A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

Clinical factors for delayed neuropsychiatric sequelae from acute carbon monoxide poisoning: a retrospective study.

Background: Delayed neuropsychiatric sequelae (DNS), which seriously affect the daily lives of patients, are the most common complications of carbon monoxide (CO) poisoning. No uniform screening tool is available for identifying high-risk groups. Therefore, in this study, we aimed to explore whether conventional laboratory indicators and imaging data from primary hospitals could predict the occurrence of DNS. Methods: This retrospective observational study was conducted in a single-center primary hospital from January 1, 2021 to May 31, 2023. Participants included patients aged >18 years with acute CO poisoning. Patients with complete recovery in the acute phase were followed up by telephone and outpatient visits, and the presence of DNS was determined according to the occurrence of new neurological symptoms within 6 weeks after discharge. We obtained demographic, laboratory, and imaging data from the medical records and performed a univariate analysis. A multivariate logistic regression model was used to identify independent clinical predictors of DNS. Results: A total of 73 patients were included in the study, of whom 25 (34.2%) developed DNS. Multivariate logistic regression analysis revealed that a longer duration of CO exposure (adjusted odds ratio (AOR): 1.262, 95% confidence interval (CI): 1.069-1.490) and the presence of acute brain lesions on diffusion-weighted imaging (DWI) (AOR: 5.117, 95% CI: 1.430-18.315) were independent risk factors for DNS. Receiver operating characteristic analyses of the duration of CO exposure were performed (area under the curve (AUC): 0.825; 95% CI: 0.731-0.918) with a cut-off value of 5.5 h, and DNS was predicted with a sensitivity of 96% and a specificity of 66.7%. Conclusion: High cranial DWI signal within 24 h and duration of poisoning longer than 5.5 h are independent predictors of DNS. The predictive effects of conventional laboratory indicators require further standardized and large-sample studies.

Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial.

BACKGROUND: Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. METHODS: We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. FINDINGS: Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. INTERPRETATION: The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. FUNDING: National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

CT Features of Recurrent Acute Pancreatitis: Early Phase Versus Late Phase.

OBJECTIVES: The aim of this study was to investigate the computed tomography (CT) features of recurrent acute pancreatitis (RAP) in the early phase and late phase. METHODS: Recurrent acute pancreatitis data were obtained over the past 5 years. Recurrent acute pancreatitis patients were divided into 2 groups according to the time from RAP onset to performing CT examination: the early phase (first week) and late phase (after the first week) based on the 2012 revised Atlanta classification (RAC). Evaluation and comparison of patients' demographic data, RAC, CT findings, CT severity index (CTSI) score, and extrapancreatic inflammation on CT (EPIC) score were conducted in the 2 groups. RESULTS: Hypertriglyceridemia was the most common cause of RAP in 679 of 686 patients (positive CT rate: 98.98%). Among 679 CT-positive patients, interstitial edematous pancreatitis and necrotizing pancreatitis accounted for 61.71% (419/679) and 38.29% (260/679), respectively. The CTSI and EPIC scores were higher in the late phase than in the early phase (both P 's < 0.05). The proportion of moderately severe and severe RAP patients based on RAC was higher in the late phase than in the early phase ( P < 0.05). Early-stage EPIC score was more accurate than CTSI and Acute Physiology and Chronic Health Evaluation (APACHE) II scores in predicting clinically severe RAP (EPIC vs CTSI; EPIC vs APACHE II, both P 's < 0.05). CONCLUSIONS: Recurrent acute pancreatitis is more severe in the late phase than in the early phase. The EPIC score is more indicative of clinically severe RAP than CTSI and APACHE II scores in the early phase of RAP.

Research progress on cardiac tissue construction of mesenchymal stem cells for myocardial infarction.

