Targeting MicroRNA in myopia: Current insights.

Myopia, the most prevalent eye condition, has sparked notable interest regarding its origin and prevention. MicroRNAs (miRNAs) are short, non-coding RNA strands typically consisting of 18-24 nucleotides. They play a central role in post-transcriptional gene regulation and are closely associated with both normal and pathological processes in organisms. Recent advances in next-generation sequencing and bioinformatics have provided novel insights into miRNA expression and its regulatory role in myopia. This review discusses the distinct expression patterns, regulatory functions, and potential pathways of miRNAs involved in the onset and progression of myopia. The primary objective of this review was to provide valuable insights into molecular mechanisms underlying myopia and the contribution of miRNAs. These insights are expected to pave the way for further exploration of the molecular mechanisms, diagnosis, treatment, and clinical applications of myopia.

Melanin-like nanoparticles alleviate ischemia-reperfusion injury in the kidney by scavenging reactive oxygen species and inhibiting ferroptosis.

Kidney transplantation is essential for patients with end-stage renal disease; however, ischemia-reperfusion injury (IRI) during transplantation can lead to acute kidney damage and compromise survival. Recent studies have reported that antiferroptotic agents may be a potential therapeutic strategy, by reducing production of reactive oxygen species (ROS). Therefore, we constructed rutin-loaded polydopamine nanoparticles (PEG-PDA@rutin NPs, referred to as PPR NPs) to eliminate ROS resulting from IRI. Physicochemical characterization showed that the PPR NPs were ∼100 nm spherical particles with good ROS scavenging ability. Notably, PPR NPs could effectively enter lipopolysaccharide (LPS)-treated renal tubular cells, then polydopamine (PDA) released rutin to eliminate ROS, repair mitochondria, and suppress ferroptosis. Furthermore, in vivo imaging revealed that PPR NPs efficiently accumulated in the kidneys after IRI and effectively protected against IRI damage. In conclusion, PPR NPs demonstrated an excellent ability to eliminate ROS, suppress ferroptosis, and protect kidneys from IRI.

Dopamine Receptor 1 Treatment Promotes Epithelial Repair of Corneal Injury by Inhibiting NOD-Like Receptor Protein 3-Associated Inflammation.

Purpose: To elucidate the influence of dopamine receptor 1 (DRD1) on the proliferation of mouse corneal epithelial cells (MCECs) under inflammatory conditions. Methods: In vitro, immortalized MCECs (iMCECs) were treated with IL-1ß, with and without pcDNA3.1_DRD1. Primary MCECs (pMCECs) were exposed to IL-1ß, with and without DRD1 agonist (A68930). Cell proliferation was quantified using the Cell Counting Kit-8 (CCK-8) assay and immunofluorescence staining for Ki-67 and p63. Expression levels of NOD-like receptor protein 3 (NLRP3), IL-1ß, and IL-6 were assessed. To establish a corneal injury model in mice, a 2-mm superficial keratectomy was performed. Either 0.1% A68930 or PBS was topically administered three times daily to the injured eyes for up to 5 days post-injury. Immunofluorescence analysis was employed to evaluate the expression of Ki-67, p63, and CD45 in mouse corneas. Western blotting and real-time quantitative PCR were utilized for quantitative analysis of DRD1, NLRP3, IL-1ß, and IL-6 in mouse corneas. Corneal epithelial regeneration was monitored through fluorescein sodium staining for a duration of up to 5 days following the injury. Results: Overexpression of DRD1 and A68930 promoted MCEC proliferation and suppressed the expression of NLRP3, IL-1ß, and IL-6 in vitro. Topical application of the 0.1% A68930 following mechanical corneal injury in mice led to increased Ki-67 and p63 expression compared to PBS treatment. Furthermore, topical administration of the 0.1% A68930 reduced the expression of CD45, NLRP3, IL-1ß, and IL-6. Analysis with fluorescein sodium indicated accelerated corneal epithelial regeneration in the 0.1% A68930 treatment group. Conclusions: DRD1 treatment counteracts NLRP3-associated inflammation and facilitates epithelial repair of corneal injury.

