Flavonoid extracted from Epimedium attenuate cGAS-STING-mediated diseases by targeting the formation of functional STING signalosome.

Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow-derived macrophages (BMDMs), THP-1 (Tohoku Hospital Pediatrics-1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS-STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN-ß, CXCL10 and ISG15) and pro-inflammatory cytokines (IL-6 and TNF-α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK-binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS-STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) deficiency, and the non-alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS-STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS-STING signalling pathway.

Pectoral muscle removal in mammogram images: A novel approach for improved accuracy and efficiency.

PURPOSE: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra). METHODS: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast Health Cohort at Washington University School of Medicine. RESULTS: Our proposed algorithm exhibits lower mean error of 12.22% in comparison to Libra's estimated error of 20.44%. This 40% gain in accuracy was statistically significant (p < 0.001). The computational time for the proposed algorithm is 5.4 times faster when compared to Libra (5.1 s for proposed vs. 27.7 s for Libra per mammogram). CONCLUSION: We present a novel approach for pectoral muscle removal in mammogram images that demonstrates significant improvement in accuracy and efficiency compared to existing method. Our findings have important implications for the development of computer-aided systems and other automated tools in this field.

NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis.

OBJECTIVE: Recent studies indicate that N-acetyltransferase 10 (NAT10)-mediated ac4C modification plays unique roles in tumour metastasis and immune infiltration. This study aimed to uncover the role of NAT10-mediated ac4C in fibroblast-like synoviocytes (FLSs) functions and synovial immune cell infiltration in rheumatoid arthritis (RA). METHODS: FLSs were obtained from active established patients with RA. Protein expression was determined by western blotting or immunohistochemistry or multiplexed immunohistochemistry. Cell migration was measured using a Boyden chamber. ac4C-RIP-seq combined with RNA-seq was performed to identify potential targets of NAT10. RNA immunoprecipitation was used to validate the interaction between protein and mRNA. NAT10 haploinsufficiency, inhibitor remodelin or intra-articular Adv-NAT10 was used to suppress arthritis in mice with delayed-type hypersensitivity arthritis (DYHA) and collagen II-induced arthritis (CIA) and rats with CIA. RESULTS: We found elevated levels of NAT10 and ac4C in FLSs and synovium from patients with RA. NAT10 knockdown or specific inhibitor treatment reduced the migration and invasion of RA FLSs. Increased NAT10 level in the synovium was positively correlated with synovial infiltration of multiple types of immune cells. NAT10 inhibition in vivo attenuated the severity of arthritis in mice with CIA and DTHA, and rats with CIA. Mechanistically, we explored that NAT10 regulated RA FLS functions by promoting stability and translation efficiency of N4-acetylated PTX3 mRNA. PTX3 also regulated RA FLS aggression and is associated with synovial immune cell infiltration. CONCLUSION: Our findings uncover the important roles of NAT10-mediated ac4C modification in promoting rheumatoid synovial aggression and inflammation, indicating that NAT10 may be a potential target for the treatment of RA, even other dysregulated FLSs-associated disorders.

A controlled clinical study on efficacy and safety of periocular triamcinolone acetonide injection for treating ocular myasthenia gravis.

OBJECTIVE: To evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy. METHODS: A total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients. RESULTS: After 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P < 0.001) after treatment. The achievement rates of minimal manifestations status (MMS)for ptosis and ophthalmoplegia after 4 week-treatment were 86.3% and 75%, respectively, while they were 50% and 30% in patients with traditional oral administration. There was statistically significant difference only in MMS (rather than symptom relief rate and generalization conversion rate) between two groups. No serious complications (except for intraorbital hematoma) were found in OMG patients during the treatment period. CONCLUSION: Repeated peribulbar injection of triamcinolone acetonide can effectively alleviate the initial symptoms of OMG patients. However, the evaluation of its long-term efficacy is still needed. CLINICAL TRIAL REGISTRY: This study has been clinically registered by Chinese Clinical Trial Registry (ChiCTR), first trial registration date:05/07/2019, registration number: ChiCTR1900024285.

