Risk factors for pterygium: Latest research progress on major pathogenesis.

A pterygium is a wedge-shaped fibrovascular growth of the conjunctiva membrane that extends onto the cornea, which is the outer layer of the eye. It is also known as surfer's eye. Growth of a pterygium can also occur on the either side of the eye, attaching firmly to the sclera. Pterygia are one of the world's most common ocular diseases. However, the pathogenesis remains unsolved to date. As the pathogenesis of pterygium is closely related to finding the ideal treatment, a clear understanding of the pathogenesis will lead to better treatment and lower the recurrence rate, which is notably high and more difficult to treat than a primary pterygium. Massive studies have recently been conducted to determine the exact causes and mechanism of pterygia. We evaluated the pathogenetic factors ultraviolet radiation, viral infection, tumor suppressor genes p53, growth factors, oxidative stress, apoptosis and neuropeptides in the progression of the disease. The heightened expression of TRPV1 suggests its potential contribution in the occurrence of pterygium, promoting its inflammation and modulating sensory responses in ocular tissues. Subsequently, the developmental mechanism of pterygium, along with its correlation with dry eye disease is proposed to facilitate the identification of pathogenetic factors for pterygia, contributing to the advancement of understanding in this area and may lead to improved surgical outcomes.

Identification of crosstalk genes relating to ECM-receptor interaction genes in MASH and DN using bioinformatics and machine learning.

This study aimed to identify genes shared by metabolic dysfunction-associated fatty liver disease (MASH) and diabetic nephropathy (DN) and the effect of extracellular matrix (ECM) receptor interaction genes on them. Datasets with MASH and DN were downloaded from the Gene Expression Omnibus (GEO) database. Pearson's coefficients assessed the correlation between ECM-receptor interaction genes and cross talk genes. The coexpression network of co-expression pairs (CP) genes was integrated with its protein-protein interaction (PPI) network, and machine learning was employed to identify essential disease-representing genes. Finally, immuno-penetration analysis was performed on the MASH and DN gene datasets using the CIBERSORT algorithm to evaluate the plausibility of these genes in diseases. We found 19 key CP genes. Fos proto-oncogene (FOS), belonging to the IL-17 signalling pathway, showed greater centrality PPI network; Hyaluronan Mediated Motility Receptor (HMMR), belonging to ECM-receptor interaction genes, showed most critical in the co-expression network map of 19 CP genes; Forkhead Box C1 (FOXC1), like FOS, showed a high ability to predict disease in XGBoost analysis. Further immune infiltration showed a clear positive correlation between FOS/FOXC1 and mast cells that secrete IL-17 during inflammation. Combining the results of previous studies, we suggest a FOS/FOXC1/HMMR regulatory axis in MASH and DN may be associated with mast cells in the acting IL-17 signalling pathway. Extracellular HMMR may regulate the IL-17 pathway represented by FOS through the Mitogen-Activated Protein Kinase 1 (ERK) or PI3K-Akt-mTOR pathway. HMMR may serve as a signalling carrier between MASH and DN and could be targeted for therapeutic development.

Effect of chronic cold stress on gut microbial diversity, intestinal inflammation and pyroptosis in mice.

Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4 °C) for 3 h per day for 3 weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1ß (IL-1ß), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity. Furthermore, persistent cold exposure resulted in the cleavage of pyroptosis-related Gasdermin D (GSDMD) protein by regulating the NLRP3/ASC/caspase-1 and caspase-11 pathway, and activation of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which are strongly associated with changes in gut microbiota diversity. Taken together, these investigations provide new insights into the increased risk of intestinal disorders at extremely low temperatures and establish a theoretical foundation for the advancement of novel pharmaceutical interventions targeting cold-related ailments.

Screening immune-related blood biomarkers for DKD-related HCC using machine learning.

