Value of Doppler Ultrasonography in Assessing the Efficacy of Diabetic Retinopathy: A Retrospective Analysis.

Objective: To investigate the value of Doppler ultrasound in evaluating the efficacy of diabetic retinopathy. Methods: A retrospective analysis was conducted on 90 hospitalized patients with type 2 diabetes from January 2019 to January 2020. The patients were divided into two groups: 34 cases without retinopathy and 56 cases with diabetic retinopathy. Clinical data and Doppler ultrasonography results were collected and analyzed to evaluate the value of Doppler ultrasound. Results: After treatment, various indicators, including blood glucose, HbA1c, FPG, 2hFPG, HOMA-IR, and FINS, showed significant improvement in both groups (P < .05). There was no significant difference before and after treatment (P > .05). Before treatment, the retinopathy group exhibited significantly different central artery parameters: PSA (8.35 ± 1.08), EDV (5.80±0.62), RI (1.53 ± 0.25), compared to patients without retinopathy: PSA (13.61 ± 1.80), EDV (7.23 ± 0.51), RI (0.85 ± 0.02) (t = 12.019, 11.631, 11.461, P = .01, .01, .00), respectively. After treatment, the central artery parameters improved in both groups. The retinopathy group showed PSA (10.44 ± 0.26), EDV (6.84 ± 0.85), RI (1.01 ± 0.04), while patients without retinopathy exhibited PSA (15.13 ± 1.20), EDV (8.50 ± 0.80), RI (0.71 ± 0.08) (t = 15.94, 12.01, 13.32, P = .01, .01, .01), respectively. Similarly, before treatment, the retinopathy group had different central artery parameters: PSA (30.35 ± 5.15), EDV (8.85 ± 1.67), RI (1.53 ± 0.25), compared to patients without retinopathy: PSA (34.41 ± 5.20), EDV (11.34 ± 2.56), RI (0.88 ± 0.15) (t = 12.108, 11.542, 11.57, P = .01, .01, .01), respectively. After treatment, the central artery parameters improved in both groups. The retinopathy group showed PSA (33.26 ± 4.27), EDV (9.37 ± 1.86), RI (0.98 ± 0.35), while patients without retinopathy exhibited PSA (36.15 ± 4.24), EDV (13.51 ± 2.13), RI (0.76 ± 0.23) (t = 13.84, 12.14, 10.11, P = .01, .01, .01), respectively. Conclusions: Color Doppler ultrasound monitoring of fundus hemodynamic parameters can accurately reflect the changes in blood vessels in diabetic eyes. It provides real-time and objective evaluation of fundus hemodynamic indexes. This technology demonstrates high repeatability and simple operation, making it valuable for the non-invasive detection of early retinopathy.

Hydrogen Attenuates Thyroid Hormone-Induced Cardiac Hypertrophy in Rats by regulating angiotensin II type 1 receptor and NADPH oxidase 2 mediated oxidative stress.

Cardiac hypertrophy occurs as a result of high levels of thyroid hormone, which may contribute to heart failure and is closely related to oxidative stress. Hydrogen is a good antioxidant. In this study, we found that intragastric levothyroxine administration for two weeks caused obvious cardiac hypertrophy without reduced systolic function. Additionally, hydrogen inhalation ameliorated the levothyroxine-induced metabolic increase and cardiac hypertrophy in rats. Serum brain natriuretic peptide expression was also attenuated by hydrogen treatment. However, hydrogen had no significant effect on levothyroxine -induced serum troponin I and serum thyroid hormone changes. Hydrogen treatment also reduced the levothyroxine-induced increase in cardiac malondialdehyde, 8-hydroxy-2-deoxyguanosine and serum hydrogen peroxide levels and upregulated superoxide dismutase and glutathione peroxidase activity. Additionally, western blotting results showed that hydrogen inhalation inhibited the expression of cardiac nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), angiotensin II type 1 receptor, sarcoplasmic reticulum Ca2+-ATPase (SERCA2), phospho-phospholamban and α-myosin heavy chain proteins. In conclusion, the present study revealed a protective effect of hydrogen on levothyroxine -induced cardiac hypertrophy by regulating angiotensin II type 1 receptors and NOX2-mediated oxidative stress in rats.