Analysis of the Nursing Effect of Hemiplegic Limb Rehabilitation Training in the Care of Stroke Patients.

Objective: The objective of this study was to examine the impact of hemiplegic limb rehabilitation training on the nursing care of individuals who have experienced a stroke. Methods: Seventy-six stroke patients from Zhangjiagang Hospital of Traditional Chinese Medicine participated in a study comparing the effects of different nursing interventions. The patients were divided into 2 groups: a control that received standard nursing care and an observation group that received rehabilitation training in addition to standard care. The researchers analyzed the effects on limb movement, daily activities, muscle recovery, and nursing satisfaction between the 2 groups. Results: The nursing intervention in the observation group showed a significantly higher effectiveness rate of 94.74% compared to the control group's rate of 55.26% (P < .05). Prior to the intervention, there was no notable difference in limb movement scores between the 2 groups (P > .05). Similarly, there was no significant difference in Barthel Index scores between the 2 groups before the intervention (P > .05). However, after the intervention, the Bathel Index score in the observation group was significantly higher than that of the control group (P < .05). Conclusion: Hemiplegic limb rehabilitation training nursing care positively impacts stroke patients, improving physical mobility, muscle strength, and overall quality of life. This method should be prioritized and implemented in clinical practice.

Recent advance in modification strategies and applications of soy protein gel properties.

Soy protein gel can be developed into a variety of products, ranging from traditional food (e.g., tofu) to newly developed food (e.g., soy yogurt and meat analog). So far, efforts are still needed to be made on modifying the gel properties of soy protein for improving its sensory properties as animal protein-based food substitutes. Furthermore, there is always a need to regulate its gel properties for designing novel and tailored products of soy protein gels due to the fast-growing plant protein-based product market. This review gave an emphasis on the latest modification strategies and applications of gel properties of soy protein. The modifying methods of soy protein gel properties were reviewed from an aspect of composition or processing. Compositional modification included changing protein composition and gelling conditions and using additives, whereas processing strategies can be achieved through physical, chemical, and enzymatic treatments. Several compositional modification and processing strategies have been both proven to alter the gel properties of soy protein effectively. So far, soy protein gel has been applied in the field of food and biomedicine. In the future, more mechanistic studies on the modification methods are still needed to facilitate the full application of soy protein gel.

Kidney invasion occurred 2 years following liver transplantation for hepatic alveolar echinococcosis: a case report.

BACKGROUND: The organ most commonly invaded in echinococcosis is the liver; the lungs, brain, kidneys, heart, and spleen are rarely invaded, and multi-organ involvement in echinococcosis is even rarer. No studies have reported renal invasion after liver transplantation for hepatic alveolar echinococcosis. CASE PRESENTATION: We report here a case of renal invasion 2 years after allogeneic liver transplantation in a 53-year-old female patient with hepatic alveolar echinococcosis combined with lung metastases. At the time of the first consultation, the lesion had been found to involve the second hepatic hilum combined with lung metastases, but the patient requested conservative treatment, and the lesion was not controlled by taking albendazole for 3 years. After discussion in the treatment group, it was decided to use allogeneic liver transplantation and lung segmental resection for surgical treatment, after which the patient was put on long-term oral immunosuppression. She was hospitalized 2 years later for low back pain and diagnosed with renal alveolar echinococcosis. Due to significant compression and left-sided renal insufficiency, the final option was to remove the diseased kidney. It is worth mentioning that signs of unexplained urinary tract infection were present throughout the course of treatment. CONCLUSION: This study suggests that extra attention should be paid to the presence of cryptogenic lesions in patients with hepatic alveolar echinococcosis who already have definite metastatic lesions. Immunosuppressive drugs after liver transplantation in patients with hepatic echinococcosis may cause occult lesions to develop into active ones. In clinical practice, particular attention should be paid to patients with hepatic alveolar echinococcosis with long-term concomitant signs of unexplained urinary tract infections, which may be a precursor clinical feature of cryptogenic renal alveolar echinococcosis.