Background: Diabetes mellitus is a significant health problem worldwide, often leading to diabetic kidney disease (DKD), which may also influence the occurrence of hepatocellular carcinoma (HCC). However, the relationship and diagnostic biomarkers between DKD and HCC are unclear. Methods: Using public database data, we screened DKD secretory RNAs and HCC essential genes by limma and WGCNA. Potential mechanisms, drugs, and biomarkers for DKD-associated HCC were identified using PPI, functional enrichment, cMAP, and machine learning algorithms, and a diagnostic nomogram was constructed. Then, ROC, calibration, and decision curves were used to evaluate the diagnostic performance of the nomograms. In addition, immune cell infiltration in HCC was explored using CIBERSORT. Finally, the detectability of critical genes in blood was verified by qPCR. Results: 104 DEGs associated with HCC using WGCNA were identified. 101 DEGs from DKD were predicated on secreting into the bloodstream with Exorbase datasets. PPI analysis identified three critical modules considered causative genes for DKD-associated HCC, primarily involved in inflammation and immune regulation. Using lasso and RM, four hub genes associated with DKD-associated HCC were identified, and a diagnostic nomogram confirmed by DCA curves was established. The results of immune cell infiltration showed immune dysregulation in HCC, which was associated with the expression of four essential genes. PLVAP was validated by qPCR as a possible blood-based diagnostic marker for DKD-related HCC. Conclusion: We revealed the inflammatory immune pathways of DKD-related HCC and developed a diagnostic nomogram for HCC based on PLVAP, C7, COL15A1, and MS4A6A. We confirmed with qPCR that PLVAP can be used as a blood marker to assess the risk of HCC in DKD patients.

The Ameliorative Role of Lico A on Aflatoxin B1-Triggered Hepatotoxicity Partially by Activating Nrf2 Signal Pathway.

Aflatoxin B1 (AFB1) is one of the most harmful and toxic mycotoxins in foods and feeds, posing a serious health risk to both humans and animals, especially its hepatotoxicity. Nuclear factor-erythroid 2-related factor 2 (Nrf2), an important nuclear transcription factor, is generally recognized as a potential target for phytochemicals to ameliorate liver injury. The current study sought to elucidate the molecular processes by which licochalcone A (Lico A), a compound derived from Xinjiang licorice Glycyrrhiza inflate, protects against AFB1 toxicity. In vivo, male wild-type (WT) and Nrf2 knockout (Nrf2-/-) C57BL/6 mice were orally administered AFB1 at 1.5 mg/kg body weight (BW) with or without Lico A at 5 mg/kg. In vitro, AML12 cells were utilized to evaluate the protective effect and mechanism of Lico A against the AFB1-induced hepatotoxicity. Our findings demonstrated that AFB1 caused severe hepatotoxicity, while Lico A treatment successfully relieved the toxicity. Meanwhile, Lico A effectively improved liver injury, inflammatory mediators, oxidative insults, apoptosis, liver fibrosis, and pyroptosis, which contributed to the inhibition of toll receptor 4 (TLR4)-NF-κB/MAPK and NOD-like receptors protein 3 (NLRP3)/caspase-1/GSDMD signaling pathway activation. Furthermore, Lico A was able to enhance the Nrf2 antioxidant signaling pathway. Intriguingly, Lico A still had a protective effect on AFB1-caused liver injury in mice via the inhibition of inflammation and pyroptosis, while apoptosis and liver fibrosis were blocked in the absence of Nrf2. To sum up, the present study first elucidated that Lico A ameliorated AFB1-induced hepatotoxic effects and its main mechanism involved the inhibitory effects on oxidative stress, apoptosis, liver fibrosis, inflammation, and pyroptosis, which might be partially dependent on the regulation of Nrf2. The work may enrich the role and mechanism of Lico A's resistance to liver injury caused by various factors, and its application is promising.

BMP4 inhibits corneal neovascularization by interfering with tip cells in angiogenesis.

Corneal neovascularization (CNV) can lead to impaired corneal transparency, resulting in vision loss or blindness. The primary pathological mechanism underlying CNV is an imbalance between pro-angiogenic and anti-angiogenic factors, with inflammation playing a crucial role. Notably, a vascular endothelial growth factor（VEGF）-A gradient triggers the selection of single endothelial cells（ECs） into primary tip cells that guide sprouting, while a dynamic balance between tip and stalk cells maintains a specific ratio to promote CNV. Despite the central importance of tip-stalk cell selection and shuffling, the underlying mechanisms remain poorly understood. In this study, we examined the effects of bone morphogenetic protein 4 (BMP4) on VEGF-A-induced lumen formation in human umbilical vein endothelial cells (HUVECs) and CD34-stained tip cell formation. In vivo, BMP4 inhibited CNV caused by corneal sutures. This process was achieved by BMP4 decreasing the protein expression of VEGF-A and VEGFR2 in corneal tissue after corneal suture injury. By observing the ultrastructure of the cornea, BMP4 inhibited the sprouting of tip cells and brought forward the appearance of intussusception. Meanwhile, BMP4 attenuated the inflammatory response by inhibiting neutrophil extracellular traps （NETs）formation through the NADPH oxidase-2（NOX-2）pathway. Our results indicate that BMP4 inhibits the formation of tip cells by reducing the generation of NETs, disrupting the dynamic balance of tip and stalk cells and thereby inhibiting CNV, suggesting that BMP4 may be a potential therapeutic target for CNV.