Heart failure is still the main complication affecting the prognosis of acute myocardial infarction (AMI), and mesenchymal stem cells (MSCs) are an effective treatment to replace necrotic myocardium and improve cardiac functioning. However, the transplant survival rate of MSCs still presents challenges. In this review, the biological characteristics of MSCs, the progress of mechanism research in the treatment of myocardial infarction, and the advances in improving the transplant survival rate of MSCs in the replacement of necrotic myocardial infarction are systematically described. From a basic to advanced clinical research, MSC transplants have evolved from a pure injection, an exosome injection, the genetic modification of MSCs prior to injection to the cardiac tissue engineering of MSC patch grafting. This study shows that MSCs have wide clinical applications in the treatment of AMI, suggesting improved myocardial tissue creation. A broader clinical application prospect will be explored and developed to improve the survival rate of MSC transplants and myocardial vascularization.

Intronic microRNA-directed regulation of mitochondrial reactive oxygen species enhances plant stress tolerance in Arabidopsis.

MicroRNAs (miRNAs) play crucial roles in regulating plant development and stress responses. However, the functions and mechanism of intronic miRNAs in plants are poorly understood. This study reports a stress-responsive RNA splicing mechanism for intronic miR400 production, whereby miR400 modulates reactive oxygen species (ROS) accumulation and improves plant tolerance by downregulating its target expression. To monitor the intron splicing events, we used an intronic miR400 splicing-dependent luciferase transgenic line. Luciferase activity was observed to decrease after high cadmium concentration treatment due to the retention of the miR400-containing intron, which inhibited the production of mature miR400. Furthermore, we demonstrated that under Cd treatments, Pentatricopeptide Repeat Protein 1 (PPR1), the target of miR400, acts as a positive regulator by inducing ROS accumulation. Ppr1 mutation affected the Complex III activity in the electron transport chain and RNA editing of the mitochondrial gene ccmB. This study illustrates intron splicing as a key step in intronic miR400 production and highlights the function of intronic miRNAs as a 'signal transducer' in enhancing plant stress tolerance.

Small bowel perforation caused by thermal injury during colonic polypectomy: A case report and literature review.

RATIONALE: Iatrogenic gastrointestinal perforation is a known uncommon complication of colonoscopy. The perforation usually occurs in the colon itself. Rarely, colonoscopic procedures can also cause the perforations of the small intestine. PATIENT CONCERNS AND DIAGNOSES: We describe the case of a 70-year-old man who experienced abdominal pain several hours after electrical polypectomy in the transverse colon. Urgent abdominal computed tomography scans showed a few bubbles on the frontal surface around the liver and a little extraluminal free air in the upper abdomen. Urgent exploratory laparotomy revealed a round perforation with a diameter of approximately 5 mm in the ileum 80 cm proximal to the ileocecal valve, accompanied by the outflow of intestinal contents. A small bowel perforation by thermal injury was diagnosed during colonic polypectomy. INTERVENTIONS AND OUTCOMES: The ileal perforation was repaired primarily after debridement of the perforation site and abdominal cavity. The patient recovered well after surgery. Histopathological examination of the perforation site demonstrated inflammatory necrosis and infiltration of inflammatory cells. LESSONS: Small bowel perforation should be considered after colonoscopic procedures although the incidence is exceedingly rare. Urgent exploratory laparotomy is warranted when a visceral perforation is identified after colonoscopy.

Submucosal protuberance caused by a fish bone in the absence of preoperative positive signs: A case report.

BACKGROUND: Submucosal protuberance caused by fish bone insertion into the digestive tract has rarely been reported. These cases usually include patients with clear signs such as a history of fish intake, pain, and dysphagia, as well as positive findings on endoscopy and imaging. Here, we report a case of a fish bone hidden in the submucosal protuberance of the gastric antrum during endoscopic submucosal dissection without preoperative obvious positive signs. CASE SUMMARY: A 58-year-old woman presented with epigastric pain for the past 20 d and a submucosal protuberance. Abdominal computed tomography and endoscopic ultrasonography did not indicate the presence of a fish bone. We assumed the cause to be an ordinary submucosal eminence and performed an endoscopic submucosal dissection to confirm its essence. During the operation, a fish bone approximately 20 mm in length was found incidentally. CONCLUSION: Our report could potentially prevent the oversight of embedded fish bones and associated adverse effects in patients with similar presentation.