Characterization and quantification of chemical constituents in Fuzhuan brick tea using ultra-high-performance liquid chromatography-mass spectrometry.

Fuzhuan brick tea, a distinctive dark tea fermented by microorganisms, is a traditional beverage in China throughout history. Recently, it has attracted considerable attention owing to its unique quality characteristics and potential health benefits. The aim of this study was to establish a method for the quality control of Fuzhuan brick tea for stable production. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to identify Fuzhuan brick tea, and the major components were chosen for further quantitative analysis. Subsequently, a quantification method was developed using ultra-high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry, and its reliability was verified through methodological validation. Finally, a total of 30 compounds were identified, including catechins, flavonoids, alkaloids, and fatty acids. The established method was reliable for methodological validation and was applied to the quantitative analysis of Fuzhuan brick tea. This study provides a fundamental basis for the quality control and further studies on the component analysis of Fuzhuan brick tea.

Metabolomics approach to growth-age discrimination in mountain-cultivated ginseng (Panax ginseng C. A. Meyer) using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Mountain-cultivated ginseng is typically harvested after 10 years, while ginseng aged over 15 years is considered wild ginseng. This study aims to differentiate mountain-cultivated ginseng by age, as the fraudulent practice of selling low-aged cultivated ginseng disguised as high-aged one is damaging the market. In this study, LC-MS analyzed 98 ginseng samples, and multivariate statistical analysis identified patterns between samples to select influential components. Machine learning models were developed to identify ginseng samples of different ages. The untargeted metabolomic analysis clearly divided samples aged 4-20 years into three age groups. Twenty-two potential age-dependent biomarkers were discovered to differentiate the three sample groups. Three machine learning models were used to predict new samples, and the optimal model was selected. Some biomarkers could determine age phases according to the differentiation of mountain-cultivated ginseng samples. These biomarkers were thoroughly analyzed for variation trends. The machine learning models established using the screened biomarkers successfully predicted the age group of new samples.

Clinicopathological features of corneal invasion by filtering bleb.

PURPOSE: To describe the clinicopathological characteristics and explore the possible etiology of cornea invasion by filtering bleb (CIFB) after filtering surgery. METHODS: We reviewed 22 patients treated for CIFB between March 2005 and March 2022. The patients were followed up for more than 1 year. Slit-lamp examination, optical coherence tomography (OCT), ultrasound biomicroscopy, and histopathological examination were performed to observe the morphology of the bleb and depth of corneal invasion. Depending on the severity of the lesion, treatments consisting of local massage, acupuncture separation, or surgical resection were administered. RESULTS: The mean age of the patients was 56.3 ± 8.8 years. All patients underwent filtering surgery in the moderate or advanced stage of glaucoma. The filtering bleb was closely connected with the cornea, and its posterior boundary was locally adhered. Forward displacement of the internal opening of the filtering bleb was found in 4 of 7 surgically treated patients. OCT and pathological examination showed that the filtering blebs invaded the corneal stroma. Removal of the adhesion of the posterior boundary of the filtering bleb by different treatment methods successfully improved the patients' conditions. CONCLUSION: Filtering blebs can invade the corneal stroma. Adhesion of the posterior boundary and forward displacement of the internal opening of the filtering bleb are the possible causes of CIFB. Removal of the adhesion of the posterior boundary of the filtering bleb can halt the progression of CIFB.

Enantioselective effects of paclobutrazol and its enantiomers on glycolipid metabolism in zebrafish (Danio rerio).