Molecular mechanism of VE-cadherin in regulating endothelial cell behaviour during angiogenesis.

Vascular endothelial (VE)-cadherin, an endothelium-specific adhesion protein, is found in the junctions between endothelial cells (ECs). It's crucial to maintain the homogeneity of ECs. Keeping and controlling the contact between ECs is essential. In addition to its adhesive function, VE-cadherin plays important roles in vascular development, permeability, and tumour angiogenesis. Signal transfer, cytoskeletal reconstruction, and contractile integrating, which are crucial for constructing and maintaining monolayer integrity as well as for repair and regeneration, are the foundation of endothelial cell (EC) junctional dynamics. The molecular basis of adhesion junctions (AJs), which are closely related and work with actin filaments, is provided by the VE-cadherin-catenin complex. They can activate intracellular signals that drive ECs to react or communicate structural changes to junctions. An increasing number of molecules, including the vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial protein tyrosine phosphatase (VE-PTP), have been connected to VE-cadherin in addition to the conventional VE-cadherin-catenin complex. This review demonstrates significant progress in our understanding of the molecular mechanisms that affect VE-cadherin's function in the regulation of EC behaviour during angiogenesis. The knowledge of the molecular processes that control VE-cadherin's role in the regulation of EC behaviour during angiogenesis has recently advanced, as shown in this review.

Advances in cell transplantation therapy for limbal stem cell deficiency.

BACKGROUND: Limbal stem cells (LSCs) are essential for maintaining corneal transparency and ocular surface integrity. Many external factors or genetic diseases can lead to corneal limbal stem cell deficiency (LSCD), resulting in the loss of barrier and corneal epithelial cell renewal functions. Stem cell transplantation is one of the primary treatments for LSCD, including limbal transplantation and cultivated limbal epithelial transplantation. In addition, a variety of non-limbal stem cell lines have been experimented with for LSCD treatment. Biological scaffolds are also used to support in vitro stem cell culture and transplantation. Here, we review the mechanisms of corneal maintenance by LSCs, the clinical stage and surgical treatment of LSCD, the source of stem cells, and the biological scaffolds required for in vitro culture. METHODS: This study is a narrative retrospective study aimed at collecting available information on various aspects of surgical treatments for LSCD. Relevant literature was searched in a range of online databases, including Web of Science, Scopus, and PubMed from 2005 to March, 2023. RESULTS: A total of 397 relevant articles were found, and 49 articles with strong relevance to the studies in this paper were obtained and analyzed. Moreover, 11 of these articles were on the concept of LSCD and the mechanism of LESCs maintaining the corneal epithelium, 3 articles on the staging and grading of LSCD, 17 articles on cell transplantation methods and donor cell sources, and 18 articles on scaffolds for delivering stem cells. We also summarized the advantages and disadvantages of different cell transplantation methods and the benefits and limitations of scaffolds based on the above literature. CONCLUSION: The treatment of LSCD is determined by the clinical stage and whether it involves monocular or binocular eyes. Appropriate surgical techniques should be taken for LSCD patients in order to reconstruct the ocular surface, relieve symptoms, and restore visual function. Meanwhile, biological scaffolds assist in the ex vivo culture and implantation of stem cells.

Progress of corneal morphological examination combined with biomechanical examination in preoperative screening for keratorefractive surgery.

Although corneal refractive surgery has been proven to be excellent in terms of safety and effectiveness, the reduction of postoperative corneal ectasia remains one of the most concerned topics for surgeons. Forme fruste keratoconus (FFKC) is the most important factor that leads to postoperative corneal ectasia, and common preoperative screenings of the condition include corneal morphology examination and corneal biomechanical examination. However, there are limitations to the single morphological examination or biomechanical examination, and the advantages of the combination of the two have been gradually emerging. The combined examination is more accurate in the diagnosis of FFKC and can provide a basis for determining suspected keratoconus. It allows one to measure the true intraocular pressure (IOP) before and after surgery and is recommended for older patients and those with allergic conjunctivitis. This article aims to discuss the application, advantages, and disadvantages of single examination and combined examination in the preoperative screening of refractive surgery, so as to provide a certain reference value for choosing suitable patients for surgery, improving surgical safety, and reducing the risk of postoperative ectasia.

