Evaluation of optical coherence tomography angiography metrics in children and adolescents with type 1 diabetes: 4-year longitudinal study.

PURPOSE: To evaluate longitudinal changes in optical coherence tomography angiography (OCTA) metrics in children and adolescents with type 1 diabetes (T1D). METHODS: This prospective observational cohort study included thirty-two eyes from thirty T1D children with no history of diabetic retinopathy (DR) who were followed up for 4 years. Participants underwent OCTA examinations at baseline and during follow-up. Quantitative OCTA metrics were measured using a customized MATLAB algorithm. Generalized mixed-effect models were used to determine their relationship with DR development. Systemic parameters and OCTA metrics were screened using least absolute shrinkage and selection operator to identify predictors for visual function. RESULTS: Over the 4-year period, seven of the included eyes developed DR, and most OCTA metrics decreased with diabetes duration. Higher peripapillary and parafoveal nasal quadrant vessel area density (VAD) in the superficial capillary plexus (SCP) and vessel skeleton density (VSD) in both the SCP and the deep capillary plexus (DCP) were associated with a lower risk of DR in T1D. Parafoveal DCP VSD and VAD in the temporal and inferior quadrants were anticorrelated with changes in best corrected visual acuity. CONCLUSIONS: OCTA metrics dynamically change over the duration of diabetes and can be used as biomarkers to improve the risk evaluation of DR development and visual function in T1D children and adolescents.

YTHDF2-Mediated m6A methylation inhibition by miR27a as a protective mechanism against hormonal osteonecrosis in BMSCs.

BACKGROUND: With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited. OBJECTIVE: We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs. METHODS: We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed. RESULTS: miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH. CONCLUSION: miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.

Comparative genomic analysis reveals expansion of the DnaJ gene family in Lagerstroemia indica and its members response to salt stress.

DnaJs/Hsp40s/JPDs are obligate co-chaperones of heat shock proteins (Hsp70), performing crucial biological functions within organisms. A comparative genome analysis of four genomes (Vitis vinifera, Eucalyptus grandis, Lagerstroemia indica, and Punica granatum) revealed that the DnaJ gene family in L. indica has undergone expansion, although not to the extent observed in P. granatum. Inter-genome collinearity analysis of four plants indicates that members belonging to Class A and B are more conserved during evolution. In L. indica, the expanded members primarily belong to Class-C. Tissue expression patterns and the biochemical characterization of LiDnaJs further suggested that DnaJs may be involved in numerous biological processes in L. indica. Transcriptome and qPCR analyses of salt stressed leaves identified at least ten LiDnaJs that responded to salt stress. In summary, we have elucidated the expansion mechanism of the LiDnaJs, which is attributed to a recent whole-genome triplication. This research laid the foundation for functional analysis of LiDnaJs and provides gene resources for breeding salt-tolerant varieties of L. indica.

Erratum: Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol: Erratum.

[This corrects the article DOI: 10.7150/ijbs.20316.].

Three-Year Follow-Up Study Investigating Changes in Retinal Vascular Morphology and the Relationship with Diabetic Retinopathy in Children with Type 1 Diabetes Mellitus.

INTRODUCTION: This study aimed to investigate changes in retinal microvascular morphology and associated factors, and their relationship with diabetic retinopathy (DR) in children with type 1 diabetes mellitus (T1DM). METHODS: Thirty-eight children enrolled in this 3-year follow-up study underwent complete ophthalmic examinations including fundus photography. Retinal vascular parameters were measured automatically and compared between baseline and follow-up. Multiple linear regression was used to investigate factors affecting changes in vascular parameters. Binary logistic regression was used to analyze the relationship between retinal microvascular morphology and DR. RESULTS: The caliber of all retinal vessels (within 1-1.5 papillary diameter [PD] from the center of the optic disc, p = 0.030; 1.5-2 PD, p = 0.003), arterioles, and venules (1.5-2 PD, p = 0.001) was narrower in nearly all regions in the follow-up group compared with the baseline group. Vascular tortuosity increased in the central part of the retina and decreased in the periphery. The density (1-1.5 PD, p = 0.030) and fractal dimension (p = 0.037) of retinal vessels were increased at the end of the follow-up compared with baseline. Retinal vascular caliber was independently correlated with DR (odds ratio 0.793 [95% confidence interval 0.633-0.993]; p = 0.044). CONCLUSION: Retinal microvascular morphology in children with T1DM varied with the disease course. Narrower retinal vessels may be an independent risk factor for DR. Results of this study emphasized the importance of regular follow-up of fundus vascular morphology for the detection of early DR in children with T1DM.

Baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating ATP-sensitive potassium channels.

Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.

Salvianolic acid A alleviates heart failure with preserved ejection fraction via regulating TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways.

Heart failure with preserved ejection fraction (HFpEF) is a morbid, fatal, and common syndrome for which lack of evidence-based therapies. Salvianolic acid A (SAA), a major active ingredient of Salvia miltiorrhiza Burge, has shown potential to protect against cardiovascular diseases. This study aims to elucidate whether SAA possessed therapeutic activity against HFpEF and explore the potential mechanism. HFpEF mouse model was established infusing a combination of high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) for 14 weeks. After 10 weeks of feeding, HFpEF mice were given SAA (2.5, 5, 10 mg/kg) via oral gavage for four weeks. Body weight, blood pressure, blood lipids, glucose tolerance, exercise performance, cardiac systolic/diastolic function, cardiac pathophysiological changes, and inflammatory factors were assessed. Experimental results showed that SAA reduced HFpEF risk factors, such as body weight gain, glucose intolerance, lipid disorders, and increased exercise tolerance in HFpEF mice. Moreover, SAA not only relieved myocardial hypertrophy and fibrosis by reducing interventricular septal wall thickness, left ventricular posterior wall thickness, left ventricular mass, heart index, cardiomyocyte cross-sectional area and cardiac collagen content, but also improved cardiac diastolic function via reducing E/E' ratio. Finally, SAA inhibited TLR2/TLR4-mediated Myd88 activation and its downstream molecules TRAF6 and IRAK4, which decreases the release of proinflammatory cytokines and mediators through NF-κB and p38 MAPK pathways. In conclusion, SAA could attenuate cardiac inflammation and cardiac disfunction by TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways in HFpEF mice, which provides evidence for SAA as a potential drug for treatment of HFpEF in clinic.

Puerarin Inhibits NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis via P2X7 Receptor in Cardiomyocytes and Macrophages.

Diabetic cardiomyopathy (DCM) is a critical complication of long-term chronic diabetes mellitus, and it is characterized by myocardial fibrosis and myocardial hypertrophy. Previous studies have shown that the pyroptosis pathway was significantly activated in DCM and may be related to the P2X7 receptor. However, the role of the P2X7 receptor in the development of DCM with pyroptosis is still unclear. In this study, we aimed to explore the mechanism of puerarin and whether the P2X7 receptor can be used as a new target for puerarin in the treatment of DCM. We adopted systematic pharmacology and bioinformatic approaches to identify the potential targets of puerarin for treating DCM. Additionally, we employed D-glucose-induced H9C2 rat cardiomyocytes and lipopolysaccharide-treated RAW264.7 mouse mononuclear macrophages as the in vitro model on DCM research, which is close to the pathological conditions. The mRNA expression of cytokines in H9C2 cells and RAW264.7 macrophages was detected. The protein expressions of NLRP3, N-GSDMD, cleaved-caspase-1, and the P2X7 receptor were investigated with Western blot analysis. Furthermore, molecular docking of puerarin and the P2X7 receptor was conducted based on CDOCKER. A total of 348 puerarin targets and 4556 diabetic cardiomyopathy targets were detected, of which 218 were cross targets. We demonstrated that puerarin is effective in enhancing cardiomyocyte viability and improving mitochondrial function. In addition, puerarin is efficacious in blocking NLRP3-Caspase-1-GSDMD-mediated pyroptosis in H9C2 cells and RAW264.7 cells, alleviating cellular inflammation. On the other hand, similar experimental results were obtained by intervention with the P2X7 receptor antagonist A740003, suggesting that the protective effects of puerarin are related to the P2X7 receptor. The molecular docking results indicated key binding activity between the P2X7 receptor and puerarin. These findings indicate that puerarin effectively regulated the pyroptosis signaling pathway during DCM, and this regulation was associated with the P2X7 receptor.

