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Background: Studies have shown that mitochondrial function and macrophages may play a role in the development of idiopathic pulmonary fibrosis (IPF). However, the understanding of the interactions and specific mechanisms between mitochondrial function and macrophages in pulmonary fibrosis is still very limited. Methods: To construct a prognostic model for IPF based on Macrophage- related genes (MaRGs) and Mitochondria-related genes (MitoRGs), differential analysis was performed to achieve differentially expressed genes (DEGs) between IPF and Control groups in the GSE28042 dataset. Then, MitoRGs, MaRGs and DEGs were overlapped to screen out the signature genes. The univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm were implemented to achieve key genes. Furthermore, the independent prognostic analysis was employed. The ingenuity pathway analysis (IPA) was employed to further understand the molecular mechanisms of key genes.Next, the immune infiltration analysis was implemented to identify differential immune cells between two risk subgroups. Results: There were 4791 DEGs between IPF and Control groups. Furthermore, 26 signature genes were achieved by the intersection processing. Three key genes including ALDH2, MCL1, and BCL2A1 were achieved, and the risk model based on the key genes was created. In addition, a nomogram for survival forecasting of IPF patients was created based on riskScore, Age, and Gender, and we found that key genes were associated with classical pathways including 'Apoptosis Signaling', 'PI3K/AKT Signaling', and so on. Next, two differential immune cells including Monocytes and CD8 T cells were identified between two risk subgroups. Moreover, we found that MIR29B2CHG and hsa-mir-1-3p could regulate the expression of ALDH2. Conclusion: We achieved 3 key genes including ALDH2, MCL1,, and BCL2A1 associated with IPF, providing a new theoretical basis for clinical treatment of IPF. [ABSTRACT FROM AUTHOR]

Background: Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. Results: The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. Conclusions: Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention. [ABSTRACT FROM AUTHOR]

Background and Aim: Autophagy and gut microbiota correlates closely with the inflammatory bowel disease. Herein, we aimed to study the roles of rapamycin on the gut microbiota in inflammatory bowel disease. Methods: Acute colitis was induced with dextran sodium sulfate (DSS) and 2,4,6‐trinitrobenzenesulfonic acid solution in mice. Mice were administered with rapamycin or hydroxychloroquine. Weight loss, disease activity index scores, histopathological score, serum inflammatory cytokines, intestinal permeability, and colonic autophagy‐related proteins were detected. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following the 16S DNA sequencing. The antibiotic cocktail‐induced microbiome depletion was performed to further investigate the relationship between autophagy activation and gut microbiota. Results: Compared with the control group, the colonic autophagy‐related proteins of P62, mTOR, and p‐mTOR increased significantly, while the levels of LC3B and ATG16L1 decreased (all P < 0.05) in the model group. After rapamycin intervention, the colonic pathology of mice improved, while the disease activity index score decreased substantially; the colon length increased, and the expression of IL‐6 and TNF‐α decreased. Following hydroxychloroquine treatment, some indicators suggested aggravation of colitis. Principal coordinates analysis showed that the DSS group was located on a separate branch from the rapamycin group but was closer to the hydroxychloroquine group. Compared with the DSS group, the rapamycin group was associated with higher abundances of f_Lactobacillaceae (P = 0.0151), f_Deferribacteraceae (P = 0.0290), g_Lactobacillus (P = 0.0151), g_Mucispirillum (P = 0.0137), s_Lactobacillus_reuteri (P = 0.0028), and s_Clostridium sp Culture_Jar‐13 (P = 0.0082) and a lower abundance of s_Bacteroides_sartorii (P = 0.0180). Linear discriminant analysis effect size showed that rapamycin increased the abundances of Lactobacillus‐reuteri, Prevotellaceae, Paraprevotella, Christensenella and Streptococcus and decreased those of Peptostreptococcaceae and Romboutsia Bacteroides‐sartorii. Besides, the improvement effect of autophagy activation on colitis disappears following gut microbiome depletion. Conclusion: The therapeutic effects of rapamycin on extenuating experimental colitis may be related to the gut microbiota. [ABSTRACT FROM AUTHOR]

