrate digestibility by controlling the activity of two hydrolyzing enzymes (α-amylase and α-glucosidase) to control postprandial hyperglycemia is considered as a viable prophylactic treatment of type 2 diabetes mellitus (T2DM). Thus, the consumption of foods rich in hydrolyzing enzyme inhibitors is recommended for diet therapy of diabetes. Whole cereal products have gained increasing interests for plasma glucose-reducing effects. However, the mechanisms for whole cereal benefits in relation to T2DM are not yet fully understood, but most likely involve bioactive components. Cereal-derived phenolic compounds, peptides, nonstarch polysaccharides, and lipids have been shown to inhibit α-amylase and α-glucosidase activities. These hydrolyzing enzyme inhibitors seem to make whole cereals become nutritional strategies in managing postmeal glucose for T2DM. This review presents an updated overview on the effects provided by cereal-derived ingredients on carbohydrate digestibility. It suggests that there is some evidence for whole cereal intake to be beneficial in amelioration of T2DM through inhibiting α-glucosidase and α-amylase activities.

Targeting Neuroinflammation in Neovascular Retinal Diseases.

Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident microglia, retinal neurons have also been reported to contribute to inflammation, through inflammatory signals, which mediate blood vessel growth. Therefore, it is important to explore the detailed mechanisms of neuroinflammation's effects on retinal neovascularization. This review looks to summarize current research on the relationship between retinal angiogenesis and neuroinflammation in retinopathy, as well as the potential effects of neuroinflammation on retinal neovascularization in different animal models.

Whole barley prevents obesity and dyslipidemia without the involvement of the gut microbiota in germ free C57BL/6J obese mice.

Whole barley (WB) consumption is the subject of renewed interest because of its health benefits. However, there are still controversies regarding the mechanisms of the anti-obesity effects of WB. The gut microbiota has recently become a focus of research into obesity-related disorders. Therefore, the aim of this study was to investigate the contribution of the gut microbiota to the anti-obesity effects of WB. Germ-free (GF) C57BL/6J mice underwent gastric inoculation with human feces to obtain human flora-associated (HFA) mice, and then both the GF and HFA mice were fed a high fat diet (HFD) containing 46% WB or refined barley for 9 weeks. Features of obesity and dyslipidemia were compared between the GF and HFA mice and the cecal microbiota was analyzed using next-generation sequencing of microbial 16S rRNA. WB prevents obesity and hypercholesterolemia in the GF and HFA mice. The mechanism may include the inhibition of cholesterol synthesis, because sterol regulatory element-binding protein-1c (SREBP-1c) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) expression was downregulated, and a reduction in cholesterol accumulation, because cholesterol 7α-hydroxylase (CYP7A1) expression was upregulated, independent of the gut microbiota. Furthermore, WB intake enriched a variety of bacterial genera that are negatively associated with obesity, including Bacteroides, Parabacteroides, and Clostridium cluster XIVa, suggesting that WB counteracted gut dysbiosis in obese mice. Thus, WB helps prevent obesity and dyslipidemia via both gut microbiota-dependent and independent mechanisms.

MicroRNA-21 as a diagnostic marker for hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: MicroRNA-21 (miR-21) is one of the oncogenic miRNAs which may be a potential diagnostic biomarker for hepatocellular carcinoma (HCC). METHODS: We systematically searched Medline, Embase, the Cochrane Library, ISI Web of Knowledge, Scopus from inception to August 15, 2018, and reference lists of identified primary studies. Two independent investigators extracted patient and study characteristics. The sensitivity and specificity of microRNA-21 for HCC detection and were analyzed with a random effect model. The area under summary receiver operating characteristic curve (AUC) was used to estimate overall test performance. RESULTS: A total of 515 HCC patients, and 338 healthy or chronic hepatitis controls from six published studies were enrolled in this meta-analysis. All articles were published in English with moderate-to-high quality. The overall pooled sensitivity and specificity were 85.2% (73.3% to 88.4%) and 79.2% (68.4% to 87.0%), respectively. The AUC area was 0.89 (95% CI: 0.85-0.91). The studies had moderate heterogeneity (I2=70.11%). None of the subgroups investigated-ethnicity, controls, sample source-could account for the heterogeneity. CONCLUSION: MiR-21 is a helpful biomarker for early diagnosis of HCC. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, erological tests and imaging examinations for HCC surveillance.