Paeoniflorigenone inhibits ovarian cancer metastasis through targeting the MUC1/Wnt/ß­catenin pathway.

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial­mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit­8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S­phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/ß­catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/ß­catenin pathway to induce anti­metastatic, anti­invasive and anti­EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

Application of surface-enhanced Raman spectroscopy to human serum for diagnosing liver cancer.

This study investigates the application of surface-enhanced Raman spectroscopy (SERS) in the diagnosis of liver cancer using Ag@SiO2 nanoparticles as SERS substrates. A SERS test was conducted on serum samples obtained from patients with liver cancer and healthy individuals. After repeated several times experiments, it was found that the best SERS spectrum was obtained when the volume ratio of serum to deionized water was 1:2. Moreover, data preprocessing was performed on the tested SERS spectrum, and the preprocessed spectral data were combined with principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) for further analysis to classify the serum samples of patients with liver cancer and healthy individuals. The results showed that the classification effect of standard normal variate spectral data combined with the OPLS-DA was the best for the serum samples, with a classification accuracy of 97.98%, sensitivity of 97.14%, and specificity of 98.44%. Therefore, the SERS technology can be developed as a favorable method for the accurate diagnosis of liver cancer in the future.

An anti-inflammatory chondroitin sulfate-poly(lactic-co-glycolic acid) composite electrospinning membrane for postoperative abdominal adhesion prevention.

Postoperative abdominal adhesion is a very common and serious complication, resulting in pain, intestinal obstruction and heavy economic burden. Post-injury inflammation that could activate the coagulation cascade and deposition of fibrin is a major cause of adhesion. Many physical barrier membranes are used to prevent abdominal adhesion, but their efficiency is limited due to the lack of anti-inflammatory activity. Here, an electrospinning membrane composed of poly(lactic-co-glycolic acid) (PLGA) providing support and mechanical strength and chondroitin sulfate (CS) conferring anti-inflammation activity is fabricated for preventing abdominal adhesion after injury. The PLGA/CS membrane shows a highly dense fiber network structure with improved hydrophilicity and good cytocompatibility. Importantly, the PLGA/CS membrane with a mass ratio of CS at 20% provides superior anti-adhesion efficiency over a native PLGA membrane and commercial poly(D, L-lactide) (PDLLA) film in abdominal adhesion trauma rat models. The mechanism is that the PLGA/CS membrane could alleviate the local inflammatory response as indicated by the promoted percentage of anti-inflammatory M2-type macrophages and decreased expression of pro-inflammatory factors, such as IL-1ß, TNF-α and IL-6, resulting in the suppression of the coagulation system and the activation of the fibrinolytic system. Furthermore, the deposition of fibrin at the abdominal wall was inhibited, and the damaged abdominal tissue was repaired with the treatment of the PLGA/CS membrane. Collectively, the PLGA/CS electrospinning membrane is a promising drug-/cytokine-free anti-inflammatory barrier for post-surgery abdominal adhesion prevention and a bioactive composite for tissue regeneration.

Posterior scleral birefringence measured by triple-input polarization-sensitive imaging as a biomarker of myopia progression.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

Applications of Genomics and Transcriptomics in Precision Medicine for Myopia Control or Prevention.

Myopia is a globally emerging concern accompanied by multiple medical and socio-economic burdens with no well-established causal treatment to control thus far. The study of the genomics and transcriptomics of myopia treatment is crucial to delineate disease pathways and provide valuable insights for the design of precise and effective therapeutics. A strong understanding of altered biochemical pathways and underlying pathogenesis leading to myopia may facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures. In this review, we summarize current data about the genomics and transcriptomics of myopia in human and animal models. We also discuss the potential applicability of these findings to precision medicine for myopia treatment.

Quantitative determination of carbosulfan residues by surface-enhanced Raman spectroscopy.

Carbosulfan gets easily decomposed into carbofuran and 3-Hydroxy carbofuran in vegetables and forms harmful residues. To detect the residues of carbosulfan in vegetables (for example, cowpeas), a super-sensitive method of surface-enhanced Raman spectroscopy (SERS) was used in this work. Silver sol was prepared as the SERS substrate. To solve the adsorption problem of carbosulfan on Ag nanoparticles, 2, 6-dichloroquinone-4-chlorimide (chromogenic agent), and sodium hydroxide were added in carbosulfan to generate a complex, which was then mixed with the silver sol in the best proportion to examine SERS spectra. According to density functional theory calculations, the spectral peak positions of carbosulfan were determined. The optimal mixing ratio of the complex and the silver sol to obtain the optimal SERS spectrum and the detection limit of carbosulfan were investigated. The ultra-sensitive detection of carbosulfan residues (8.7 × 10-11 g/L) in cowpeas was realized. The results of this work indicate that SERS is a promising technique for detecting single-molecule pesticide residues in vegetables.