Impact of chronic cold exposure on lung inflammation, pyroptosis and oxidative stress in mice.

Chronic cold exposure, which is the main inducer of lung diseases in high latitudes, affects production efficiency and restricts the development of aquaculture. Although the relationship between cold exposure and susceptibility to the lungs is widely accepted, but the influence between them has not been fully explored. The aim of this study is to understand the underlying mechanism. In the present study, the mice, which are used to establish cold stress (CS)-induced lung injury model, are exposed to cold temperature (4 °C) for 3 h each day for 4 weeks. The results indicate that the expression of heat shock protein 70 (HSP70) is augmented by cold exposure. In addition, chronic cold exposure aggravate the formation of malondialdehyde (MDA) and lead to a significant decrease in the contents of micrococcus catalase (CAT) and glutathione (GSH). Moreover, chronic cold exposure significantly exacerbates the expression of inflammation- and apoptosis-related proteins. The activation of Bax and caspase-3 are significantly augmented. However, that of Bcl-2 is decreased. These results are different from those in room team. The results show that chronic cold exposure plays an important roles in the activation of multiple signaling pathways, such as pyroptosis-related, inflammation-related and oxidative stress-regulated signaling pathways. In summary, these investigations support that chronic cold exposure increase the risk of lung injury by activating inflammation, oxidative stress and pyroptosis.

The research progress on the molecular mechanism of corneal cross-linking in keratoconus treatment.

Keratoconus (KC) is a corneal anomaly that is manifested in a limited cone-like bulge with corneal thinning. Many molecules in the cornea change during the development of KC, including various components of the extracellular matrix, cytokines, cell connection, and cell adhesion-related proteins. Several treatment options are available, with corneal cross-linking (CXL) being the treatment of choice for early KC. However, postoperative complications have been reported in some CXL patients, mainly caused by corneal epithelial resection. Despite the fact that some novel approaches have helped to reduce some of the initial post-operative issues, their effectiveness seems to be inferior to that of the original CXL. To keep effectiveness while avoiding these negative effects, it is necessary to study the mechanism of CXL in KC treatment at the molecular level. This article provides a review of the molecular mechanism of CXL in the treatment of KC from four aspects: enzyme activity, signal transduction pathway, corneal-related proteins, and other KC-related molecules, further confirming the feasibility of CXL treatment of KC, providing new ideas for improving CXL.

Arisaema heterophyllum Blume Monomer Stigmasterol Targets PPARγ and Inhibits the Viability and Tumorigenicity of Lung Adenocarcinoma Cells NCI-H1975.

To clarify the regulatory effect and molecular mechanism of Arisaema heterophyllum Blume (AhBl) monomer stigmasterol on lung adenocarcinoma in human lung adenocarcinoma cells NCI-H1975 cultured in vitro and in nude mice. Oil red O staining, free fatty acid detection, adenosine triphosphate (ATP), and NADPH were applied to elucidate the regulatory effect of stigmasterol on the energy metabolism of NCI-H1975 cells. Simultaneously, colony formation assay and nude mouse tumorigenesis were performed to clarify the underlying mechanisms of stigmasterol on the proliferation and tumorigenesis of NCI-H1975 cells. Furthermore, peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 was supplemented to determine the expression changes of cyclins to clarify the regulation mechanism of stigmasterol. The results revealed that stigmasterol administration markedly inhibited the viability but promoted lipid deposition of NCI-H1975 cells. Meanwhile, the reduction of cell energy metabolism affected cell proliferation and colony formation. qPCR and western blot assays indicated that stigmasterol played a role in regulating the expression of cyclins and PPARγ signaling pathway proteins. Nude mouse tumorigenesis suggested that tumor size and weight in the stigmasterol-treated group were apparently lower as compared with the control group. Tumor tissue cells developed varying degrees of degeneration and large areas of ischemic necrosis presented in the central and peripheral cells. Immunohistochemistry results revealed that Ki67 expression in the stigmasterol group was substantially inhibited, while PPARγ expression was greatly elevated as compared with the control. GW9662 could mediate the inhibitory effect of stigmasterol on NCI-H1975 cells. The current study demonstrated that stigmasterol targeted PPARγ and inhibited the viability and tumorigenicity of lung adenocarcinoma cells NCI-H1975.

Volatile Organic Compounds of Streptomyces sp. TOR3209 Stimulated Tobacco Growth by Up-Regulating the Expression of Genes Related to Plant Growth and Development.