Paclobutrazol is a plant growth inhibitor widely used in agricultural production. However, toxicology studies of paclobutrazol enantiomers towards aquatic organisms are limited. Herein, effects of paclobutrazol and its two enantiomers (2R, 3R; 2S, 3S) on glycolipid metabolism of zebrafish have been systemically explored at the concentration of 10 mg/L through biochemical analyses, LC-MS/MS, molecular dynamics simulation, and gene expression. In all treatments, the contents of glucose, citric acid and lactate significantly were increased while the glycogen and pyruvate contents were decreased, in which (2R, 3R)-paclobutrazol exhibited a greater effect than the (2S, 3S)-enantiomer (P < 0.05). Then, activities of hexokinase and lactate dehydrogenase in (2R, 3R)-paclobutrazol treatment were 0.74- and 1.18-fold higher than (2S, 3S)-enantiomer treatment, respectively (P < 0.001), and the results of molecular dynamics simulation revealed that the binding free energy of hexokinase 1 to (2R, 3R)-paclobutrazol was higher than that to the antipode. Moreover, lipids including triglycerides, total cholesterol, fatty acids, bile acids and glycerophospholipids in zebrafish were strikingly affected after paclobutrazol exposure. The (2R, 3R)-paclobutrazol-treated group showed the most obvious changes, indicating that it possessed much stronger disruption ability on the lipid metabolism of zebrafish. Furthermore, qRT-PCR analysis results revealed that (2R, 3R)-enantiomer significantly impacted expressions of glycolipid metabolism-related genes (hk1, g6pc, pck1, pk, aco, cebpa, cyp51, fasn and ppara) in zebrafish than (2S, 3S)-enantiomer (P < 0.05). Briefly, this study provides new evidences for the toxicity of paclobutrazol to aquatic organisms and the potential risk to human health at the chiral level.

Structural Analysis and Characterization of an Antiproliferative Lectin from Canavalia villosa Seeds.

Cells use glycans to encode information that modulates processes ranging from cell-cell recognition to programmed cell death. This information is encoded within a glycocode, and its decoding is performed by carbohydrate-binding proteins. Among these, lectins stand out due to their specific and reversible interaction with carbohydrates. Changes in glycosylation patterns are observed in several pathologies, including cancer, where abnormal glycans are found on the surfaces of affected tissues. Given the importance of the bioprospection of promising biomolecules, the current work aimed to determine the structural properties and anticancer potential of the mannose-specific lectin from seeds of Canavalia villosa (Cvill). Experimental elucidation of the primary and 3D structures of the lectin, along with glycan array and molecular docking, facilitated the determination of its fine carbohydrate-binding specificity. These structural insights, coupled with the lectin's specificity, have been combined to explain the antiproliferative effect of Cvill against cancer cell lines. This effect is dependent on the carbohydrate-binding activity of Cvill and its uptake in the cells, with concomitant activation of autophagic and apoptotic pathways.

Environmental, social, and governance (ESG) performance and financial outcomes: Analyzing the impact of ESG on financial performance.

BACKGROUND: Environmental Social Governance (ESG) investment had entered a phase of rapid development in the past few decades as most nations had put forward "carbon neutral" initiatives. ESG would receive more attention from the industry and academia in a global environment full of uncertainties. Companies benefit from the sharing of ESG data by improving their brand image, which attracts funding, lowers financing costs, and increases valuation. PURPOSE: To explore how ESG drives corporate financial performance. Also, the research examines the interrelation of ESG presentation and corporate presentation. DESIGN: /methodology/approach: Over an interval of 10 years (2011-2020) using a sample of 3332 listed organizations worldwide. The theory of the research is on the basis of stakeholder and transmitting signal theory and multiple regression and categorized regression were applied with STATA 16.0 software. RESULTS: The study utilizes a large dataset of 24,076 valid observations, providing robust statistical power for the analysis. The study findings proved that ESG performance is positively interrelated with corporate performance (p < 0.01). According to the findings of the study, at 1% of the level related to significance (p < 0.01), the regression coefficient for ESG is considerably positive. Thus, the influence of ESG rating on corporate performance is significant for large-scale companies and insignificant for small-scale companies. The results demonstrate that the positive impact of ESG rating on corporate financial performance is more pronounced in the high risk case than in the low risk case (p < 0.01). The results highlight the importance of ESG performance in today's world. Overall, the study gives precious perception about the interrelation between ESG and corporate financial performance (CFP). POLICY IMPLICATIONS: The researchers believe that the results of this study are beneficial to companies and governments in the development of environmentally conscious industries since they demonstrate corporate success through ESG. More realistically, the ESG can boost corporate firm performance by enabling businesses to maintain sustainability, establish a solid reputation, win the trust of stakeholders, and contribute to solving national sustainable development issues. Additionally, the researchers believe that the results of this study can boost management effectiveness, which in turn can help firms succeed. ORIGINALITY/VALUE: In the context of environmentally sensitive industries, this study findings provide empirical insights to the association between the corporate firms success and ESG performance. In addition, the findings provide insights to the business organizations development and the significance of ESG integration in the business organizations.