A novel small compound TOIDC suppresses lipogenesis via SREBP1-dependent signaling to curb MAFLD.

BACKGROUND: Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD. METHODS: Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo. RESULTS: We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1). CONCLUSIONS: Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD.

Choroidal Thickness in Early Postnatal Guinea Pigs Predicts Subsequent Naturally Occurring and Form-Deprivation Myopia.

Purpose: To identify choroidal characteristics associated with susceptibility to development of naturally occurring and experimentally induced myopia. Methods: We compared choroidal properties between pigmented and albino guinea pig (GP) strains. Biometry, cycloplegic refractive error (RE), and eye wall sublayer thickness were measured from 171 GPs at postnatal day (P)6, 14, and 28. Forty-three P14 GPs underwent two-week monocular form-deprivation myopia (FDM). En face images of choroidal vasculature were obtained with a customized swept-source optical coherence tomography. Multivariate regression analyses were performed, with P28 RE as the outcome and P14 choroidal thickness (ChT) as the main predictor variable. Proteomic analysis was performed on choroidal tissue from P14 albino and pigmented GPs. Results: At P14, RE was correlated with thickness of the choroid (ß = 0.06), sclera (ß = 0.12), and retina (ß = 0.27; all P < 0.001). P14 ChT was correlated with P28 RE both with (ß = 0.06, P = 0.0007) and without FDM (ß = 0.05, P = 0.008). Multivariate regression analysis, taking into account FDM (versus physiological growth) and strain, revealed that for every 10-µm greater ChT at P14, P28 RE was 0.50D more positive (P = 0.005, n = 70). En face images of choroidal sublayers showed that albino choroids were relatively underdeveloped, with frequent avascular regions. Consistent with this finding, proteomic analysis suggested abnormalities of the nitric oxide system in the albino GP choroid. Conclusions: Current results are consistent with the notion that greater ChT could protect from or delay the onset of myopia, while lower ChT is associated with greater susceptibility to myopia development. The underlying mechanism could be related to dysfunction of the choroidal vascular system.

Effect of topical latanoprost on choroidal thickness and vessel area in Guinea pigs.

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p > 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 µm at baseline and 0.04 ± 0.06 µm after 2 weeks of treatment (SD-OCT; p > 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 µm2 after treatment (p = 0.04). While this study was limited to otherwise untreated young adult guinea pigs, the possibility that choroidal vessel enlargement contributes to the previously reported inhibitory effect of topical latanoprost on myopia progression in young guinea pigs warrants investigation.

Copper-Catalyzed Multicomponent Reactions of Intramolecular and Intermolecular Thiotrifluoromethylation of Alkenes: Access to CF3-Containing 2-Iminothiazolidines and Isothioureas.

A copper-catalyzed multicomponent reaction of secondary amines bearing allyl substitution, isothiocyanates, and Togni reagent II has been developed under Cs2CO3 in DCE at 75 °C. An intermolecular multicomponent reaction of thioureas, activated and unactivated alkenes, and Togni reagent II has also been developed under DMAP in acetonitrile at room temperature. These two alkene difunctionalization reactions provide CF3-containing 2-iminothiazolindines and isothioureas in moderate to excellent yields with broad substrate scope and good functional group tolerance, respectively.

Diagnosis of Lung Cancer by FTIR Spectroscopy Combined With Raman Spectroscopy Based on Data Fusion and Wavelet Transform.

Lung cancer is a fatal tumor threatening human health. It is of great significance to explore a diagnostic method with wide application range, high specificity, and high sensitivity for the detection of lung cancer. In this study, data fusion and wavelet transform were used in combination with Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy to study the serum samples of patients with lung cancer and healthy people. The Raman spectra of serum samples can provide more biological information than the FTIR spectra of serum samples. After selecting the optimal wavelet parameters for wavelet threshold denoising (WTD) of spectral data, the partial least squares-discriminant analysis (PLS-DA) model showed 93.41% accuracy, 96.08% specificity, and 90% sensitivity for the fusion data processed by WTD in the prediction set. The results showed that the combination of FTIR spectroscopy and Raman spectroscopy based on data fusion and wavelet transform can effectively diagnose patients with lung cancer, and it is expected to be applied to clinical screening and diagnosis in the future.