Salt responsive alternative splicing of a RING finger E3 ligase modulates the salt stress tolerance by fine-tuning the balance of COP9 signalosome subunit 5A.

Increasing evidence points to the tight relationship between alternative splicing (AS) and the salt stress response in plants. However, the mechanisms linking these two phenomena remain unclear. In this study, we have found that Salt-Responsive Alternatively Spliced gene 1 (SRAS1), encoding a RING-Type E3 ligase, generates two splicing variants: SRAS1.1 and SRAS1.2, which exhibit opposing responses to salt stress. The salt stress-responsive AS event resulted in greater accumulation of SRAS1.1 and a lower level of SRAS1.2. Comprehensive phenotype analysis showed that overexpression of SRAS1.1 made the plants more tolerant to salt stress, whereas overexpression of SRAS1.2 made them more sensitive. In addition, we successfully identified the COP9 signalosome 5A (CSN5A) as the target of SRAS1. CSN5A is an essential player in the regulation of plant development and stress. The full-length SRAS1.1 promoted degradation of CSN5A by the 26S proteasome. By contrast, SRAS1.2 protected CSN5A by competing with SRAS1.1 on the same binding site. Thus, the salt stress-triggered AS controls the ratio of SRAS1.1/SRAS1.2 and switches on and off the degradation of CSN5A to balance the plant development and salt tolerance. Together, these results provide insights that salt-responsive AS acts as post-transcriptional regulation in mediating the function of E3 ligase.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Associated With Area Postrema Syndrome: A Case Report.

Glial fibrillary acidic protein astrocytopathy is an immunotherapy-responsive autoimmune disease of the central nervous system with various clinical manifestations; among these, there are few reports about area postrema syndrome (APS). The authors present the case of a female patient admitted to the hospital with intractable nausea and vomiting as the predominant symptom. The patient's cerebrospinal fluid was tested by cell-based assays (CBA) and found positive for the presence of anti-glial fibrillary acidic protein (GFAP) antibody, in addition, serological testing showed elevated levels of thyroglobulin and thyroperoxidase-specific antibodies. Brain and cervical MRI showed abnormally high signal on the T2 sequence in the dorsal medulla oblongata and right pontine arm. Therefore, the patient was diagnosed with autoimmune GFAP astrocytopathy. The symptoms improved rapidly after treatment with corticosteroids, and no recurrence has been observed thus far. APS may be a relatively rare clinical manifestation of GFAP astrocytopathy. Importantly, such presentation is challenging to correctly diagnose without typical MRI imaging findings. However, the detection of antibodies in the cerebrospinal fluid or serum may be valuable. Systemic and neurological autoimmunity often coexist, comprehensive antibody screening should be conducted.

Magnetic Resonance Imaging-Based Radiomics Models to Predict Early Extrapancreatic Necrosis in Acute Pancreatitis.

OBJECTIVE: The aim of the study was to investigate radiomics models based on magnetic resonance imaging (MRI) for predicting early extrapancreatic necrosis (EXPN) in acute pancreatitis. METHODS: Radiomics features were extracted from T2-weighted images of extrapancreatic collections and late arterial-phase images of the pancreatic parenchyma for 135 enrolled patients (94 in the primary cohort, including 47 EXPN patients and 41 in the validation cohort, including 20 EXPN patients). The optimal features after dimension reduction were used for radiomics modeling through a support vector machine. A clinical model, the MR severity index score, and extrapancreatic inflammation on MRI were evaluated. RESULTS: Twelve optimal features from the extrapancreatic collection images and 10 from the pancreatic parenchyma images were selected for modeling. The pancreatic parenchyma-based and extrapancreatic collection-based radiomics models showed good predictive accuracy in both the training and validation cohorts. The areas under the curve of the extrapancreatic collection-based radiomics model (0.969 and 0.976) were consistent with those of the pancreatic parenchyma-based model (0.931 and 0.921) for both cohorts and better than those of the clinical model and imaging scores for both cohorts. CONCLUSIONS: The MRI-based radiomics models of both the extrapancreatic collections and the pancreatic parenchyma had excellent predictive performance for early EXPN.

