Arctium lappa L. polysaccharides enhanced the therapeutic effects of nasal ectomesenchymal stem cells against liver fibrosis by inhibiting the Wnt/ß-catenin pathway.

The oxidative microenvironment in fibrotic livers often diminishes the effectiveness of mesenchymal stem cells (MSCs)-based therapy. Recent research suggests that pharmacological pre-treatment could enhance the therapeutic performance of MSCs. In this study, we assessed the impact of Arctium lappa L. polysaccharides (ALP) on the biological properties of nasal ectomesenchymal stem cells (EMSCs) and investigated the augmenting effect of ALP pretreatment on EMSCs (ALP-EMSCs) for the treatment of liver fibrosis. ALP treatment demonstrated multiple biological impacts on EMSC functions regarding liver fibrosis: firstly, it maintained the stemness of the cells while boosting the EMSCs' paracrine effects; secondly, it increased the expression of anti-inflammatory and antioxidant factors; thirdly, it inhibited the activation of hepatic stellate cells (HSCs) and liver collagen build-up by modulating the Wnt/ß-catenin signaling pathways. Collectively, these effects helped to halt the progression of liver fibrosis. Therefore, the use of ALP-EMSCs presents an innovative and promising approach for treating hepatic fibrosis in clinical scenarios.

Effects of repeated low-level red-light therapy on macular retinal thickness and microvascular system in children with myopia.

OBJECTIVE: The objective of the study was to use optical coherence tomography angiography (OCTA) to analyze the effects of repeated low-level red-light (LLLT) therapy on macular retinal thickness and the microvascular system in children with myopia to evaluate the safety of this therapy. METHODS: This prospective study included 40 school-age children with myopia (80 eyes), aged 7-14 years, who received therapy using a LLLT instrument. At baseline and therapy for 1 month, 3 months, 6 months, all children underwent comprehensive ophthalmological examinations, including slit-lamp examination, uncorrected visual acuity, best-corrected visual acuity, spherical equivalent degree, axial length, and OCTA. The vessel densities of the superficial retinal capillary plexus, macular inner retinal thickness, and full-layer retinal thickness were measured. RESULTS: The macular inner retinal thickness increased at 1 month and remained unchanged thereafter, It differed significantly in nine areas at 1, 3, and 6 months compared to the thicknesses before therapy (P < 0.05); however, we observed no significant differences between the different time points (P > 0.05). The macular full-layer retinal thickness increased at 1 month and remained unchanged thereafter; the changes showed significant differences at 1 month and 3 months compared to before therapy, for the inner nasal region (P < 0.05). The other eight areas showed significant differences at 1, 3, and 6 months compared with before therapy (P < 0.05); however, no significant difference was observed between the different time points after therapy (P > 0.05). The vessel density of the superficial retinal capillary plexus did not differ significantly among the four groups (P > 0.05). CONCLUSIONS: LLLT therapy was safe. The school-aged children exhibited macular thickening after LLLT therapy, which had no significant effect on macular microcirculation.

Quantitative analysis of optic disc changes in school-age children with ametropia based on artificial intelligence.

AIM: To explore changes in the optic disc and peripapillary atrophy (PPA) in school-age children with ametropia using color fundus photography combined with artificial intelligence (AI) technology. METHODS: Based on the retrospective case-controlled study, 226 eyes of 113 children aged aged 6-12y were enrolled from October 2021 to May 2022. According to the results of spherical equivalent (SE), the children were divided into four groups: low myopia group (66 eyes), moderate myopia group (60 eyes), high myopia group (50 eyes) and emmetropia control group (50 eyes). All subjects underwent un-aided visual acuity, dilated pupil optometry, best-corrected visual acuity (BCVA), intraocular pressure, ocular axis measurement and color fundus photography. RESULTS: The width of PPA, horizontal diameter ratio of PPA to the optic disc and area ratio of PPA to the optic disc were significantly different among the four groups (P<0.05). The width of the nasal and temporal neuroretinal rim, the roundness of the optic disc, the height of PPA, the vertical diameter ratio of PPA to the optic disc, and the average density of PPA in the high myopia group were significantly different compared with the other three groups (P<0.05). There were strong negative correlations between SE and area ratio of PPA to the optic disc (r=-0.812, P<0.001) and strong positive correlation between axial length (AL) and area ratio of PPA to the optic disc (r=0.736, P<0.001). CONCLUSION: In school-age children with high myopia, the nasal and temporal neuroretinal rims are narrowed and even lost, which have high sensitivity. The area ratio of the PPA to the optic disc could be used as an early predictor of myopia progression, which is of great significance for the development prevention and management of myopia.