Circadian rhythm, ipRGCs, and dopamine signalling in myopia.

Myopia, a common ophthalmic disorder, places a high economic burden on individuals and society. Genetic and environmental factors influence myopia progression; however, the underlying mechanisms remain unelucidated. This paper reviews recent advances in circadian rhythm, intrinsically photosensitive retinal ganglion cells (ipRGCs), and dopamine (DA) signalling in myopia and proposes the hypothesis of a circadian rhythm brain retinal circuit in myopia progression. The search of relevant English articles was conducted in the PubMed databases until June 2023. Based on the search, emerging evidence indicated that circadian rhythm was associated with myopia, including circadian genes Bmal1, Cycle, and Per. In both humans and animals, the ocular morphology and physiology show rhythmic oscillations. Theoretically, such ocular rhythms are regulated locally and indirectly via the suprachiasmatic nucleus, which receives signal from the ipRGCs. Compared with the conventional retinal ganglion cells, ipRGCs can sense the presence of light because of specific expression of melanopsin. Light, together with ipRGCs and DA signalling, plays a crucial role in both circadian rhythm and myopia. In summary, regarding myopia progression, a circadian rhythm brain retinal circuit involving ipRGCs and DA signalling has not been well established. However, based on the relationship between circadian rhythm, ipRGCs, and DA signalling in myopia, we hypothesised a circadian rhythm brain retinal circuit.

Taurine alleviates high-fat-high-glucose-induced pancreatic islet ß-cell oxidative stress and apoptosis in rat.

The effect of taurine (TAU) as a specific regulatory mediator on pancreatic function in obese rats induced by a high-fat-high-glucose (HFHG) diet was investigated. We fed male Sprague-Dawley rats under different conditions, namely the control, HFHG, TAU, and HFHG + TAU treatment groups for 4 months. Compared with the HFHG group, TAU supplementation significantly reduced malondialdehyde levels and increased superoxide dismutase, total antioxidant capacity, and glutathione levels in the rat pancreas. In addition, TAU significantly decreased the level of reactive oxygen species, and markedly increased the activity of heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP-1), and nuclear factor erythrocyte-2-related factor 2 (Nrf2) in the rat pancreas. Notably, HFHG diet could induce pancreatic injury in the rats through the Nrf2/HO-1 signaling pathway and activate the mitochondrial channel-mediated apoptotic signaling pathway. The addition of TAU significantly improved the pancreatic tissue injury induced by the HFHG diet in the rats and reduced the protein expression of Caspase-3, Cleaved-caspase-3, Caspase-9 and Bcl-2 associated protein X (BAX), and increased the protein expression of B-cell lymphoma-2 (Bcl-2). In conclusion, this experiment confirmed that TAU could alleviate the oxidative stress and apoptosis induced by the HFHG diet in rat pancreatic ß-cells.

The role of regulatory T cells in the pathogenesis of acute kidney injury.

The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis.

Taurine Protects against the Fatty Liver Hemorrhagic Syndrome in Laying Hens through the Regulation of Mitochondrial Homeostasis.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease caused by fat deposition in the liver of humans and mammals, while fatty liver hemorrhagic syndrome (FLHS) is a fatty liver disease in laying hens which can increase the mortality and cause severe economic losses to the laying industry. Increasing evidence has shown a close relationship between the occurrence of fatty liver disease and the disruption of mitochondrial homeostasis. Studies have proven that taurine can regulate hepatic fat metabolism, reduce hepatic fatty deposition, inhibit oxidative stress, and alleviate mitochondrial dysfunction. However, the mechanisms by which taurine regulates mitochondrial homeostasis in hepatocytes need to be further studied. In this study, we determined the effects and mechanisms of taurine on high-energy low-protein diet-induced FLHS in laying hens and in cultured hepatocytes in free fatty acid (FFA)-induced steatosis. The liver function, lipid metabolism, antioxidant capacity, mitochondrial function, mitochondrial dynamics, autophagy, and biosynthesis were detected. The results showed impaired liver structure and function, mitochondrial damage and dysfunction, lipid accumulation, and imbalance between mitochondrial fusion and fission, mitochondrial autophagy, and biosynthesis in both FLHS hens and steatosis hepatocytes. Taurine administration can significantly inhibit the occurrence of FLHS, protect mitochondria in hepatocytes from disease induced by lipid accumulation and FFA, up-regulate the expression levels of Mfn1, Mfn2, Opa1, LC3I, LC3II, PINK1, PGC-1α, Nrf1, Nrf2, and Tfam, and down-regulate the expression levels of Fis1, Drp1, and p62. In conclusion, taurine can protect laying hens from FLHS through the regulation of mitochondrial homeostasis, including the regulation of mitochondrial dynamics, autophagy, and biosynthesis.