Chinese Materia Medica Resources (CMMRs) are crucial for developing the tradition and industry of traditional Chinese medicine. Given the increasing demand for CMMRs, an accurate and effective understanding of CMMRs is urgently needed. Chinese medicinal plants (CMPs) are the most important sources of CMMRs. Traditional methods of investigating medicinal plant resources have limitations, including severe subjectivity and poor timeliness, which make it difficult to meet the demand for real-time monitoring of large-scale medicinal plant resources. In recent years, remote sensing technology has become an important means of obtaining information on medicinal plants, and the application of this technology has made up for the shortcomings of traditional methods. This paper first discusses the development of investigation methods of CMMRs; points out the importance of remote sensing technology in the application of spatial distribution and information identification and extraction of Chinese medicinal plant resources (CMPRs); analyzes the characteristics of CMPs in different planting patterns, different habitats, and different regions from the perspective of remote sensing information extraction; and explores the selection of suitable data sources, providing a reference for medicinal plant identification and information extraction. Secondly, according to the existing classification and identification methods, previous studies are summarized from the perspectives of classification scales, classification features, and classification accuracy, and the advantages and disadvantages of the commonly used remote sensing classification methods in the investigation of CMPRs are summarized and compared. Finally, the development trend of remote sensing technology in the identification and information extraction of CMPs is examined, and the key technical problems to be solved in the identification and classification of CMPs and the extraction of area information are summarized so as to provide technical support and experience references for the application of remote sensing in the investigation of CMPRs. [ABSTRACT FROM AUTHOR]

Background and Aim: Mucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y‐box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution. Methods: We studied the characteristics of UXT‐V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT‐V1 in the colonic epithelium was investigated using lentivirus‐mediated shRNA in vitro and ex vivo. Through endogenous Co‐immunoprecipitation and LC–MS/MS, we identified ZONAB as a UXT‐V1‐interactive protein. Results: Herein, we report that UXT‐V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT‐V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT‐V1 in NCM‐460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT‐V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT‐V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation‐related genes, including AML1 and KLF4. Conclusion: Taken together, our study reveals a potential role of UXT‐V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC. [ABSTRACT FROM AUTHOR]

Crop-distribution information constitutes the premise of precise management for crop cultivation. Euclidean distance and spectral angle mapper algorithms (ED and SAM) mostly use the spectral similarity and difference metric (SSDM) to determine the spectral variance associated with the spatial location for crop distribution acquisition. These methods are relatively insensitive to spectral shape or amplitude variation and must reconstruct a reference curve representing the entire class, possibly resulting in notable indeterminacy in the ultimate results. Few studies utilize these methods to compute the spectral variance associated with time and to define a new index for crop identification—namely, the spectral variance at key stages (SVKS)—even though this temporal spectral characteristic could be helpful for crop identification. To integrate the advantages of sensibility and avoid reconstructing the reference curve, an object self-reference combined algorithm comprising ED and SAM (CES) was proposed to compute SVKS. To objectively validate the crop-identification capability of SVKS-CES (SVKS computed via CES), SVKS-ED (SVKS computed via ED), SVKS-SAM (SVKS computed via SAM), and five spectral index (SI) types were selected for comparison in an example of maize identification. The results indicated that SVKS-CES ranges can characterize greater interclass spectral separability and attained better identification accuracy compared to other identification indexes. In particular, SVKS-CES2 provided the greatest interclass spectral separability and the best PA (92.73%), UA (100.00%), and OA (98.30%) in maize identification. Compared to the performance of the SI, SVKS attained greater interclass spectral separability, but more non-maize fields were incorrectly identified as maize fields via SVKS usage. Owning to the accuracy-improvement capability of SVKS-CES, the omission and commission errors were obviously reduced via the combined utilization of SVKS-CES and SI. The findings suggest that SVKS-CES application is expected to further spread in crop identification. [ABSTRACT FROM AUTHOR]