Ag-Catalyzed or Ag/PPh3-Catalyzed Chemoselective Switchable Cascade Reactions of N-Propargyl Thiocarbamoyl Fluorides and Malonate Esters.

The divergent chemoselective synthesis of 2-methylene-2,3-dihydrothiazoles and 4-benzylidene pyrrolidine-2-thiones (most with E stereoselectivity) from N-propargyl thiocarbamoyl fluorides and malonate esters in moderate to excellent yields with a broad substrate scope and functional group tolerance has been accomplished. AgNTf2 catalyst at 60 °C in dichloroethane provided 4-benzylidene pyrrolidine-2-thiones. AgOTf catalyst and PPh3 ligand in refluxing acetonitrile resulted in a complete switch in the reactivity of formed α,α-diester thioamide intermediates followed by isomerization to access 2-methylene-2,3-dihydrothiazoles.

Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics.

Although obstructive sleep apnea (OSA) has been clinically reported to be associated with acute coronary syndrome (ACS), the pathogenesis between the two is unclear. Herein, we analyzed and screened out the prospective molecular marker. To explore the candidate genes, as well as signaling cascades involved in ACS related to OSA, we extracted the integrated differentially expressed genes (DEGs) from the intersection of genes from the Gene Expression Omnibus (GEO) cohorts and text mining, followed by enrichment of the matching cell signal cascade through DAVID analysis. Moreover, the MCODE of Cytoscape software was employed to uncover the protein-protein interaction (PPI) network and the matching hub gene. A total of 17 and 56 integrated human DEGs in unstable angina (UA) and myocardial infarction (MI) group associated with OSAs that met the criteria of |log2 fold change (FC)|≥ 1, adjusted P < 0.05, respectively, were uncovered. After PPI network construction, the top five hub genes associated with UA were extracted, including APP, MAPK3, MMP9, CD40 and CD40LG, whereas those associated with MI were PPARG, MAPK1, MMP9, AGT, and TGFB1. The establishment of the aforementioned candidate key genes, as well as the enriched signaling cascades, provides promising molecular marker for OSA-related ACS, which will to provide a certain predictive value for the occurrence of ACS in OSA patients in the future.

Using image data to numerically correct the jitter in polarization depth encoding PS-OCT.

In swept source polarization depth encoding polarization sensitive optical coherence tomography (PS-OCT), the laser jitter induces additional noise to the polarization sensitive measurement. In this Letter, we developed a numerical algorithm to correct the jitter phases based on the image data using the Mueller matrix calculus. The algorithm was demonstrated on in vivo retina imaging of a guinea pig with a custom-built PS-OCT system. The performance of the proposed algorithm was almost comparable to the conventional method of using a physical calibration signal. By not requiring a hardware generated calibration signal and k-clock, the proposed algorithm is useful to reduce the complexity and the cost of a polarization depth encoding PS-OCT system.

Pd-Catalyzed Coupling of Thioamides with N-Tosylhydrazones/Trapping by Esters Cascade Reaction.

N,N-Disubstituted thioamides coupled with N-tosylhydrazones under Pd(TFA)2/tBuXPhos catalyst and NaOtBu, and the intermediates from palladium carbene migratory insertion containing ß-hydrogen were trapped by intramolecular esters activated by BF3·Et2O instead of undergoing ß-H elimination, providing polyfunctional thiophen-3(2H)-ones with sulfur-containing tetrasubstituted carbon centers in moderate to good yields. The reaction features the formation of three bonds in a single operation, odorless, safe, and easily available substrates, wide substrate scope, and excellent functional group tolerance.

Antioxidant activity of selenium-enriched Chrysomyia megacephala (Fabricius) larvae powder and its impact on intestinal microflora in D-galactose induced aging mice.

