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Interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α) play important roles in epithelial-mesenchymal transformation (EMT) and tumor development. Previous studies have demonstrated that IL-6 promotes EMT, invasion, and metastasis in epithelial ovarian cancer (EOC) cells by activating the STAT3/HIF-1α pathway. MicroRNA (miRNA) is non-coding small RNAs that also play an important role in tumor development. Notably, Let-7 and miR-200 families are prominently altered in EOC. However, whether IL-6 regulates the expression of Let-7 and miR-200 families through the STAT3/HIF-1α signaling to induce EMT in EOC remains poorly understood. In this study, we conducted in vitro and in vivo investigations using two EOC cell lines, SKOV3, and OVCAR3 cells. Our findings demonstrate that IL-6 down-regulates the mRNA levels of Let-7c and miR-200c while up-regulating their target genes HMGA2 and ZEB1 through the STAT3/HIF-1α signaling in EOC cells and in vivo. Additionally, to explore the regulatory role of HIF-1α on miRNAs, both exogenous HIF blockers YC-1 and endogenous high expression or inhibition of HIF-1α can be utilized. Both approaches can confirm that the downstream molecule HIF-1α inhibits the expression and function of Let-7c and miR-200c. Further mechanistic research revealed that the overexpression of Let-7c or miR-200c can reverse the malignant evolution of EOC cells induced by IL-6, including EMT, invasion, and metastasis. Consequently, our results suggest that IL-6 regulates the expression of Let-7c and miR-200c through the STAT3/HIF-1α pathway, thereby promoting EMT, invasion, and metastasis in EOC cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the risk factors for organoid culture failure in colorectal cancer. Methods: This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples. Results: The median (range) duration of organoid culture was 7 (3-12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant ( P =0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P >0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ 2 =10.773, P =0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ 2 =7.134, P =0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335-0.924, P =0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285-0.820, P =0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154-63.131, P =0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112-61.882, P =0.039) were identified as independent protective factors. Conclusions: The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

Background: Preventing heterologous protein influx in patients is important when using xenogeneic bioartificial livers (BALs) to treat liver failure. The development of transgenic porcine livers synthesizing human proteins is a promising approach in this regard. Here, we evaluated the safety and efficacy of a transgenic porcine liver synthesizing human albumin (hALB) and coagulation factor VII (hFVII) within a bioartificial system., Methods: Tibetan miniature pigs were randomly subjected to different interventions after surgery-induced partially ischemic liver failure. Group A (n = 4) was subjected to basic treatment; group B (n = 4) was to standard medical treatment and wild-type porcine BAL perfusion, and group C (n = 2) was to standard medical treatment and transgenic BAL perfusion. Biochemical parameters, coagulation status, survival time, and pathological changes were determined. Expressions of hALB and hFVII were detected using immunohistochemistry and enzyme-linked immunosorbent assays., Results: The survival time in group A was 9.75 ± 1.26 days; this was shorter than that in both perfused groups, in which all animals reached an endpoint of 12 days (P = 0.006). Ammonia, bilirubin, and lactate levels were significantly decreased, whereas albumin and fibrinogen levels were increased after perfusion (all P < 0.05). hALB and hFVII were detected in transgenic BAL-perfused pig serum and ex vivo in the liver tissues., Conclusions: The humanized transgenic pig livers could synthesize and secrete hALB and hFVII ex vivo in a whole organ-based bioartificial system, while maintaining their metabolism, detoxification, transformation, and excretion functions, which were comparable to those observed in wild-type porcine livers. Therefore, the use of transgenic bioartificial whole livers is expected to become a new approach in treating acute liver failure., (Copyright © 2022. Published by Elsevier B.V.)

In this Letter, we propose a scheme to achieve a nonreciprocal conventional photon blockade in a nonlinear device consisting of an atom and spinning cavity by manipulating the detuning between the atom and the cavity. We show that the single-photon blockade can be generated by driving the spinning resonator from one side, while photon-induced tunneling is driven by the other side with the same driving strength. This nonreciprocal conventional photon blockade effect originates from the Fizeau-Sagnac drag, which leads to different splitting of the resonance frequencies for the counter-circulating modes. We give four optimal solutions for Fizeau-Sagnac shifts to generate a nonreciprocal conventional photon blockade with the arbitrary detunings between atom and cavity.