Arctium lappa L. root polysaccharides ameliorate CCl4-induced acute liver injury by suppressing oxidative stress, inflammation and apoptosis.

In this study, water-soluble polysaccharides purified from burdock root were used to intervene in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) of BRL3A hepatocytes and rats. Our results indicated that CCl4 significantly inhibited hepatocyte viability and upregulated the expression of reactive oxygen species (ROS), malondialdehyde (MDA), pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), and the pro-apoptotic protein Bax. However, Arctium lappa L. root polysaccharides (ALP) could effectively ameliorate liver function and histopathology, oxidative stress, and inflammatory markers. In addition, ALP reduced the expression of apoptotic markers and promoted the proliferation of damaged hepatocytes. In conclusion, ALP possesses a hepatoprotective effect mediated by attenuating oxidative damage, inflammation and apoptosis in ALI.

A new model based on gamma-glutamyl transpeptidase to lymphocyte ratio and systemic immune-inflammation index can effectively predict the recurrence of hepatocellular carcinoma after liver transplantation.

Background: Liver transplantation (LT) is one of the most effective treatment modalities for hepatocellular carcinoma (HCC), but patients with HCC recurrence after LT always have poor prognosis. This study aimed to evaluate the predictive value of the gamma-glutamyl transpeptidase-to-lymphocyte ratio (GLR) and systemic immune-inflammation index (SII) in terms of HCC recurrence after LT, based on which we developed a more effective predictive model. Methods: The clinical data of 325 HCC patients who had undergone LT were collected and analyzed retrospectively. The patients were randomly divided into a development cohort (n = 215) and a validation cohort (n = 110). Cox regression analysis was used to screen the independent risk factors affecting postoperative recurrence in the development cohort, and a predictive model was established based on the results of the multivariate analysis. The predictive values of GLR, SII and the model were evaluated by receiver operating characteristic (ROC) curve analysis, which determined the cut-off value for indicating patients' risk levels. The Kaplan-Meier survival analysis and the competing-risk regression analysis were used to evaluate the predictive performance of the model, and the effectiveness of the model was verified further in the validation cohort. Results: The recurrence-free survival of HCC patients after LT with high GLR and SII was significantly worse than that of patients with low GLR and SII (P<0.001). Multivariate Cox regression analysis identified GLR (HR:3.405; 95%CI:1.954-5.936; P<0.001), SII (HR: 2.285; 95%CI: 1.304-4.003; P=0.004), tumor number (HR:2.368; 95%CI:1.305-4.298; P=0.005), maximum tumor diameter (HR:1.906; 95%CI:1.121-3.242; P=0.017), alpha-fetoprotein level (HR:2.492; 95%CI:1.418-4.380; P=0.002) as independent risk factors for HCC recurrence after LT. The predictive model based on these risk factors had a good predictive performance in both the development and validation cohorts (area under the ROC curve=0.800, 0.791, respectively), and the performance of the new model was significantly better than that of single GLR and SII calculations (P<0.001). Survival analysis and competing-risk regression analysis showed that the predictive model could distinguish patients with varying levels of recurrence risk in both the development and validation cohorts. Conclusions: The GLR and SII are effective indicators for evaluating HCC recurrence after LT. The predictive model based on these indicators can accurately predict HCC recurrence after LT and is expected to guide preoperative patient selection and postoperative follow-up.

Therapeutic Efficiency of Nasal Mucosa-Derived Ectodermal Mesenchymal Stem Cells in Rats with Acute Hepatic Failure.

Background: Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear. Methods: EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl4-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro. Results: EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the liver's microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea. Conclusions: These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering.

Bacterial metabolism-triggered-chemiluminescence-based point-of-care testing platform for sensitive detection and photothermal inactivation of Staphylococcus aureus.