Bacterial lipopolysaccharide related genes signature as potential biomarker for prognosis and immune treatment in gastric cancer.

The composition of microbial microenvironment is an important factor affecting the development of tumor diseases. However, due to the limitations of current technological levels, we are still unable to fully study and elucidate the depth and breadth of the impact of microorganisms on tumors, especially whether microorganisms have an impact on cancer. Therefore, the purpose of this study is to conduct in-depth research on the role and mechanism of prostate microbiome in gastric cancer (GC) based on the related genes of bacterial lipopolysaccharide (LPS) by using bioinformatics methods. Through comparison in the Toxin Genomics Database (CTD), we can find and screen out the bacterial LPS related genes. In the study, Venn plots and lasso analysis were used to obtain differentially expressed LPS related hub genes (LRHG). Afterwards, in order to establish a prognostic risk score model and column chart in LRHG features, we used univariate and multivariate Cox regression analysis for modeling and composition. In addition, we also conducted in-depth research on the clinical role of immunotherapy with TMB, MSI, KRAS mutants, and TIDE scores. We screened 9 LRHGs in the database. We constructed a prognostic risk score and column chart based on LRHG, indicating that low risk scores have a protective effect on patients. We particularly found that low risk scores are beneficial for immunotherapy through TIDE score evaluation. Based on LPS related hub genes, we established a LRHG signature, which can help predict immunotherapy and prognosis for GC patients. Bacterial lipopolysaccharide related genes can also be biomarkers to predict progression free survival in GC patients.

Insights into Endothelin Receptors in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease which affects the cardiopulmonary system; it is defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as measured by right heart catheterization at rest, and is caused by complex and diverse mechanisms. In response to stimuli such as hypoxia and ischemia, the expression and synthesis of endothelin (ET) increase, leading to the activation of various signaling pathways downstream of it and producing effects such as the induction of abnormal vascular proliferation during the development of the disease. This paper reviews the regulation of endothelin receptors and their pathways in normal physiological processes and disease processes, and describes the mechanistic roles of ET receptor antagonists that are currently approved and used in clinical studies. Current clinical researches on ET are focused on the development of multi-target combinations and novel delivery methods to improve efficacy and patient compliance while reducing side effects. In this review, future research directions and trends of ET targets are described, including monotherapy and precision medicine.

Salvianolic acid A improve mitochondrial respiration and cardiac function via inhibiting apoptosis pathway through CRYAB in diabetic cardiomyopathy.

Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.

Deciphering the Mechanism of Wogonin, a Natural Flavonoid, on the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Integrating Network Pharmacology and In Vitro Validation.

Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against PH through network pharmacology and further verify it through biological experiments in pulmonary arterial smooth muscle cells (PASMCs). The potential targets and pathways of wogonin against PH were predicted and analyzed by network pharmacology methods and molecular docking technology. Subsequently, the proliferation of PASMCs was induced by platelet-derived growth factor-BB (PDGF-BB). Cell viability and migration ability were examined. The method of Western blot was adopted to analyze the changes in related signaling pathways. Forty potential targets related to the effect of wogonin against PH were obtained. Based on the protein-protein interaction (PPI) network, gene-ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment, and molecular docking, it was shown that the effect of wogonin against PH is closely related to the proliferation of PASMCs and the hypoxia-inducible factor-1α (HIF-1α) pathway. A variety of results from biological experiments verified that wogonin can effectively inhibit the proliferation, migration, and phenotypic transformation of PDGF-BB-mediated PASMCs. In addition, the anti-proliferation effect of wogonin may be achieved by regulating HIF-1/ NADPH oxidase 4 (NOX4) pathway.