This study is designed to investigate the function of the miR-145 in the protection of neural stem cells (NSCs) through targeting mitogen-activated protein kinase (MAPK) pathway in the treatment of cerebral ischemic stroke rat. In our study, rat NSCs were selected and cultured in complete medium. The light microscopy was used to observe the morphology of NSCs at different times. The quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR) was used to detect the miR-145 and other related mRNAs of the MARK pathway. The Western blotting was used to detect the activation of MAPK pathway and neuronal specific markers. The Immunofluorescence was used to detect the expression of the neuron-specific enolase. And the cell viability was detected by Cell Counting Kit (CCK)-8 assay. The flow cytometry was used to test the cell cycle and apoptosis. The ischemic stroke rat models were established and neural stem cell transplantation was performed. The neurological function score, balance beam experiment, and cortical Nissl staining were used to evaluate the postoperative neurological function in rats. The expression of miR-145, extracellular signal-regulated kinase (ERK), and p38 mRNA in rat NSCs increased in a time-dependent manner. Compared with the Blank group, the over-expression of miR-145 promoted the expression of related mRNA and protein of the MAPK pathway in NSCs, while the decreased expression of miR-145 suppressed the MAPK Pathways. Compared with the Blank group, over-expression of miR-145 in NSCs promoted the up-regulation of Cyclin D1, Nestin, neuron-specific enolase (NSE), and Glial fibrillary acidic protein (GFAP) proteins, enhanced the activity of NSCs, and promoted cell proliferation and differentiation, while inhibited the cell apoptosis and the Cleaved-caspase 3 expression. After treatment of NSCs in the SB203580 group, the Nestin, NSE, and GFAP were decreased; cell viability, proliferation and differentiation were inhibited, while Cleaved-caspase 3 protein and cell apoptosis rate increased. The results of animal experiments showed that compared with the Blank group, the walking ability and neurological impairment recovered rapidly in the rats after transplantation of NSCs with over-expression of miR-145, and more neurons were generated in the cortex. After the transplantation of SB203580-treated NSCs, the walking ability and neurological impairment of the rats were slower and the cortical neurons were less. We conclude that miR-145 protects the function of neuronal stem cells through targeting MAPK pathway in the treatment of cerebral ischemic stroke rat., (Copyright © 2018. Published by Elsevier Inc.)

Background: Patients with metastatic colorectal cancer (mCRC) often suffer from progressive disease despite previous therapy. It has been a great challenge for those patients. In 2012, regorafenib was approved for mCRC. In this meta-analysis, we aimed to collect and present existing data to explorethe clinical use of regorafenib., Methods: The online electronic databases, such as PubMed, Embase, and the Cochrane library, updated to November 2017 were systematically searched. Trials on the effectiveness of regorafenib in patients who suffer from treatment-refractory metastatic colorectal cancer were included, of which the main outcomes included 3 parameters: overall survival (OS), progression-free survival (PFS), and grade 3/4 AE., Results: Totally, 4 trials were included in this meta-analysis. The OD was significantly better with the use of regorafenib (OR = 0.78, 95%CI = 0.65-0.94, I = 69%, P = .008), and PFS (OR = 0.52, 95%CI = 0.34-0.79, I = 97%, P = .002). However, the most common toxicities occurred more frequently in the regorafenib group than the control group (OR = 3.73, 95%CI = 1.68-8.28, I = 79%, P = .001)., Conclusion: Regorafenib demonstrates better efficacy and has manageable adverse-event profile for treatment-refractory mCRC. Considering the safety feature of regorafenib, further studies and clinical trials are warranted to investigate the dosing of regorafenib and alternative approaches are needed to explore predictive biomarker fortherapy selection.

Objective: Ambulatory arterial stiffness index (AASI) has been recently proposed to reflect the dynamic relation between diastolic and systolic blood pressure throughout the whole day. The aim of our study was to investigate the change in AASI with advancing age and the correlation with 24 hours pulse pressure (24 h PP) in healthy individuals., Methods: 246 healthy subjects [mean age (59.7 +/- 14.6) years, women 38.6%] underwent 24 hours ambulatory blood pressure monitoring (ABPM) in normal life style. The blood pressure recordings, heart rate (HR), mean arterial pressure (MAP) and pulse pressure (PP) were analyzed simultaneously by computer for every 30 minutes during 6:00 am-22:00 pm and every 60 minutes during 22:00 pm-6:00 am. Using all the blood pressure recordings, we plotted diastolic against systolic blood pressure from each individuals and calculated the regression slope. AASI was derived from 1 minus this regression slope., Results: In 246 healthy individuals, AASI increased with age. Among the healthy individuals, the 95th percentile of AASI was 0.56, the upper boundary of the 95% prediction interval of AASI in relation to age were 0.49 at 20 - 39 years, 0.59 at 40 - 59 years, 0.69 at 60 - 79 years, 0.79 at > or = 80 years. The correlation coefficient between AASI and 24 h PP was 0.497 (P < 0.01). AASI linearly increased with age in healthy individuals, whereas the relation between pulse pressure and age was curvilinear., Conclusions: AASI as a index reflecting blood pressure relationship, manifested the corresponding change with advancing age. The correlation between AASI and traditional index 24 h PP indicated AASI as a new measure of arterial stiffness.