Post-operative pathogenic infections in liver transplantation seriously threaten human health. It is essential to develop novel methods for the highly sensitive and rapid detection of Staphylococcus aureus (S. aureus). Interestingly, the combination of the property of bacteria to secrete hydrogen peroxidase, bacterial metabolism-triggered-chemiluminescence (CL)-based bioassays can be as a candidate point-of-care testing (POCT) for the detection of S. aureus against the CL substrate Luminol and hydrogen peroxide without excitation light sources. Here, a CL-based strategy with stable and visualized CL intensity was fabricated according to a hybrid biomimetic enzyme of copper-Hemin metal-organic framework, which enhances the biological enzyme activity while improving the stability and sensitivity of the assay. By further integrating S. aureus-specific capture and one-step separation of the antibody-modified Fe3O4 NPs (Fe3O4 NPs@Ab), the portable device integrated smartphone enables CL-based POCT for specific detection of S. aureus in the range of 101-106 CFU/mL with a limit of detection as low as 1 CFU/mL. Specifically, S. aureus can be eliminated after detection with high antibacterial efficiency due to the excellent photothermal properties of Fe3O4 NPs@Ab. The developed multifunctional platform has the advantages of simplicity of operation and low cost, indicating great potential in clinical applications.

miR-187-3p increases gemcitabine sensitivity in breast cancer cells by targeting FGF9 expression.

Breast cancer is the most common type of malignancy in women, which remains a significant health concern worldwide. Gemcitabine is a frequently applied anticancer pharmacological agent. However, the efficacy of gemcitabine is limited by chemoresistance. In the present study, a combination of reverse transcription quantitative-PCR, cell viability, flow cytometry, luciferase reporter assay and western blot analysis were performed to elucidate the potential effects of miR-187-3p on gemcitabine sensitivity in the breast cancer cell line, MDA-MB-231. The results revealed that miR-187-3p was significantly decreased in the breast cancer tumor tissues. Moreover, the overexpression of miR-187-3p significantly inhibited cell viability and promoted apoptosis in MDA-MB-231 cells. In addition, miR-187-3p overexpression enhanced the anti-proliferative and pro-apoptotic effects of gemcitabine, indicating that miR-187-3p regulated gemcitabine sensitivity in breast cancer cells. Mechanistically, miR-187-3p negatively regulated the expression of fibroblast growth factor 9 (FGF9) by binding to its 3'-untranslated region. Overexpression of FGF9 reversed the aforementioned effects of miR-187-3p overexpression on cell viability and apoptosis in the presence of gemcitabine. In conclusion, the present study indicated that miR-187-3p increased gemcitabine sensitivity in breast cancer cells by targeting FGF9 expression.

Aqueous Extracts of Cordyceps kyushuensis Kob Induce Apoptosis to Exert Anticancer Activity.

Cancer has become the leading cause of mortality since 2010 in China. Despite the remarkable advances in cancer therapy, a low survival rate is still a burden to the society. The antineoplastic activity of aqueous extracts of Cordyceps kyushuensis Kob (AECK) was measured in this study. Results showed that AECK can significantly inhibit the proliferation and viability of U937 and K562 when treated with different concentrations of AECK, and the IC50 values of U937 and K562 were 31.23 µg/ml and 62.5 µg/ml, respectively. Hoechst 33258 staining showed that AECK could cause cell shrinkage, chromatin, condensation, and cytoplasmic blebbing, and DNA ladder experiment revealed the evident feature of DNA fragmentation which showed that AECK could induce cell apoptosis. Moreover, AECK gave rise to intrinsic apoptosis through increasing the amount of Ca2+ and downregulating the expression of Bcl-2. Meanwhile, the level of Fas death receptor was elevated which indicated that AECK could lead to exogenous apoptosis in U937. The expressions of oncogene c-Myc and c-Fos were suppressed which manifested that AECK could negatively regulate the growth, proliferation, and tumorigenesis of U937 cells. This research presented the primary antitumor activity of AECK which would contribute to the widely use of Cordyceps kyushuensis Kob as a functional food and medicine.

Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells.

Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8. And ectopic expression of c-FLIPL dramatically prevented cordycepin-caused apoptosis. Meanwhile, cordycepin stimulated autophagy through suppressing mTOR signaling pathway in lung cancer cells. When autophagy was blocked by Atg5 siRNA or PI3K inhibitor LY294002, the levels of apoptosis caused by cordycepin were obviously attenuated. In addition, suppression of autophagy could also elevate the level of c-FLIPL which indicated cordycepin-triggered autophagy promoted the degradation of c-FLIPL. Therefore, we conclude that cordycepin induces apoptosis through autophagy-mediated downregulation of c-FLIPL in human NSCLC cells. Taken together, our findings provide a novel prospect on the anti-tumor property of cordycepin, which may further prompt cordycepin to serve as a promising therapeutic approach in NSCLC treatment.