Acute Pancreatitis in Patients With a Medical History of Type 2 Diabetes Mellitus: Clinical Findings and Magnetic Resonance Imaging Characteristics.

OBJECTIVE: To determine the characteristics of type 2 diabetes mellitus (T2DM)-related acute pancreatitis (AP) on magnetic resonance imaging (MRI). METHODS: Retrospectively studied 262 patients with AP were admitted to our institution and underwent MRI. Diagnosis of T2DM-related AP was based on clinical manifestations, laboratory tests, and MRI. Pancreatic/peripancreatic changes were assessed on MRI. RESULTS: Fifty-three (20.2%) patients with T2DM-related AP and 209 (79.8%) with nondiabetic AP were enrolled. On MRI, a higher prevalence of necrotizing pancreatitis (P < 0.001), pancreatic necrosis >30% (57.5% vs 29.2%; P = 0.006), hemorrhage (35.8% vs 19.1%; P = 0.009), abdominal wall edema (67.9% vs 46.8%; P = 0.006), walled-off necrosis (43.2% vs 14.6%; P < 0.001), and infected collections (P < 0.001) were registered in T2DM with AP. T2DM-related AP sustained greater magnetic resonance severity index (mean, 5.1 [range, 2-10] vs 3.4 [range, 1-10]; P < 0.001), higher incidence of moderate and severe pancreatitis (69.8% vs 40.2%; P < 0.001), higher organ failure (45.3% vs 22%; P = 0.001), and prolonged hospitalization (mean, 25.2 [range, 10-63] vs 16 [range, 5-48] days; P < 0.001). CONCLUSIONS: Type 2 diabetes mellitus-related AP is more moderate-to-severe pancreatitis, and it correlates with MRI characteristics of the pancreas itself, hemorrhage, abdominal wall, and infected collections.

MiR-92a promotes stem cell-like properties by activating Wnt/ß-catenin signaling in colorectal cancer.

We previously reported the oncogenic function of miR-92a in colorectal cancer. This study identified that miR-92a was upregulated in chemoresistant colorectal cancer cells and tissues. Ectopic expression of miR-92a conferred resistance to 5-fluorouracil-induced apoptosis in vitro, while antagomiR-92a significantly enhanced chemosensitivity in vivo. Moreover, Overexpression of miR-92a promoted the tumor sphere formation and the expression of stem cell markers. MiR-92a overexpression also displayed higher tumourigenesis in vivo. Furthermore, we demonstrated that miR-92a upregulates the Wnt/ß-catenin signaling activity via directly targeting KLF4, GSK3ß and DKK3, which are multiple level negative regulators of the Wnt/ß-catenin signaling cascade. In addition, our results indicate IL-6/STAT3 pathway increases miR-92a expression by directly targeting its promoter, resulting in Wnt/ß-catenin signaling activation and consequent promotion of stem-like phenotypes of colorectal cancer cells. Our present results suggest the essential role of IL-6/STAT3/miR-92a/Wnt/ß-catenin pathway in regulating the stem cell-like traits of colorectal cancer cells and provide a potential target for colorectal cancer therapy.

Synthesis of a novel adamantyl nitroxide derivative with potent anti-hepatoma activity in vitro and in vivo.

In this study, a novel adamantyl nitroxide derivative was synthesized and its antitumor activities in vitro and in vivo were investigated. The adamantyl nitroxide derivative 4 displayed a potent anticancer activity against all the tested human hepatoma cells, especially with IC50 of 68.1 µM in Bel-7404 cells, compared to the positive control 5-FU (IC50=607.7 µM). The significant inhibition of cell growth was also observed in xenograft mouse model, with low toxicity. Compound 4 suppressed the cell migration and invasion, induced the G2/M phase arrest. Further mechanistic studies revealed that compound 4 induced cell death, which was accompanied with damaging mitochondria, increasing the generation of intracellular reactive oxygen species, cleavages of caspase-9 and caspase-3, as well as activations of Bax and Bcl-2. These results confirmed that adamantyl nitroxide derivative exhibited selective antitumor activities via mitochondrial apoptosis pathway in Bel-7404 cells, and would be a potential anticancer agent for liver cancer.

Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer.

Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.

HuR: a promising therapeutic target for angiogenesis.

Multiple angiogenic factors and inhibitors are becoming potential therapeutic targets for ischemia diseases and cancer. Posttranscriptional regulation through the untranslated region of mRNA is emerging as a critical regulating level in nearly all the biological processes. As a kind of RNA binding proteins, HuR plays important role in augmenting the hypoxic or inflammatory signal, stabilizing the resultant angiogenic factors and promoting the proliferation and migration of endothelial cells. These implicate HuR in the proangiogenic factors mediated angiogenesis in the hypoxia and inflammatory. We consider hypotheses that a more effective angiogenesis can be acquired through strengthened and prolonged effects of angiogenic factors, and that progresses in therapeutic angiogensis might also shed light on the implication of HuR in blocking tumor angiogensis. These considerations may help us to explain HuR as a promising therapeutic target for angiogenesis related disease. It may be a candidate in hypoxia therapy and cancer management.

Role of NLRP3 and NLRP1 inflammasomes signaling pathways in pathogenesis of rheumatoid arthritis.

OBJECTIVES: To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis (RA). METHODS: A total of 36 patients with RA were selected, peripheral blood mononuclear cell (PBMC) and granulocyte were separated from venous blood. RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patients with RA, and detect the mRNA expression of downstream factor IL-1α. The correlation between RA and the expression of NLRP3 and NLRP1 was analyzed. Normal 30 cases were set as control group. RESULTS: Expression levels of NLRP1, and caspase-1 mRNA in PBMC of RA group were significantly lower than those of control group (P<0.05), while there was no significant difference in expression levels of NLRP3, ASC, IL-1α mRNA between these two groups (P>0.05); NLRP3, caspase-1, and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group (P<0.05). There was no correlation between rheumatoid factor and expression levels of NLRP3, ASC, caspase-1 mRNA in RA group (P>0.05); NLRP1, IL-1α mRNA expression level had a negative correlation with anti-rheumatoid factor antibody (P=0.033 2, 0.034 0). CONCLUSIONS: NLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors, and play an important role in RA inflammatory mechanisms.

Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells.

To investigate the influence of hyperglycemia on the severity of choroidal neovascularization (CNV) in diabetic mice, especially the involvement of bone marrow-derived cells (BMCs) and underlying molecular mechanisms. The mice were randomly divided into control group, diabetes group and diabetes treated with insulin group, which were laser treated to induce CNV. The CNV severity was evaluated by fundus fluorescein angiography, HE staining and choroidal flatmount. The BMCs recruitment and differentiation in CNV were examined in GFP chimeric mice by choroidal flatmount and immunofluorescence. The bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and migration were tested in vivo and in vitro. VEGF and SDF-1 production in vivo and in vitro were tested by realtime PCR and ELISA. The CNV severity and expression of VEGF and SDF-1 were enhanced in DM mice compared with control mice and that insulin treatment decreased CNV severity in DM mice. The DM mice demonstrated more BMCs and bone marrow-derived mesenchymal stem cells (BMSCs) recruited and incorporated into CNV, increased ratio of BMCs expressing endothelial cell marker or macrophage marker, and up-regulated expression of VEGF and SDF-1 in CNV. Human BMSCs migration and expression of VEGF and SDF-1 in retinal pigment epithelial (RPE) cells increased when cultured under high glucose. This study suggested that hyperglycemia enhanced the expression of VEGF and SDF-1 in RPE cells, and promoted recruitment and incorporation of BMCs and affected differentiation of BMCs in CNV, which led to more severe CNV in diabetic mice.