As the core component of wearable electronic devices, flexible energy storage materials play an irreplaceable role. At present, it is still a challenge to prepare flexible electrode materials with high energy density. In this paper, a polyaniline‐based composite flexible conductive hydrogel (PPG‐P) with a two‐level conductive network is successfully prepared by a secondary induced assembly in situ polymerization method. The special conductive structure greatly promotes the efficiency of charge transfer and the utilization of electroactive substances, so that PPG‐P exhibits excellent electrochemical performance. In a three‐electrode system, PPG‐P has a mass‐specific capacitance as high as 989 F g−1 (0.5 A g−1). After 1000 charge and discharge cycles, the capacitance retention is 87%. Symmetrical flexible supercapacitors based on PPG‐P have high specific capacitance (176 F g−1/0.5 A g−1) and high energy density (15.6 Wh kg−1). After 1000 cycles of constant current charge and discharge, the capacitance maintains 78.1%. The preparation of PPG‐P with a hierarchical structure demonstrates the possibility of achieving high energy density in flexible electrode materials, which has great application potential in the development of energy storage elements in wearable devices. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is a devasting disease of which mortality almost parallels its incidence. PC tissue may express aberrantly methylated neuronal pentraxin II (NPTX2), but it is unclear what the consequences of this are. Methods: We systematically searched PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), from inception to July 15, 2020, to identify if the detection of methylated NPTX2 have sufficient sensitivity and specificity to identify PC from other benign pancreatic diseases. Results: Majority of the studies obtained samples from pancreatic juice by endoscopy or surgery and composed of population with chronic pancreatitis, benign cystic lesion, intraductal papillary mucinous neoplasm, and healthy controls. Our results demonstrated that the diagnostic value of methylated NPTX2 is of widely various sensitivity and specificity and it shown higher specificity in differentiate PC from benign diseases. The lab method of quantitative real‐time methylation‐specific PCR (QMSP) has higher specificity than real‐time methylation‐specific PCR (MSP) in detecting the indicator. Conclusions: NPTX2 methylation could serve as a promising molecular biomarker for pancreatic cancer diagnosis, for its high diagnostic value in differentiating pancreatic cancer from benign pancreatic disease with the lab method. The variable sensitivity of methylated NPTX2 was multifactorial, and it must be promoted before applied as screening test in clinical practice. Furthermore, experiments on methylated NPTX2 were needed to expanded for lower the heterogeneity. [ABSTRACT FROM AUTHOR]

Background and Aim: We comprehensively carry out a systematic review and meta‐analysis of previous studies to determine the association between intestinal Faecalibacterium prausnitzii (F. prausnitzii) and inflammatory bowel disease (IBD) in human studies. Methods: A systematic literature search of PubMed, Embase, and the Cochrane Library database was conducted until April 1, 2020. Inclusion criteria were studies involving patients with Crohn's disease (CD) or ulcerative colitis (UC) with abundance of F. prausnitzii. The quality of the studies was assessed by the modified Newcastle–Ottawa scale. Results: A total of 1669 subjects (427 CD patients, 560 UC patients, and 682 healthy controls) were enrolled from 16 studies. Both CD (standardized mean difference [SMD]: −1.36; 95% CI, −1.74 to −0.98; P < 0.00001) and UC patients (SMD: −0.81; 95% CI, −1.21 to −0.42; P < 0.0001) had a lower abundance of F. prausnitzii than the healthy controls. Compared with the IBD remission patients, the IBD active patients had lower levels of F. prausnitzii (SMD: ‐0.56; 95% CI, −0.91 to −0.21; P = 0.002). In the subgroup analyses, the abundance of F. prausnitzii was reduced in both active CD patients (SMD: −0.78; 95% CI, −1.51 to −0.04; P = 0.04) and active UC patients (SMD:−0.44; 95%CI, −0.81 to −0.07; P = 0.02) when compared with the patients with CD or UC in remission, respectively. Conclusion: A negative association between abundance of F. prausnitzii and IBD activity is observed, but a cut‐off level of F. prausnitzii to diagnose and/or to start treating IBD is not determined. [ABSTRACT FROM AUTHOR]