Hydrogen Attenuates Myocardial Injury in Rats by Regulating Oxidative Stress and NLRP3 Inflammasome Mediated Pyroptosis.

Purpose: Hydrogen (H2) is an antioxidant with anti-inflammatory and apoptosis functions.This study aimed to estimate the effects of H2 on acute myocardial infarction (AMI) in rats and its association with the inhibition of oxidative stress and cardiomyocyte pyroptosis. Methods: Sixty-four rats were randomly divided into three groups (Sham, AMI, and H2). The left anterior descending coronary artery (LAD) of rats in the AMI and H2 groups was ligated, while rats in the Sham group were threaded without ligation. In addition, 2% H2 was administered by inhalation for 24 h after ligation in the H2 group. Transthoracic echocardiography was performed after H2 inhalation, followed by collection of the serum and cardiac tissue of all rats. Results: H2 inhalation ameliorated the cardiac dysfunction, infarct size and inflammatory cell infiltration caused by AMI. Meanwhile, H2 inhalation reduced the concentration of serum Troponin I (TnI), brain natriuretic peptide (BNP), reactive oxygen species (ROS), cardiac malondialdehyde (MDA), and 8-OHdG. In addition, H2 inhalation inhibited cardiac inflammation and pyroptosis relative proteins expression. Conclusion: H2 effectively promoted heart functions in AMI rats by regulating oxidative stress and pyroptosis.

DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma.

Growing evidence suggests that cisplatin and other chemotherapeutic agents promote tumor metastasis while inhibiting tumor growth, which is a critical issue for certain patients in clinical practices. However, the role of chemotherapeutics in promoting tumor metastasis and the molecular mechanism involved are unclear. Here, we investigated the roles of cisplatin in promoting tumor metastasis in lung adenocarcinoma (LUAD). We demonstrated that cisplatin promoted epithelial-mesenchymal transition (EMT), cell motility, and metastasis in vitro and in vivo. The bioinformatic analysis and molecular biology approaches also indicated that DCBLD2 (Discoidin, CUB and LCCL domain containing 2) is a key gene that mediates cisplatin-induced metastasis. DCBLD2 stabilizes ß-catenin by phosphorylating GSK3ß and transporting accumulated ß-catenin to the nucleus to promote the expression of EMT-related transcriptional factors (TFs), ultimately resulting in tumor metastasis. We also identified that cisplatin enhanced DCBLD2 expression by phosphorylating ERK and hence the AP-1-driven transcription of DCBLD2. Furthermore, DCBLD2-specific siRNAs encapsulated by nanocarriers prominently inhibit cisplatin-induced metastasis in vivo. Therefore, DCBLD2 plays a key role in cisplatin-induced metastasis in LUAD and is a potential target for preventing chemotherapy-induced metastasis in vivo.

Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway.

Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients' tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient's survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer.

Association between periostin and epithelial-mesenchymal transition in esophageal squamous cell carcinoma and its clinical significance.

The present study aimed to investigate the association between periostin (POSTN), epithelial cadherin (E-cad) and vimentin (Vim) expression levels in esophageal squamous cell carcinoma (ESCC) tissues, and its clinicopathological significance. A total of 58 patients with esophageal cancer were enrolled. Immunohistochemistry was performed to quantify the expression levels of POSTN, E-cad and Vim. E-cad expression was reduced in ESCC tissue, which was associated with severe tumor node metastasis (TNM) stage (P<0.001), lymphatic metastasis (P<0.001) and vascular invasion (P=0.026). Conversely, Vim expression was found to be increased in ESCC tissues, and had associations with TNM stage (P=0.039) and lymphatic metastasis (P=0.039). POSTN overexpression observed in ESCC cells was associated with attenuation of E-cad expression (P<0.001) and elevated expression levels of Vim (P<0.001). Additionally, significant correlations between the overexpression of POSTN in ESCC cells and clinicopathological variables including TNM staging (P=0.009), degree of differentiation (P<0.001), lymphatic metastasis (P=0.009) and vascular invasion (P=0.002) were verified. Multivariate analysis revealed that overexpression of POSTN in ESCC cancer cells is able to predict the poor prognosis of patients independently of overall survival (P=0.022) and disease free survival (P=0.019). The preliminary findings of the present study demonstrate that POSTN is involved in the epithelial-mesenchymal transition of ESCC cells, and may therefore be a predictive factor for tumor invasion and metastasis, as well as an indicator of poor prognosis for patients with ESCC.