To investigate the mechanism underlying the plant growth-promoting (PGP) effects of strain Streptomyces sp. TOR3209, PGP traits responsible for indoleacetic acid production, siderophore production, and phosphate solubilization were tested by culturing the strain TOR3209 in the corresponding media. The effects of volatile organic compounds (VOCs) produced by the strain TOR3209 on plant growth were observed by co-culturing this strain with tobacco seedlings in I-plates. Meanwhile, the effects of VOCs on tobacco gene expression were estimated by performing a transcriptome analysis, and VOCs were identified by the solid-phase micro-extraction (SPME) method. The results showed positive reactions for the three tested PGP traits in the culture of strain TOR3209, while the tobacco seedlings co-cultured with strain TOR3209 revealed an increase in the fresh weight by up to 100% when compared to that of the control plants, demonstrating that the production VOCs was also a PGP trait. In transcriptome analysis, plants co-cultured with strain TOR3209 presented the highest up-regulated expression of the genes involved in plant growth and development processes, implying that the bacterial VOCs played a role as a regulator of plant gene expression. Among the VOCs produced by the strain TOR3209, two antifungal molecules, 2,4-bis(1,1-dimethylethyl)-phenol and hexanedioic acid dibutyl ester, were found as the main compounds. Conclusively, up-regulation in the expression of growth- and development-related genes via VOCs production is an important PGP mechanism in strain TOR3209. Further efforts to explore the effective VOCs and investigate the effects of the two main VOCs in the future are recommended.

Research Progress on Morphological Changes and Surgery-Related Parameters of Corneal Cap in Small-Incision Lenticule Extraction.

Small-incision lenticule extraction (SMILE) is an "all-in-one" surgical method for refractive correction. An advantage of the SMILE over traditional surgery is that it depends on the corneal cap's design. This review discusses the morphological evaluation of the corneal cap, selection of the corneal cap with different thicknesses and diameters, influence of the corneal cap design on re-treatment, and management of corneal cap-related complications. The following points should be recognized to define the correct morphology and design of the operation-related parameters of the corneal cap during SMILE: (1) the thickness and diameter of the corneal cap are predictable and influence postoperative visual quality, (2) the change in the anterior surface curvature of the corneal cap should be considered in the design of the nomogram value, (3) for patients with moderate myopic correction, early visual quality is better with a 6.9-mm than with a 7.5-mm-diameter corneal cap, (4) there is no significant difference in visual quality or biomechanics among corneal caps with different thicknesses, (5) the primary corneal cap thickness plays an important role in the SMILE re-treatment, (6) a 7.78-mm diameter corneal cap has a greater risk of suction loss than a 7.60-mm diameter corneal cap, (7) if suction loss occurs when lenticular scanning exceeds 10%, then SMILE can be continued by changing the corneal cap thickness, (8) preventive collagen cross-linking with SMILE caps are 90-120 µm thick and 7-7.8 mm in diameter, and (9) properly treating SMILE-related complications ensures better postoperative results. The data presented herein shall deepen the understanding of the importance of the corneal cap during SMILE and provide diversified analysis for personalized operational design of corneal cap parameters.

Progress in understanding of the stalk and tip cells formation involvement in angiogenesis mechanisms.

Vascular sprouting is a key process of angiogenesis and mainly related to the formation of stalk and tip cells. Many studies have found that angiogenesis has a great clinical significance in promoting the functional repair of impaired tissues and anti-angiogenesis is a key to treatment of many tumors. Therefore, how the pathways regulate angiogenesis by regulating the formation of stalk and tip cells is an urgent problem for researchers. This review mainly summarizes the research progress of pathways affecting the formation of stalk and tip cells during angiogenesis in recent years, including the main signaling pathways (such as VEGF-VEGFR-Dll4-Notch signaling pathway, ALK-Smad signaling pathway,CCN1-YAP/YAZ signaling pathway and other signaling pathways) and cellular actions (such as cellular metabolisms, intercellular tension and other actions), aiming to further give the readers an insight into the mechanism of regulating the formation of stalk and tip cells during angiogenesis and provide more targets for anti-angiogenic drugs.

Effects of bone morphogenetic proteins on epithelial repair.

Epithelial tissue has important functions such as protection, secretion, and sensation. Epithelial damage is involved in various pathological processes. Bone morphogenetic proteins (BMPs) are a class of growth factors with multiple functions. They play important roles in epithelial cells, including in differentiation, proliferation, and migration during the repair of the epithelium. This article reviews the functions and mechanisms of the most profoundly studied BMPs in the process of epithelial damage repair and their clinical significance.