Acquired immune deficiency syndrome, caused by the human immunodeficiency virus (HIV), has been associated with intestinal dysbiosis, which includes an increase in the number of mucosa-associated pathobionts. In the present study, the intestinal mucosal microbiota patterns of HIV-infected patients were compared with those of healthy individuals in a population from Guangzhou, China. The gut microbiota of intestinal mucosal samples from 12 patients with HIV (transmission routes included sex and intravenous drug abuse) was compared with that of 12 healthy age- and sex-matched controls. Gut microbial communities were profiled via sequencing of the bacterial 16S ribosomal RNA genes. Dysbiosis in HIV-infected individuals was characterized by decreased α-diversity, decreased levels of Firmicutes and increased levels of Proteobacteria. Furthermore, low mean counts of Lachnoclostridium, Roseburia, Thauera, Dorea and Roseburia inulinivorans, and high mean counts of Halomonas and Shewanella bacteria, were indicated to be HIV-associated mucosal bacterial alterations. The relative abundance of Fusobacterium and Lachnoclostridium was significantly decreased, while that of Halomonas and Shewanella was significantly increased in patients with sexually transmitted HIV-infection compared with healthy controls. Alterations of the gut microbiota during HIV infection were also indicated to be associated with the route of HIV transmission. Certain bacteria may be potential biomarkers for HIV infection in patients from Guangzhou, China. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the underlying mechanisms of diabetic retinopathy (DR) development. Methods: Real-Time qPCR was used to detect Casein kinase 2 interacting protein-1 (CKIP-1) and Nuclear factor E2-related factor 2 (Nrf2) mRNA levels. Western Blot was employed to detect protein levels. Malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) kit and glutathione peroxidase (GSH-Px) kit were used to evaluate oxidative stress in high-glucose treated human retinal endothelial cells (HRECs). Calcein-AM/propidium iodide (PI) double stain kit was employed to detect cell apoptosis. Enzyme-linked ImmunoSorbent Assay (ELISA) was used to detect inflammation associated cytokines secretion. Co-immunoprecipitation (CO-IP) was performed to investigate the interactions between CKIP-1 and Nrf2. Luciferase reporter gene system was used to detect the transcriptional activity of Nrf2. Results: CKIP-1 was significantly downregulated in either DR tissues or high-glucose treated HRECs comparing to the Control groups. Besides, high-glucose (25 mM) inhibited HRECs viability and induced oxidative stress, inflammation associated cytokines (TNF-α, IL-6 and IL-1β) secretion and cell apoptosis, which were all reversed by synergistically overexpressing CKIP-1 and aggravated by knocking down CKIP-1. Of note, we found that overexpressed CKIP-1 activated Nrf2/ARE signaling pathway and increased its downstream targets including HO-1, NQO-1, γGCS and SOD in high-glucose treated HRECs. Further results also showed that CKIP-1 regulated cell viability, oxidative stress, inflammation and apoptosis in high-glucose treated HRECs by activating Nrf2/ARE signaling pathway. Conclusion: We concluded that overexpressed CKIP-1 alleviated DR progression by activating Nrf2/ARE signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms., Methods: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays., Results: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro., Conclusions: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD., (© 2024. The Author(s).)