Coexpression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance.

BACKGROUND: Both periostin (PN) and epidermal growth factor receptor (EGFR) can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC) still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. PATIENTS AND METHODS: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ (2) or Kruskal-Wallis method. Spearman's rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan-Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS) and overall survival (OS). RESULTS: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044), differentiation grade (P=0.003), venous invasion (P=0.010), invasion depth (P=0.007), lymphatic metastasis (P=0.000), and tumor stage (P=0.000). The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000), invasion depth (P=0.022), and tumor stage (P=0.000). Kaplan-Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000) and DFS (P=0.000), which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS in the ESCC patients (P<0.05). Moreover, the risk of death for the ESCC patients with low expression of two biomarkers and high expression of single biomarker was 0.243 times (P=0.000) and 0.503 times (P=0.030), respectively, than that for patients with high expression of two biomarkers. CONCLUSION: PN and EGFR are related to miscellaneous clinicopathologic characteristics. Coexpression of PN and EGFR is more closely to be of predictive value on ESCC development and progression, which may offer a novel and potential target strategy for ESCC treatment in the future.

Theoretical investigations on the mechanism of dual 1,3-dipolar cycloaddition of CO2 with isocyanides and alkynes.

The mechanism of dual 1,3-dipolar cycloaddition reaction of CO2 with isocyanides and alkynes was studied using DFT calculations. The calculations show that this three-component reaction takes place from the nucleophilic attack of isocyanides to alkynes with the generation of 1,3-dipolar active species, which requires the largest energy barrier (24.3 kcal mol(-1)) and can be regarded as the rate-determining step for the entire reaction. From 1,3-dipolar species, the desired spiro compound is obtained through the energy-favorable dual 1,3-dipolar cycloaddition channel, including successive asynchronous concerted cycloaddition of CO2 with the 1,3-dipole and cycloaddition of 1,3-dipole with the resultant lactone. Additionally, the competing nucleophilic addition of 1,3-dipole with alkynes could lead to the production of 1,5-dipolar intermediate, which will alternatively react with isocyanides or CO2 and generate several byproducts. The investigations on the substituent effect of both substrates indicate that the substituents on alkynes play the more significant roles in controlling the rate and selectivity of the reaction than those on isocyanides. The moderate electron-withdrawing and conjugate groups on alkynes not only favor the generation of the 1,3-dipole, but also stabilize the negative charge on these species without losing reactivity.

Theoretical study on the mechanism and stereochemistry of the cinchona-thiourea organocatalytic hydrophosphonylation of an α-ketoester.

The mechanism and stereochemistry of the hydrophosphonylation of an α-ketoester with dimethylphosphonate (DMHP) catalyzed by a thiourea-cinchona organocatalyst have been studied by the ONIOM method. The calculations show that the catalytic cycle is a three-step process, including the deprotonation of DMHP, C-P bond formation via nucleophilic addition and proton transfer with the regeneration of the catalyst. The deprotonation of DMHP mediated by the basicity of the quinuclidine nitrogen atom is the rate-determining step for the entire reaction. The activation of the α-ketoester by the thiourea or protonated cinchona moiety of the bifunctional catalyst is comparatively investigated, and the former is energy-preferred. AIM combined with NBO analysis indicate that the multiple hydrogen bonds play essential roles in activating substrates, facilitating charge transfer and stabilizing transition states and intermediates. The stereochemistry of the reaction is controlled by the C-P bond formation step and originated from the chiral induction of the multiple hydrogen-bonding interactions. The bulkier substituent groups on the chiral scaffold of the catalyst may increase rigidity of the catalyst and the asymmetric induction to the substrates. The calculations predict that alkyl substituted α-ketoesters might also be converted to chiral α-hydroxyl phosphonates with high enantioselectivity.