Network pharmacology approach and experimental verification of Dan-Shen Decoction in the treatment of ischemic heart disease.

CONTEXT: Dan-Shen Decoction, which is composed of Danshen, Tanxiang and Sharen, has a good therapeutic effect on ischemic heart disease (IHD). However, systematic research on the exact mechanism of action of Dan-Shen Decoction is still lacking. The anti-IHD effect of Dan-Shen Decoction was examined in this study using a systematic pharmacological method. OBJECTIVE: This study validates the efficacy and explores the potential mechanisms of Dan-Shen Decoction in treating IHD by integrating network pharmacology analyses and experimental verification. MATERIALS AND METHODS: The active components, critical targets and potential mechanisms of Dan-Shen Decoction against IHD were predicted by network pharmacology and molecule docking. H9c2 cells were pretreated with various 1 µg/mL Dan-Shen Decoction for 2 h before induction with 1000 µmol/L CoCl2 for 24 h. The cell viability was detected by CCK8, and protein expression was detected by western blots. RESULTS: The network pharmacology approach successfully identified 69 active components in Dan-Shen Decoction, and 122 potential targets involved in the treatment of IHD. The in vitro experiments indicate that the anti-IHD effect of Dan-Shen Decoction may be closely associated with targets such as AKT1 and MAPK1, as well as biological processes such as cell proliferation, inflammatory response, and metabolism. CONCLUSIONS: This study not only provides new insights into the mechanism of Dan-Shen Decoction against IHD, but also provides important information and new research ideas for the discovery of anti-IHD compounds from traditional Chinese medicine.

Ultrafast Early Warning of Heart Attacks through Plasmon-Enhanced Raman Spectroscopy using Collapsible Nanofingers and Machine Learning.

As the leading cause of death, heart attacks result in millions of deaths annually, with no end in sight. Early intervention is the only strategy for rescuing lives threatened by heart disease. However, the detection time of the fastest heart-attack detection system is >15 min, which is too long considering the rapid passage of life. In this study, a machine learning (ML)-driven system with a simple process, low-cost, short detection time (only 10 s), and high precision is developed. By utilizing a functionalized nanofinger structure, even a trace amount of biomarker leaked before a heart attack can be captured. Additionally, enhanced Raman profiles are constructed for predictive analytics. Five ML models are developed to harness the useful characteristics of each Raman spectrum and provide early warnings of heart attacks with >98% accuracy. Through the strategic combination of nanofingers and ML algorithms, the proposed warning system accurately provides alerts on silent heart-attack attempts seconds ahead of actual attacks.

The potential effect of BMSCs with miR-27a in improving steroid-induced osteonecrosis of the femoral head.

Steroid induced osteonecrosis of the femoral head (ONFH) frequently leads to femoral head collapse and subsequent hip arthritis. This study aimed to investigate the potential therapeutic mechanism of miR-27a on steroid-induced ONFH. Levels of IL-6, TNF-α, miR-27a, Runx2, PPAR-γ and ApoA5 were first examined in bone marrow tissues from steroid-induced ONFH and controls. Subsequently, we overexpressed or knocked down miR-27a in bone marrow mesenchymal stem cells (BMSCs) and detected cell proliferation, osteogenic differentiation, adipogenic differentiation. In addition, miR-27a mimics and BMSCs were injected into the established steroid-induced ONFH rats, and the osteoprotective effects of both were evaluated. Dual luciferase reporter was used to test the targeting effect of miR-27a-3p and PPARG. miR-27a and Runx2 were lowly expressed in steroid-induced ONFH, PPAR-γ and ApoA5 were highly expressed. Overexpression of miR-27a in BMSCs promoted cell proliferation and osteogenic differentiation, inhibited adipogenic differentiation. Furthermore, increasing miR-27a and BMSCs obviously reduced bone loss in steroid induced ONFH rats. The expressions of Runx2 in BMSCs and steroid-induced ONFH rats was significantly up-regulated, while IL-6, TNF-α, PPAR-γ and ApoA5 were down-regulated with miR-27a overexpression. Additionally, PPARG was the target of miR-27a-3p. The results of the present study reveal a role for miR-27a in promoting osteogenesis and may have a synergistic effect with BMSCs.