Chromium Picolinate Protects against Testicular Damage in STZ-Induced Diabetic Rats via Anti-Inflammation, Anti-Oxidation, Inhibiting Apoptosis, and Regulating the TGF-ß1/Smad Pathway.

Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes.

[Application Value of Novel Coagulation Markers in Predicting Postoperarative Complications in the Early Stage After Liver Transplantation].

Objective: To investigate the relationship between thrombin-antithrombin complex (TAT), plasmin-α 2-plasmininhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC) and postoperative complications in the early stage after liver transplantation (LT). Methods: We analyzed the perioperative clinical data, including plasma TAT, PIC, sTM, and tPAIC, of 130 post-LT patients admitted to the intensive care unit (ICU), West China Hospital, Sichuan University between December 2021 and November 2022. Patients were divided into two groups, a complication group and a non-complication group, according to whether they experienced complications of Clavien-Dindo (CD) grade Ⅲb and above within 30 days after the surgery. Univariate analysis and binary multivariate logistic regression models were used to determine the risk factors for complications within 30 days post-LT. Results: The incidence of complications of CD grade Ⅲb and above within 30 days post-LT was 33.1% (43/130). Patients in the complication group had significantly higher scores for the Model for End-Stage Liver Disease (MELD), operative time, intraoperative red blood cell transfusion volume, intraoperative plasma transfusion volume, and plasma TAT, PIC, sTM and tPAIC measured at the time of admission to ICU after the operation than those in the non-complication group did (all P<0.05). Logistic regression showed that for every single U of red blood cells transfused during the transplant surgery, the probabilities of complications within 30 days post-LT increased by 15.1% (95% confidence interval [ C I]: 1.070-1.239, P<0.001) and for the increase of every single TU/mL of plasma sTM measured upon post-LT admission to ICU, the probabilities of complications increased by 13.7% (95% CI: 1.060-1.220, P<0.001). Conclusion: Plasma sTM measured upon admission to ICU after LT is an independent risk factor for complications within 30 days post-LT, and additional assessment of sTM may help predict complications in the early stage post-LT.

[Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome].

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, ß-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Bio-nanocomplexes with autonomous O2 generation efficiently inhibit triple negative breast cancer through enhanced chemo-PDT.

As one kind of aggressive cancer, triple-negative breast cancer (TNBC) has become one of the major causes of women mortality worldwide. Recently, combinational chemo-PDT therapy based on nanomaterials has been adopted for the treatment of malignant tumor. However, the efficacy of PDT was partly compromised under tumor hypoxia environment due to the lack of sustainable O2 supply. In this study, CeO2-loaded nanoparticles (CeNPs) with peroxidase activity were synthesized to autonomously generate O2 by decomposing H2O2 within tumor region and reprogramming the hypoxia microenvironment as well. Meanwhile, the compound cinobufagin (CS-1) was loaded for inhibiting TNBC growth and metastasis. Moreover, the hybrid membrane camouflage was adopted to improve the biocompatibility and targeting ability of nanocomplexes. In vitro assay demonstrated that decomposition of H2O2 by CeO2 achieved sustainable O2 supply, which accordingly improved the efficacy of PDT. In turn, the generated O2 improved the cytotoxicity and anti-tumor migration effect of CS-1 by downregulating HIF-1α and MMP-9 levels. In vivo assay demonstrated that the combination of CS-1 and PDT significantly inhibited the growth and distance metastasis of tumor in MDA-MB-231 bearing mice. Thus, this chemo-PDT strategy achieved satisfactory therapeutic effects by smartly utilizing the enzyme activity of nanodrugs and special micro-environment of tumor.