Experimental Study on the Mechanical Properties and Acoustic Emission Characteristics of Different Bedding High-Rank Coals.

Bedding has an important influence on the macroscopic and microscopic mechanical properties of coal, and the mechanical properties of coal and rock mass and acoustic emission characteristics are very important for rock burst monitoring and warning. In order to explore the influence of different beddings on the mechanical properties and acoustic emission characteristics of high-rank coal, using the RMT-150B electrohydraulic servo rock mechanics test system and the DS5 acoustic emission analyzer, the uniaxial compression and acoustic emission characteristics of high-rank coals with different beddings (parallel bedding 0°, oblique bedding 30, 45, 60°, and vertical bedding 90°) were investigated. The results show that the uniaxial compressive strength and deformation modulus of vertical stratified coal samples are the largest, which are 28.924 MPa and 2.95 GPa, while the average values of uniaxial compressive strength and deformation modulus of oblique stratified coal samples are the smallest, which are 10.91 MPa and 1.776 GPa, respectively. With the increase of the bedding angle, the uniaxial compressive strength of high-rank coal decreases first and then increases. The stress-strain process of coal varies greatly with different high stratification grades (parallel bedding 0°, oblique bedding 30°, 45°, 60° and vertical bedding 90°). The loading times of parallel, oblique, and vertical beddings are 700, 450, 370, 550, and 600 s, and the acoustic emission mutation point values are 495, 449, 350, 300, and 410 s. The mutation point value can be used as precursor information to judge the failure of high-rank coal in different beddings. Research results to find the high-rank coal destruction instability prediction method and the index provide a basis; further damage to the acoustic emission testing high order coal provides reference significance; and the use of acoustic emission in the monitoring and early warning of percussive ground pressure, the bedding surface of coal, and the actual stress on site should be considered.

Improving myopia awareness via school-based myopia prevention health education among Chinese students.

AIM: To investigate the myopia awareness level, knowledge, attitude, and skills at baseline and to implement and evaluate the efficacy of myopia prevention health education among Chinese students. METHODS: A total of 1000 middle school students from 2 middle schools were invited to participate in the study, and myopia prevention health education was conducted. The students were assessed at baseline, followed by a survey. The efficacy of health education was evaluated using the self-comparison method pre- and post-health education. RESULTS: The study included 957 and 850 pre- and post-health education participants, respectively. The baseline knowledge of all respondents on myopic symptoms (87.5%), myopia is a risk of eyes (72.9%), myopia prevention (91.3%), myopia increases with age (86.7%), performing periodic eye examinations (92.8%), and one first, one foot, and one inch (84.8%) significantly increased after health education (P<0.001 for all). However, the percentage of students who still did not think it necessary to take breaks after 30-40min of continuous near work was 27.0%. The opinion that "myopia can be cured" was still present in 38.3%. CONCLUSION: Implementing school-based myopia prevention health education improves knowledge, attitudes, and skills regarding myopia among Chinese middle school students.

Taurine reduces apoptosis mediated by endoplasmic reticulum stress in islet ß-cells induced by high-fat and -glucose diets.