Background: Paraclostridium bifermentans is the most diverse distributed species of Paraclostridium and can cause fatal human infections under rare conditions. However, its pathogenic mechanisms and adaptation ability behind infections remain unclear. Herein, we reported the complete genome sequence of P. bifermentans HD0315&#95;2 isolated from the feces of a patient with Crohn's disease. Then, we performed genomic analyses to understand its pathogenic mechanisms and adaptation ability., Results: The de novo assembly revealed that the HD0315&#95;2 strain carried a circular chromosome of 3.27 Mb and six circular plasmids (19.41 to 139.50 kb). The phylogenomic analysis assigned the HD0315&#95;2 strain as P. bifermentans and reclassified some previously non- P. bifermentans strains into this clade. The general genomic features showed that this species harbored a flexible genomic pool characterized by variable genome length and multiple plasmids. Then, the HD0315&#95;2 strain was predicted as a human pathogen with high probability, and Listeria LIPI-1 virulence proteins were identified on its genome. Besides, abundant antibiotics/metal/stress resistant genes, such as asrABCH, cat, mccF, macB, entS, albA, bcrA , and tetB , were carried by either the genome or the plasmids. Furthermore, we proposed that transposase-directed horizontal gene transfer was responsible for the distribution of multiple copies of the hin gene in the plasmids., Conclusion: The flexible genomic pool of P. bifermentans encodes abundant functions for antimicrobial or oxidative stress resistance, helping it successfully inhabit and adapt to diverse environments. Moreover, P. bifermentans HD0315&#95;2 might infect hosts via a Listeria LIPI-1-like cycle, with the help of a plasmid expressing the Hin DNA invertase to evade host immune responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Wang, Peng, Cai, Liu, Huang, Huang and Nie.)

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by relapse and remission alternately. It remains a great challenge to diagnose and assess disease activity during IBD due to the lack of specific markers. While traditional biomarkers from plasma and stool, such as C-reactive protein (CRP), fecal calprotectin (FC), and S100A12, can be used to measure inflammation, they are not specific to IBD and difficult to determine an effective cut-off value. There is consensus that gut microbiota is crucial for intestinal dysbiosis is closely associated with IBD etiopathology and pathogenesis. Multiple studies have documented differences in the composition of gut microbiota between patients with IBD and healthy individuals, particularly regarding microbial diversity and relative abundance of specific bacteria. Patients with IBD have higher levels of Proteobacteria and lower amounts of Bacteroides, Eubacterium , and Faecalibacterium than healthy individuals. This review summarizes the pros and cons of using traditional and microbiota biomarkers to assess disease severity and treatment outcomes and addresses the possibility of using microbiota-focused interventions during IBD treatment. Understanding the role of microbial biomarkers in the assessment of disease activity and treatment outcomes has the potential to change clinical practice and lead to the development of more personalized therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Huang, Xu, Xu, Liu, Zhao, Wang, Huang, Peng, Chen, Nie, Zhou and Zhou.)

Gut microbiota has a strong influence on the onset and development of systemic lupus erythematosus (SLE), and several studies have demonstrated the effectiveness of microbiota-derived butyrate to ameliorate SLE. However, the roles of butyrate on gut microbiota in SLE are not understood. Using MRL/lpr lupus-prone mice, we examined gut microbiota profiles after butyrate treatment by 16S rRNA sequencing. Alterations in intestinal microbiome in mice with lupus-like disease were mainly characterized by a reduction in microbial diversity, with an increased abundance of Bacteroidetes and a decrease of Firmicutes. Treatment of lupus-prone mice with butyrate resulted in increased abundance of Firmicutes ( P = 0.003), Clostridia ( P = 0.005), Clostridiales ( P = 0.005), Lachnospiraceae ( P = 0.009), Ruminococcaceae ( P = 0.021), Peptostreptococcaceae ( P = 0.021), Ruminiclostridium ( P = 0.016), Oscillibacter ( P = 0.048), Romboutsia ( P = 0.025), Lachnoclostridium ( P = 0.012), Coprococcus ( P = 0.015), Ruminococcus ( P = 0.011), Clostridium leptum ( P < 0.05), and Dorea&#95;spp . ( P = 0.019), and a reduced proportion of Bacteroidetes ( P = 0.004), Bacteroidia ( P = 0.004), and Bacteroidales ( P = 0.004). Further, butyrate supplementation could ameliorate kidney damage. Overall, this study suggests that gut microbiota alterations occur in MRL/lpr lupus-prone mice following treatment with butyrate. Butyrate supplementation ameliorated gut microbiota dysbiosis. These findings support the use of butyrate and butyrate-producing bacteria as potential treatments for SLE., (Copyright © 2020 He, Xu, Xu, Zhao, Lin, Zhou and Nie.)