Serum IGF-1 levels are associated with sarcopenia in elderly men but not in elderly women.

BACKGROUND: Sarcopenia is an age-associated decline in muscle mass that negatively affects the metabolic rate, strength, and function of the body and ultimately leads to a decrease in quality of life. Insulin-like growth factor 1 (IGF-1) is a modulator of muscle mass and muscle function. There is evidence that IGF-1 is related to the appendicular skeletal muscle mass index (ASMI) and grip strength. The aim of this study was to explore the relationship between serum IGF-1 levels and sarcopenia in older people. METHODS: In this cross-sectional survey of 984 people older than 60 years old, we used the 2019 criteria of the Asian Working Group for Sarcopenia (AWGS) to define sarcopenia. We collected demographic variables, measured ASMI and grip strength, and detected serum IGF-1 data. The levels of serum IGF-1 were separated into quintiles (Q1-Q5). RESULTS: Adjusted for age, education level, smoking, number of diseases and BMI, the multivariable linear regression analysis revealed that serum IGF-1 levels were related to ASMI in elderly men (coefficient = 0.03, 95% CI = 0.02-0.05, P < 0.001) but were not related to their grip strength. There was no significant relationship between serum IGF-1 levels and ASMI or grip strength in elderly women. The multivariable log-binomial regression analysis showed that higher serum IGF-1 levels were associated with a lower prevalence of sarcopenia in elderly men (prevalence ratio (PR) = 0.99, 95% CI = 0.98-1.00, P < 0.05) but not in elderly women. CONCLUSION: Serum IGF-1 levels were highly correlated with sarcopenia in older men. Further studies are needed to further explore the possible reasons for the observed difference between genders. Serum IGF-1 might predict sarcopenia prevalence in elderly men.

CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression.

BACKGROUND: An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma. METHODS: RNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression. RESULTS: The downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis. CONCLUSIONS: CircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.

Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI.

PURPOSE: To evaluate the value of gadobenate dimeglumine-enhanced MRI in predicting the pathologic grade of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with pathologically proven HCC who underwent preoperative gadobenate dimeglumine-enhanced dynamic MRI were included. Two radiologists blinded to pathology results evaluated images in consensus. Lesions were evaluated quantitatively in terms of ratio of enhancement (RE), and qualitatively based on image features related to tumor aggressiveness. Logistic regression and ROC analyses were used to determine the value of these parameters to predict pathologic grade. RESULTS: In total, 221 patients (194 males, 27 females, aged 52.9 ± 11.7 years) with 49 poorly differentiated HCCs and 172 well/moderately differentiated HCCs were evaluated. Features significantly related to poorer pathologic grade at univariate analysis included lower RE in the early arterial phase (EAP) (p = 0.001), nonsmooth margins (p = 0.001), absence of capsule (p < 0.001), arterial peritumoral hyperenhancement (p < 0.001), higher AFP (p = 0.004), multiple tumors (p = 0.026), and larger tumor size (p = 0.028). At multivariate analysis, lower RE (EAP) (OR = 0.144, p = 0.002), absence of capsule (OR = 0.281, p = 0.004), and arterial peritumoral hyperenhancement (OR = 4.117, p < 0.001) were independent predictive factors for poorer pathologic grade. ROC analysis showed lower RE (EAP) was predictive of poorer pathologic grade (AUC = 0.667). AUC increased to 0.797 when combined with absence of capsule and presence of peritumoral hyperenhancement. CONCLUSIONS: Lower RE (EAP), absence of capsule, and arterial peritumoral hyperenhancement were predictive biomarkers for poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. KEY POINTS: • Gadobenate dimeglumine-enhanced dynamic MRI was a useful quantitative biomarker for preoperative prediction of pathologic grade in patients with HCC. • Lower RE in the early arterial phase, absence of capsule, and arterial peritumoral hyperenhancement were potential imaging indicators for preoperative prediction of poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced MRI. • A lower RE in the early arterial phase was effective at predicting poorer pathologic grade of HCCs but prediction is improved when combined with absence of capsule and presence of peritumoral hyperenhancement.