The best optical zone for small-incision lenticule extraction in high myopic patients.

Small-incision lenticule extraction (SMILE) is an effective and safe procedure for the correction of myopia due to minimally invasive and noncorneal flap surgery. However, the SMILE procedure has certain requirements for corneal cap thickness, attempted refractive correction, residual stromal bed thickness, and optical zone diameter, which sometimes make surgeons hesitant to choose SMILE or other refractive surgeries. The requirements limit its use in patients with high myopia. The purpose of this review was to find the optimal parameters of SMILE through discussing the best optical zone for high myopic patients, the visual quality of different optical zones, the choice of corneal cap thickness, and their effects on corneal biomechanical parameters, so surgeons can provide reference recommendations for patients with high myopia in choosing a reasonable and safe procedure.

Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions.

Our study aimed to evaluate the protective role and mechanisms of bone marrow mesenchymal stem cells (BMSCs) in hypoxic photoreceptors and experimental retinal detachment. The cellular morphology, viability, apoptosis and autophagy of hypoxic 661w cells and cells cocultured with BMSCs were analysed. In retinal detachment model, BMSCs were intraocularly transplanted, and then, the retinal morphology, outer nuclear layer (ONL) thickness and rhodopsin expression were studied as well as apoptosis and autophagy of the retinal cells. The hypoxia-induced apoptosis of 661w cells obviously increased together with autophagy levels increasing and peaking at 8 hours after hypoxia. Upon coculturing with BMSCs, hypoxic 661w cells had a better morphology and fewer apoptosis. After autophagy was inhibited, the apoptotic 661w cells under the hypoxia increased, and the cell viability was reduced, even in the presence of transplanted BMSCs. In retina-detached eyes transplanted with BMSCs, the retinal ONL thickness was closer to that of the normal retina. After transplantation, apoptosis decreased significantly and retinal autophagy was activated in the BMSC-treated retinas. Increased autophagy in the early stage could facilitate the survival of 661w cells under hypoxic stress. Coculturing with BMSCs protects 661w cells from hypoxic damage, possibly due to autophagy activation. In retinal detachment models, BMSC transplantation can significantly reduce photoreceptor cell death and preserve retinal structure. The capacity of BMSCs to reduce retinal cell apoptosis and to initiate autophagy shortly after transplantation may facilitate the survival of retinal cells in the low-oxygen and nutrition-restricted milieu after retinal detachment.

Regulation of bone morphogenetic protein 4 on epithelial tissue.

Epithelial tissues provide tissue barriers and specialize in organs and glands. When epithelial homeostasis is physiologically or pathologically stimulated, epithelial cells produce mesenchymal cells through the epithelial-mesenchymal transition, forming new tissues, promoting the cure of diseases or leading to illness. A variety of cytokines are involved in the regulation of epithelial cell differentiation. Bone morphogenetic proteins (BMPs), especially the bone morphogenetic protein 4 (BMP4) has a variety of biological functions and plays a prominent role in the regulation of epithelial cell differentiation. BMP4 is an important regulatory factor of a series of life activities in vertebrates, which is also related to cell proliferation, differentiation and mobility, it also has relation with tumor development. This paper mainly reviews the mechanism of BMP4's regulation on epithelial tissues, as well as its effect on the growth, differentiation, benign lesions and malignant lesions of epithelial tissues, and expounds the function of BMP4 in epithelial tissues, to provide theoretical support for the research on reducing epithelial diseases.

Regulation of matrix metalloproteinases 2 and 9 in corneal neovascularization.

Corneal neovascularization (CNV), a pathological process of angiogenesis, can lead to serious consequences in the cornea. CNV is generally proved to associate with inflammation in the cornea closely, which is mainly elicited by the disruption of equilibrium between angiogenic and antiangiogenic factors. Angiogenic factors including vascular endothelial growth factors (VEGFs), basic fibroblast growth factors (bFGFs), and matrix metalloproteinases (MMPs) are vital factors in the formation of CNV. Especially VEGFs are convinced to be the core angiogenic factors in CNV, and MMPs are proved to exert dual effects on the process. Strikingly, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) are determined to play key roles in the formation of CNV, while the mechanism is still vague. In this review, the latest researches are reviewed to discuss the role of MMP-2 and MMP-9 in CNV, respectively, and some inhibitors of them are presented. We hope to provide a new direction of drug research for CNV.