Puerarin-V Improve Mitochondrial Respiration and Cardiac Function in a Rat Model of Diabetic Cardiomyopathy via Inhibiting Pyroptosis Pathway through P2X7 Receptors.

There is a new form of puerarin, puerarin-V, that has recently been developed, and it is unclear whether puerarin-V has a cardioprotective effect on diabetic cardiomyopathy (DCM). Here, we determined whether puerarin-V had any beneficial influence on the pathophysiology of DCM and explored its possible mechanisms. By injecting 30 mg/kg of STZ intraperitoneally, diabetes was induced in rats. After a week of stability, the rats were injected subcutaneously with ISO (5 mg/kg). We randomly assigned the rats to eight groups: (1) control; (2) model; (3) metformin; (4-6) puerarin-V at different doses; (7) puerarin (API); (8) puerarin injection. DCM rats were found to have severe cardiac insufficiency (arrythmia, decreased LVdP/dt, and increased E/A ratio). In addition, cardiac injury biomarkers (cTn-T, NT-proBNP, AST, LDH, and CK-MB), inflammatory cytokines (IL-1ß, IL-18, IL-6, and TNF-α), and oxidative damage markers (MDA, SOD and GSH) were markedly increased. Treatment with puerarin-V positively adjusts these parameters mentioned above by improving cardiac function and mitochondrial respiration, suppressing myocardial inflammation, and maintaining the structural integrity of the cardiac muscle. Moreover, treatment with puerarin-V inhibits the P2X7 receptor-mediated pyroptosis pathway that was upregulated in diabetic hearts. Given these results, the current study lends credence to the idea that puerarin-V can reduce myocardial damage in DCM rats. Furthermore, it was found that the effect of puerarin-V in diabetic cardiomyopathy is better than the API, the puerarin injection, and metformin. Collectively, our research provides a new therapeutic option for the treatment of DCM in clinic.

A Generic Pixel Pitch Calibration Method for Fundus Camera via Automated ROI Extraction.

Pixel pitch calibration is an essential step to make the fundus structures in the fundus image quantitatively measurable, which is important for the diagnosis and treatment of many diseases, e.g., diabetes, arteriosclerosis, hereditary optic atrophy, etc. The conventional calibration approaches require the specific parameters of the fundus camera or several specially shot images of the chess board, but these are generally not accessible, and the calibration results cannot be generalized to other cameras. Based on automated ROI (region of interest) and optic disc detection, the diameter ratio of ROI and optic disc (ROI-disc ratio) is quantitatively analyzed for a large number of fundus images. With the prior knowledge of the average diameter of an optic disc in fundus, the pixel pitch can be statistically estimated from a large number of fundus images captured by a specific camera without the availability of chess board images or detailed specifics of the fundus camera. Furthermore, for fundus cameras of FOV (fixed field-of-view), the pixel pitch of a fundus image of 45° FOV can be directly estimated according to the automatically measured diameter of ROI in the pixel. The average ROI-disc ratio is approximately constant, i.e., 6.404 ± 0.619 in the pixel, according to 40,600 fundus images, captured by different cameras, of 45° FOV. In consequence, the pixel pitch of a fundus image of 45° FOV can be directly estimated according to the automatically measured diameter of ROI in the pixel, and results show the pixel pitches of Canon CR2, Topcon NW400, Zeiss Visucam 200, and Newvision RetiCam 3100 cameras are 6.825 ± 0.666 µm, 6.625 ± 0.647 µm, 5.793 ± 0.565 µm, and 5.884 ± 0.574 µm, respectively. Compared with the manually measured pixel pitches, based on the method of ISO 10940:2009, i.e., 6.897 µm, 6.807 µm, 5.693 µm, and 6.050 µm, respectively, the bias of the proposed method is less than 5%. Since our method doesn't require chess board images or detailed specifics, the fundus structures on the fundus image can be measured accurately, according to the pixel pitch obtained by this method, without knowing the type and parameters of the camera.