Purpose: The aim of this study was to investigate the underlying mechanisms of diabetic retinopathy (DR) development., Methods: Real-Time qPCR was used to detect Casein kinase 2 interacting protein - 1 ( CKIP - 1 ) and Nuclear factor E2 - related factor 2 ( Nrf2 ) mRNA levels. Western Blot was employed to detect protein levels. Malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) kit and glutathione peroxidase (GSH-Px) kit were used to evaluate oxidative stress in high-glucose treated human retinal endothelial cells (HRECs). Calcein-AM/propidium iodide (PI) double stain kit was employed to detect cell apoptosis. Enzyme-linked ImmunoSorbent Assay (ELISA) was used to detect inflammation associated cytokines secretion. Co-immunoprecipitation (CO-IP) was performed to investigate the interactions between CKIP - 1 and Nrf2 . Luciferase reporter gene system was used to detect the transcriptional activity of Nrf2 ., Results: CKIP - 1 was significantly downregulated in either DR tissues or high-glucose treated HRECs comparing to the Control groups. Besides, high-glucose (25 mM) inhibited HRECs viability and induced oxidative stress, inflammation associated cytokines (TNF-α, IL-6 and IL-1β) secretion and cell apoptosis, which were all reversed by synergistically overexpressing CKIP - 1 and aggravated by knocking down CKIP - 1 . Of note, we found that overexpressed CKIP - 1 activated Nrf2 / ARE signaling pathway and increased its downstream targets including HO - 1 , NQO - 1 , γGCS and SOD in high-glucose treated HRECs. Further results also showed that CKIP - 1 regulated cell viability, oxidative stress, inflammation and apoptosis in high-glucose treated HRECs by activating Nrf2 / ARE signaling pathway., Conclusion: We concluded that overexpressed CKIP - 1 alleviated DR progression by activating Nrf2 / ARE signaling pathway., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Oxidative stress serves a vital function in the pathogenesis of age‑related macular degeneration (AMD); genipin (GP) possesses antioxidative properties. The present study aimed to investigate the effects of GP on retinal pigment epithelial (RPE) cells induced by H2O2 and the underlying mechanism. ARPE‑19 cells were subjected to H2O2 treatment to induce oxidative damage. Cell viability was determined via an MTT assay. Reactive oxygen species (ROS) levels and cell apoptosis were detected by flow cytometry. Nuclear factor‑erythroid 2‑related factor‑2 (Nrf2) signaling‑associated and the expression of apoptosis‑associated factors were measured using reverse transcription‑quantitative polymerase chain reaction assay and western blotting. The results revealed that 200 µM H2O2 and 30 µM GP were determined to be the optimal concentrations for subsequent experimentation. GP reversed the inhibitory effects of H2O2 by promoting cell viability, attenuating ROS accumulation and cell apoptosis, and increased the expression of Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H: Quinine oxidoreductase 1 (NQO1); Nrf2 silencing inhibited HO‑1 and NQO1 expression. In addition, Nrf2 silencing enhanced the effects of H2O2 by promoting ROS production and cell apoptosis. Compared with H2O2, Nrf2 silencing further decreased the expression levels of B‑cell lymphoma‑2 (Bcl‑2), but increased that of Bcl‑2‑associated X protein and cleaved‑caspase‑3. The results of the present study revealed that Nrf2 silencing attenuated the protective effects of GP on H2O2‑induced injury in ARPE‑19 cells by promoting apoptosis and oxidation. Collectively, GP attenuated oxidative damage induced by H2O2 in ARPE‑19 cells. Furthermore, the molecular mechanism may be associated with the Nrf2 signaling pathway. The findings of the present study nay provide insight into a potential therapeutic agent for the treatment of AMD.