BACKGROUND: The purpose of this study was to assess the antioxidative activity of selenium-enriched Chrysomyia Megacephala (Fabricius) (C. megacephala) larvae powder (SCML) and its impact on the diversity and structure of intestinal microflora in a mouse model of D-galactose (D-gal)-induced oxidative damage. METHODS: Sixty male ICR mice were equally randomized to a normal control (NC) group, a model group, a positive group, a low-dose SCML (L-SCML) group, a mid-dose SCML (M-SCML) group, and a high-dose SCML (H-SCML) group. Animals in NC and model groups received water, animals in the positive group received 40 mg/Kg vitamin E (VE), and those in the three SCML groups received SCML which include 300, 1000 and 3000 µg/Kg selenium (Se) respectively. An oxidative damage model induced by subcutaneous injection of D-gal for 6 weeks via the neck was established. Serum oxidative stress levels and tissue appearance were evaluated. Tissues oxidative stress levels were detected by commercially available kit. Nuclear erythroid 2-related factor (Nrf2) and gut microbiota were determined by western blot and high throughput sequencing 16S rRNA gene respectively. RESULTS: An oxidative damage model was established successfully as represented by a significant elevation of malondialdehyde (MDA) and protein carbonylation, and inhibition of the antioxidants including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and glutathione (GSH). It was found that oxidative damage and histological alterations were attenuated, the expression of Kelch-like ECH-associated protein (Keap1) was decreased, and the expression of Nrf2 and hemeoxygenase-1 (HO-1) was increased after SCML treatment. In addition, significant changes were observed in the gut microbiota, including Proteobacteria and the ratio of Bacteroidetes to Firmicutes at the phylum level, as well as Helicobacter, Clostridium and Lactobacillus at the genus level. CONCLUSION: SCML exerted an antioxidative effect in vivo, probably by increasing the antioxidant activity and reducing the production of oxidation products via the Nrf2 signaling pathway. SCML could also redress the intestinal flora imbalance induced by oxidative stress. All these findings suggest that SCML could serve as a functional food and natural drug additive to protect the human body against oxidative damage.

Cobalt-Catalyzed Switchable Intramolecular Thioenolization/C-H Thiolation and C(sp2)-H/C(sp3)-H Dehydrogenative Coupling.

Mild cobalt-catalyzed switchable regioselective and chemoselective thioenolization/C-H thiolation and C(sp2)-H/C(sp3)-H dehydrogenative couplings of N-aryl-N-alkyl-thioamides are developed, providing 2-methylene-2,3-dihydrobenzo[d]thiazoles and thio-oxindoles in moderate to excellent yields from the same precursors, respectively. Details mechanistic studies suggest that the thioenolization/C-H thiolation process involves a radical mechanism, whereas the C(sp2)-H/C(sp3)-H dehydrogenative coupling might proceed through an electrophilic cobaltation(III) pathway. Thus, the selectivity for either product is achieved by accessing unique catalytic cycles involving different valence states for cobalt.

Kaempferol Prevents Against Ang II-induced Cardiac Remodeling Through Attenuating Ang II-induced Inflammation and Oxidative Stress.

Heart failure characterized by cardiac remodeling is a global problem. Angiotensin II (Ang II) induces cardiac inflammation and oxidative stress, which also is implicated in the pathophysiology of adverse collagen accumulation-induced remodeling. Kaempferol (KPF), a kind of flavonoid compounds, is capable of anti-inflammatory and antioxidant activities. However, the target of KPF still remains blurred. In this study, we investigated the effect of KPF on Ang II-induced collagen accumulation and explored the underlying mechanisms. Our results suggested that KPF prevented Ang II-induced cardiac fibrosis and dysfunction, in mice challenged with subcutaneous injection of Ang II. In culture cells, KPF significantly reduced Ang II-induced collagen accumulation. Furthermore, KPF remarkably decreased inflammation and oxidative stress in Ang II-stimulated cardiac fibroblasts by modulating NF-κB/mitogen-activated protein kinase and AMPK/Nrf2 pathways.

[Age distribution characteristics of intestinal segmented filamentous bacteria and their relationship with intestinal mucosal immunity in children].

OBJECTIVE: To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity. METHODS: The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry. RESULTS: The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age: the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P<0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P<0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P<0.05). CONCLUSIONS: Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.

Ileal perforation caused by a fish bone shortly after drug-eluting stent implantation for acute myocardial infarction.

During the past century, the incidence of myocardial infarction has markedly increased worldwide. Percutaneous coronary intervention with stent implantation is often considered as the first-choice treatment, especially in emergency cases. Current guidelines recommend delayed elective noncardiac surgery for such vulnerable patients. However, few suggestions are available regarding the exact treatment strategy for patients who have already undergone percutaneous coronary intervention but suddenly need emergent noncardiac surgery for an unrelated reason. We herein present a case involving a patient with acute myocardial infarction who had undergone implantation of a drug-eluting stent and developed an ileal perforation due to fish bone ingestion 3 days postoperatively. After carefully balancing the risks of stent thrombosis and uncontrollable bleeding, dual antiplatelet therapy and low-molecular-weight heparin were given with close monitoring. Emergency laparotomy and partial small bowel resection surgery were then performed, after which the patient eventually recovered. This case indicates a possible management strategy for patients with acute myocardial infarction complicated by emergency noncardiac surgery.