Poor eating habits, especially high-fat and -glucose diets intake, can lead to endoplasmic reticulum (ER) stress in islet ß-cells, insulin resistance, and islet ß-cell dysfunction and cause islet ß-cell apoptosis, which leads to type 2 diabetes mellitus (T2DM). Taurine is a crucial amino acid in the human body. In this study, we aimed to explore the mechanism through which taurine reduces glycolipid toxicity. INS-1 islet ß-cell lines were cultured with a high concentration of fat and glucose. SD rats were fed a high-fat and -glucose diet. MTS, Transmission electron microscopy, Flow cytometry, Hematoxylin-eosin, TUNEL, Western blotting analysis and other methods were used to detect relevant indicators. The research found that taurine increases the cell activity, reduces the apoptosis rate, alleviates the structural changes of ER under high-fat and -glucose exposure models. In addition, taurine improves blood lipid content and islets pathological changes, regulates the relative protein expression in ER stress and apoptosis, increases the insulin sensitivity index (HOMA-IS), and reduces the insulin resistance index (HOMAC-IR) of SD rats fed with a high-fat and -glucose diet.

HES1 deficiency impairs development of human intestinal mesenchyme by suppressing WNT5A expression.

Serious intestinal side-effects that target the NOTCH-HES1 pathway in human cancer differentiation therapy make it necessary to understand the pathway at the human organ level. Herein, we endogenously introduced HES1-/- mutations into human embryonic stem cells (hESCs) and differentiated them into human intestinal organoids (HIO). The HES1-/- hESCs retained ES cell properties and showed gene expression patterns similar to those of wild-type hESCs when they differentiated into definitive endoderm and hindgut. During the formation of the HES1-/- lumen we noted an impaired development of mesenchymal cells in addition to the increased differentiation of secretory epithelium. RNA-Seq revealed that inhibited development of the mesenchymal cells may have been due to a downregulation of WNT5A signaling. Overexpression of HES1 and silencing of WNT5A in the intestinal fibroblast cell line CCD-18Co indicated that HES1 was involved in the activation of WNT5A-induced fibroblast growth and migration, suggesting the likelihood of the Notch pathway in epithelial-mesenchymal crosstalk. Our results facilitated the identification of more precise underlying molecular mechanisms displaying distinct roles in HES1 signaling in stromal and epithelial development in human intestinal mucosa.

Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.

BACKGROUND: Protein kinase C delta (PRKCD) and caspase recruitment domain family member 9 (CARD9) are genes involved in B and T cell activation, and cytokine production, which are vital mechanisms underlying autoimmune disease development. This study aimed to explore the association of the PRKCD and CARD9 genes with Vogt-Koyanagi-Harada disease (VKH) disease. The case-control study was performed to in 912 patients with VKH and 878 normal controls. MassARRAY system, SHEsis online platform, real-time PCR, and enzyme-linked immunosorbent assay were used to detect genotyping, haplotyping, mRNA expression, and cytokine levels, respectively. RESULTS: We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10-5, OR = 1.810; Pc = 2.76 × 10-5, OR = 1.698, respectively). However, the rs74437127 T allele, and rs3812555 TC genotype and T allele were linked with decreased susceptibility to VKH (Pc = 0.020, OR = 0.616; Pc = 7.85 × 10-5, OR = 0.559; Pc = 2.76 × 10-5, OR = 0.589, respectively). PRKCD ATG and CARD9 GCTTA haplotypes decreased susceptibility to VKH (Pc = 3.11 × 10-3, OR = 0.594; Pc = 5.00 × 10-3, OR = 0.639, respectively). Functional studies on rs3812555 genotyped individuals revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production than TC/TT carriers (P = 1.00 × 10-4; P = 2.00 × 10-3, respectively). CONCLUSIONS: We found an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility and revealed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-α.

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

A radiomics-based model can predict recurrence-free survival of hepatocellular carcinoma after curative ablation.