Effects of air pollution on myopia: an update on clinical evidence and biological mechanisms.

Myopia is one of the most common forms of refractive eye disease and considered as a worldwide pandemic experienced by half of the global population by 2050. During the past several decades, myopia has become a leading cause of visual impairment, whereas several factors are believed to be associated with its occurrence and development. In terms of environmental factors, air pollution has gained more attention in recent years, as exposure to ambient air pollution seems to increase peripheral hyperopia defocus, affect the dopamine pathways, and cause retinal ischemia. In this review, we highlight epidemiological evidence and potential biological mechanisms that may link exposure to air pollutants to myopia. A thorough understanding of these mechanisms is a key for establishing and implementing targeting strategies. Regulatory efforts to control air pollution through effective policies and limit individual exposure to preventable risks are required in reducing this global public health burden.

Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure.

Heart failure (HF) is a clinical syndrome of cardiac insufficiency caused by abnormalities in cardiac structure and function that arise for various reasons, and it is the final stage of most cardiovascular diseases' progression. Total flavonoid extract from Dracocephalum moldavica L. (TFDM) has many pharmacological and biological roles, such as cardioprotective, neuroprotective, anti-atherogenic, antihypertensive, anti-diabetic, anti-inflammatory, antioxidant, etc. However, its effect on HF and its molecular mechanism are still unclear. In this study, we used systems pharmacology and an animal model of HF to investigate the cardioprotective effect of TFDM and its molecular mechanism. Eleven compounds in TFDM were obtained from the literature, and 114 overlapping genes related to TFDM and HF were collected from several databases. A PPI network and C-T network were established, and GO enrichment analysis and KEGG pathway analysis were performed. The top targets from the PPI network and C-T network were validated using molecular docking. The pharmacological activity was investigated in an HFpEF (heart failure with preserved ejection fraction) mouse model. This study shows that TFDM has a protective effect on HFpEF, and its protective mechanism may be related to the regulation of proinflammatory cytokines, apoptosis-related genes, fibrosis-related genes, etc. Collectively, this study offers new insights for researchers to understand the protective effect and mechanism of TFDM against HFpEF using a network pharmacology method and a murine model of HFpEF, which suggest that TFDM is a promising therapy for HFpEF in the clinic.

Mechanistic and therapeutic perspectives of baicalin and baicalein on pulmonary hypertension: A comprehensive review.

Pulmonary hypertension (PH) is a chronic and fatal disease, for which new therapeutic drugs and approaches are needed urgently. Baicalein and baicalin, the active compounds of the traditional Chinese medicine, Scutellaria baicalensis Georgi, exhibit a wide range of pharmacological activities. Numerous studies involving in vitro and in vivo models of PH have revealed that the treatment with baicalin and baicalein may be effective. This review summarizes the potential mechanisms driving the beneficial effects of baicalin and baicalein treatment on PH, including anti-inflammatory response, inhibition of pulmonary smooth muscle cell proliferation and endothelial-to-mesenchymal transformation, stabilization of the extracellular matrix, and mitigation of oxidative stress. The pharmacokinetics of these compounds have also been reviewed. The therapeutic potential of baicalin and baicalein warrants their continued study as natural treatments for PH.