BACKGROUND The purpose of this study was to analyze tear inflammatory cytokines of different subclasses of dry eye disease (DED) patients using Luminex technology. MATERIAL AND METHODS Forty-five DED patients including 20 Sjogren syndrome aqueous tear deficiency (SS-ATD) patients, 20 non-Sjogren syndrome aqueous tear deficiency (NSS-ATD) patients, 15 meibomian gland dysfunction (MGD) patients, and 15 normal participants were enrolled in this study. Concentrations of 11 inflammatory cytokines in tear samples of study participants were measured by Luminex assay; ELISA assay was further applied for validation. RESULTS The levels of cytokines were mostly increased (TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-12 P70, IL-13, IFN-γ, and MIP-1α) in DED patients compared with normal participants. And the levels of TNF-α, IL-6, IL-8, and IL-12P70 were significantly elevated in tears of the patient groups compared to tears of participants in the normal group (P<0.05). Statistical differences were also observed among the patient groups (SS-ATD, NSS-ATD, and MGD) for the level of IL-8 and TNF-α. The results of ELISA assay demonstrated the consistence with Luminex assay, confirming the practicality of Luminex technology for the analysis of multiple cytokines in DED patient tears. CONCLUSIONS The levels of inflammatory cytokines were mostly elevated in DED patients, and statistical differences of some cytokines were also found between SS-ATD, NSS-ATD, and MGD groups, suggesting that inflammatory cytokines could be potential supplements for the diagnosis of DED subclasses and therapeutic targets for DED patients.

Homeobox genes (HOX genes) have been implicated in many tumors. As a member of HOX genes, HOXB5 is overexpressed in bladder cancer and contributes to the proliferation and invasion of breast cancer cells. However, functions of HOXB5 in retinoblastoma remain elusive. In this study, we found that HOXB5 expression is upregulated in retinoblastoma cell lines and tissues. Overexpression of HOXB5 promoted retinoblastoma cell migration and invasion, but knockdown of HOXB5 suppressed the migration and invasion. Moreover, HOXB5 induced the activation of ERK1/2 and upregulated the production of MMP-3 and MMP-13. In addition, ERK1/2 pathway was required for HOXB5-mediated retinoblastoma cell migration and invasion. Taken together, our study suggests that HOXB5 promotes the migration and invasion of retinoblastoma cells by inducing the activation of ERK1/2 and increasing the production of MMP-3 and MMP-13. Therefore, HOXB5 may represent an effective target for treatment of retinoblastoma., Competing Interests: None.

Background: Diabetic retinopathy (DR) is one of the most important complications of diabetes mellitus (DM) and is the leading cause of blindness in diabetic patients. Recent studies showed that as important inflammatory mediators, high mobility group box 1 (HMGB-1) is associated with diabetic peripheral neuropathy and can participate in the occurrence and development of DR. This study explored HMGB-1 as a therapeutic target for DR treatment through observing its role in retinal ganglion cells (GRCs) in a high glucose environment., Material and Methods: RGCs were randomly divided into 3 groups: the normal control group, the high glucose group, and the siRNA HMGB-1 group. Real-time PCR was used to detect HMGB-1 mRNA expression. ELISA was used to test HMGB-1 protein expression in the supernatant. MTT assay was performed to determine cell proliferation. Real-time PCR and Western blotting were used to analyze TLR4 and NF-κB expression., Results: HMGB-1 mRNA was up-regulated (P=0.015) and protein secretion increased (P=0.022) in the high glucose environment. RGCs survival decreased (P=0.026), while TLR4 and NF-κB mRNA (P=0.009 and P=0.017, respectively) and protein expression increased significantly (P=0.041 and P=0.024, respectively). SiRNA HMGB-1 transfection obviously inhibited HMGB-1 mRNA expression (P=0.032), reduced HMGB-1 secretion (P=0.012), and decreased TLR4 and NF-κB mRNA (P=0.033 and P=0.024, respectively) and protein expression (P=0.032; P=0.027, respectively). Compared with the high glucose group, the RGCs survival rate increased significantly (P=0.037)., Conclusions: As a therapeutic target, HMGB-1 can inhibit inflammation and promote RGCs survival to delay DR progress through the HMGB-1-TLR4-NF-κB signaling pathway.