BACKGROUND: Prediction of early recurrence (ER) of HCC after radical treatment is of great significance for follow-up and subsequent treatment, and there is a lot of unmet needs. Here, our goal is to develop and validate a radiomics nomogram that can predict ER after curative ablation. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC through this retrospective analysis. METHODS: 149 HCC patients treated between November 2008 and February 2018 were enrolled and randomly divided into training cohort (n = 105) and validation cohort (n = 44). The survival endpoint was recurrence-free survival (RFS). A total of 16908 radiomics features were extracted from the contrast-enhanced MR images of each patient. The minimum redundancy maximum relevance algorithm (mRMR) and random survival forest (RSF) were used for feature selection. Twelve kinds of support vector machine (SVM) models, a Cox regression model (Cox PH), a random survival forest (RSF) model and a gradient boosting model (GBoost) were used to build a radiomics signature. These models were trained after adjusting the model parameters using 5-fold cross-validation. The best models were selected according to the C-index. RESULTS: Using the machine learning (ML) framework, 40 features were identified that demonstrated good prediction of HCC recurrence across all cohorts. The random survival forest (RSF) model showed higher prognostic value, with a C-index of 0.733-0.801 and an integrated Brier score of 0.147-0.165, compared with other SVM models, Cox regression models, etc. (all P < 0.05). Time-dependent receiver operating characteristic (ROC) curve analysis, survival analysis, and decision curve analysis (DCA) were used to verify the performance of the RSF model in predicting tumor recurrence. CONCLUSION: We successfully built a radiomics-based RSF model with integrated radiomics and clinicopathological features that can potentially be used to predict ER after curative ablation in HCC patients.

Dietary taurine effect on intestinal barrier function, colonic microbiota and metabolites in weanling piglets induced by LPS.

Diarrhea in piglets is one of the most important diseases and a significant cause of death in piglets. Preliminary studies have confirmed that taurine reduces the rate and index of diarrhea in piglets induced by LPS. However, there is still a lack of relevant information on the specific target and mechanism of action of taurine. Therefore, we investigated the effects of taurine on the growth and barrier functions of the intestine, microbiota composition, and metabolite composition of piglets induced by LPS. Eighteen male weaned piglets were randomly divided into the CON group (basal diet + standard saline injection), LPS group (basal diet + LPS-intraperitoneal injection), and TAU + LPS group (basal diet + 0.3% taurine + LPS-intraperitoneal injection). The results show that taurine significantly increased the ADG and decreased the F/G (p < 0.05) compared with the group of CON. The group of TAU + LPS significantly improved colonic villous damage (p < 0.05). The expression of ZO-1, Occludin and Claudin-1 genes and proteins were markedly up-regulated (p < 0.05). Based on 16s rRNA sequencing analysis, the relative abundance of Lactobacilluscae and Firmicutes in the colon was significantly higher in the LPS + TAU group compared to the LPS group (p < 0.05). Four metabolites were significantly higher and one metabolite was significantly lower in the TAU + LPS group compared to the LPS group (p < 0.01). The above results show that LPS disrupts intestinal microorganisms and metabolites in weaned piglets and affects intestinal barrier function. Preventive addition of taurine enhances beneficial microbiota, modulates intestinal metabolites, and strengthens the intestinal mechanical barrier. Therefore, taurine can be used as a feed additive to prevent intestinal damage by regulating intestinal microorganisms and metabolites.

CARARIME: Interactive web server for comprehensive analysis of renal allograft rejection in immune microenvironment.

Background: Renal transplantation is a very effective treatment for renal failure patients following kidney transplant. However, the clinical benefit is restricted by the high incidence of organ rejection. Therefore, there exists a wealth of literature regarding the mechanism of renal transplant rejection, including a large library of expression data. In recent years, research has shown the immune microenvironment to play an important role in renal transplant rejection. Nephrology web analysis tools currently exist to address chronic nephropathy, renal tumors and children's kidneys, but no such tool exists that analyses the impact of immune microenvironment in renal transplantation rejection. Methods: To fill this gap, we have developed a web page analysis tool called Comprehensive Analysis of Renal Allograft Rerejction in Immune Microenvironment (CARARIME). Results: CARARIME analyzes the gene expression and immune microenvironment of published renal transplant rejection cohorts, including differential analysis (gene expression and immune cells), prognosis analysis (logistics regression, Univariable Cox Regression and Kaplan Meier), correlation analysis, enrichment analysis (GSEA and ssGSEA), and ROC analysis. Conclusions: Using this tool, researchers can easily analyze the immune microenvironment in the context of renal transplant rejection by clicking on the available options, helping to further the development of approaches to renal transplant rejection in the immune microenvironment field. CARARIME can be found in http://www.cararime.com.

Experimental Study on the Variation Mechanism of Permeability and Seepage Characteristics of High-Rank Coal with Different Bedding.

In order to understand the variation mechanism of permeability and seepage characteristics of high-rank coal with different bedding, we prepared cylindrical raw coal samples according to the bedding angles of 0, 30, 45, 60, and 90° and conducted permeability tests under two stress paths (stress path 1, unloading confining pressure under constant axial pressure; stress path 2, simultaneous loading axial pressure and unloading confining pressure). The results show that the relationship between the permeability and effective stress of high-rank coal with different bedding in the two stress paths conforms to an exponential function, and the permeability increases gradually with an increase in differential stress. Under the two stress paths, the initial permeability of different bedding under the loading axial pressure and confining pressure shows a pattern of a maximum for parallel bedding coal samples, followed by oblique bedding coal samples, and a minimum for vertical bedding coal samples. Under path 1, the increase in the permeability of the oblique bedding is 21.4 times that of the vertical bedding and 14.94 times that of the parallel bedding, and under path 2, the increase in the permeability of the oblique bedding is 26.45 times that of the vertical bedding and 142.11 times that of the parallel bedding; the coal samples of the oblique bedding suffer the greatest damage. The increase in the permeability of parallel bedding coal samples, oblique bedding coal samples, and vertical bedding coal samples under path 2 is 1.47 times, 13.96 times, and 11.3 times the increase in the permeability of the corresponding coal samples under path 1, respectively, and the damage produced by coal samples under path 2 is greater than that under path 1.

Research progress on exosomes/microRNAs in the treatment of diabetic retinopathy.

Diabetic retinopathy (DR) is the leakage and obstruction of retinal microvessels caused by chronic progressive diabetes that leads to a series of fundus lesions. If not treated or controlled, it will affect vision and even cause blindness. DR is caused by a variety of factors, and its pathogenesis is complex. Pericyte-related diseases are considered to be an important factor for DR in many pathogeneses, which can lead to DR development through direct or indirect mechanisms, but the specific mechanism remains unclear. Exosomes are small vesicles of 40-100 nm. Most cells can produce exosomes. They mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells. In humans, intermittent hypoxia has been reported to alter circulating excretory carriers, increase endothelial cell permeability, and promote dysfunction in vivo. Therefore, we believe that the changes in circulating exocrine secretion caused by hypoxia in DR may be involved in its progress. This article examines the possible roles of miRNAs, proteins, and DNA in DR occurrence and development and discusses their possible mechanisms and therapy. This may help to provide basic proof for the use of exocrine hormones to cure DR.

Association of CDK6 gene polymorphisms with Behcet's disease in a Han Chinese population.

Cyclin-dependent kinases 4/6 (CDK4/6) and D1-type cyclins (CCND1) can regulate the pro-inflammatory functions of various cytokines during the inflammatory response. This study investigated the association between CDK4/6-CCND1 variants and susceptibility in patients with Behcet's disease (BD). This case-control study enrolled 542 patients with BD and 754 healthy controls. Fourteen tagged single nucleotide polymorphisms (tag SNPs) of the CDK4/6-CCND1 gene were genotyped using the Sequenom MassARRAY system and iPLEX® Pro assay. The results indicated that the frequency of the CDK6 rs2282983 TT genotype was higher in the BD group than the control group (Pc = 0.040, OR = 1.408, 95% CI = 1.124-1.765), and CDK6 rs2282983 CT and rs42034 AG were negatively associated with BD (Pc = 3.647 × 10-4, OR = 0.598, 95% CI = 0.471-0.758; Pc = 0.039, OR = 0.626, 95% CI = 0.459-0.852, respectively). Furthermore, statistical analysis showed that CDK6 rs2282983 TT and CT genotypes were significantly associated with skin lesions in patients with BD (Pc = 0.042, OR = 1.436, 95% CI = 1.130-1.824; Pc = 0.001, OR = 0.594, 95% CI = 0.461-0.764, respectively). This study suggests that the CDK6 loci rs2282983 and rs42034 might confer genetic susceptibility to BD in a Han Chinese population, which could provide new insights into the pathogenesis of BD.