Identification of Panax notoginseng origin using terahertz precision spectroscopy and neural network algorithm.

Panax notoginseng (P. notoginseng), a Chinese herb containing various saponins, benefits immune system in medicines development, which from Wenshan (authentic cultivation) is often counterfeited by others for large demand and limited supply. Here, we proposed a method for identifying P. notoginseng origin combining terahertz (THz) precision spectroscopy and neural network. Based on the comparative analysis of four qualitative identification methods, we chose high-performance liquid chromatography (HPLC) and THz spectroscopy to detect 252 samples from five origins. After classifications using Convolutional Neural Networks (CNNs) model, we found that the performance of THz spectra was superior to that of HPLC. The underlying mechanism is that there are clear nonlinear relations among the THz spectra and the origins due to the wide spectra and multi-parameter characteristics, which makes the accuracy of five-classification origin identification up to 97.62%. This study realizes the rapid, non-destructive and accurate identification of P. notoginseng origin, providing a practical reference for herbal medicine.

An Automatic Method for Sublingual Image Segmentation and Color Analysis.

Automatic segmentation of sublingual images and color quantification of sublingual vein are of great significance to disease diagnosis in traditional Chinese medicine. With the development of computer vision, automatic sublingual image processing provides a noninvasive way to observe patients' tongue and is convenient for both doctors and patients. However, current sublingual image segmentation methods are not accurate enough. Besides, the differences in subjective judgments by different doctors bring more difficulties in color analysis of sublingual veins. In this paper, we propose a method of sublingual image segmentation based on a modified UNet++ network to improve the segmentation accuracy, a color classification approach based on triplet network, and a color quantization method of sublingual vein based on linear discriminant analysis to provide intuitive one-dimensional results. Our methods achieve 88.2% mean intersection over union (mIoU) and 94.1% pixel accuracy on tongue dorsum segmentation, and achieves 69.8% mIoU and 82.7% pixel accuracy on sublingual vein segmentation. Compared with the state-of-art methods, the segmentation mIoUs are improved by 5.8% and 5.3% respectively. Our sublingual vein color classification method has the highest overall accuracy of 81.2% and the highest recall for the minority class of 77.5%, and the accuracy of color quantization is 90.5%.Clinical Relevance- The methods provide accurate and quantified information of the sublingual image, which can assist doctors in diagnosis.

Comparative study of differentiating human pluripotent stem cells into vascular smooth muscle cells in hydrogel-based culture methods.

Vascular smooth muscle cells (VSMCs), which provides structural integrity and regulates the diameter of vasculature, are of great potential for modeling vascular-associated diseases and tissue engineering. Here, we presented a detailed comparison of differentiating human pluripotent stem cells (hPSCs) into VSMCs (hPSCs-VSMCs) in four different culture methods, including 2-dimensional (2D) culture, 3-dimensional (3D) PNIPAAm-PEG hydrogel culture, 3-dimensional (3D) alginate hydrogel culture, and transferring 3-dimensional alginate hydrogel culture to 2-dimensional (2D) culture. Both hydrogel-based culture methods could mimic in vivo microenvironment to protect cells from shear force, and avoid cells agglomeration, resulting in the extremely high culture efficiency (e.g., high viability, high purity and high yield) compared with 2D culture. We demonstrated hPSC-VSMCs produced from hydrogel-based culture methods had better contractile phenotypes and the potential of vasculature formation. The transcriptome analysis showed the hPSC-VSMCs derived from hydrogel-based culture methods displayed more upregulated genes in vasculature development, angiogenesis and blood vessel development, extracellular matrix compared with 2D culture. Taken together, hPSC-VSMCs produced from hydrogel-based culture system could be applied in various biomedical fields, and further indicated the suitable development of alginate hydrogel for industrial production by taking all aspects into consideration.

Responses of well-aquifer system to four earthquakes and implication for contaminant transport in Changan landfill, China.

Evaluation of aquifer response to earthquakes is important to understanding the evolution of aquifer properties and contaminant transport. In Changan Landfill, a multi parameter monitoring system was installed to collect data every 12 h. Principal Component Analysis (PCA), energy density and wavelet analysis, and tidal analysis were used to reveal the response mechanisms to four earthquakes, sensitivity of various parameters to seismic stimuli, and permeability evolution, respectively. The results showed that the chemical characteristics of two aquifers were distinct. The shallow aquifer was polluted by leachate, and the deep aquifer was less polluted. Coseismic responses were dominated by the deep aquifer and the relative contribution of each aquifer remained stable. Coseismic chemical changes were dominated by the opening and closing of fractures, and the long-term evolution was controlled by seasonality. The deep aquifer had a higher sensitivity to seismic stimuli than the shallow aquifer. Tidal analysis showed that a general permeability decrease during this monitoring period reduced contaminant transport, but some contaminants crossed the aquitard between the two aquifers after the Zizhong earthquake, due to an increase in vertical permeability.

TRAF4 Promotes the Proliferation of Glioblastoma by Stabilizing SETDB1 to Activate the AKT Pathway.

The process of ubiquitination regulates the degradation, transport, interaction, and stabilization of substrate proteins, and is crucial for cell signal transduction and function. TNF receptor-associated factor 4, TRAF4, is a member of the TRAF family and is involved in the process of ubiquitination as an E3 ubiquitin protein ligase. Here, we found that TRAF4 expression correlates with glioma subtype and grade, and that TRAF4 is significantly overexpressed in glioblastoma and predicts poor prognosis. Knockdown of TRAF4 significantly inhibited the growth, proliferation, migration, and invasion of glioblastoma cells. Mechanistically, we found that TRAF4 only interacts with the Tudor domain of the AKT pathway activator SETDB1. TRAF4 mediates the atypical ubiquitination of SETDB1 to maintain its stability and function, thereby promoting the activation of the AKT pathway. Restoring SETDB1 expression in TRAF4 knockdown glioblastoma cells partially restored cell growth and proliferation. Collectively, our findings reveal a novel mechanism by which TRAF4 mediates AKT pathway activation, suggesting that TRAF4 may serve as a biomarker and promising therapeutic target for glioblastoma.

Diagnostic Performance of Diffusion Kurtosis Imaging for Benign and Malignant Breast Lesions: A Systematic Review and Meta-Analysis.

Purpose: Magnetic resonance imaging (MRI) has a high sensitivity for differentiating between malignant and non-malignant breast lesions but is sometimes limited due to its low specificity. Here, we performed a meta-analysis to evaluate the diagnostic performance of mean kurtosis (MK) and mean diffusivity (MD) values in magnetic resonance diffusion kurtosis imaging (DKI) for benign and malignant breast lesions. Methods: Original articles on relevant topics, published from 2010 to 2019, in PubMed, EMBASE, and WanFang databases were systematically reviewed. According to the purpose of the study and the characteristics of DKI reported, the diagnostic performances of MK and MD were evaluated, and meta-regression was conducted to explore the source of heterogeneity. Results: Fourteen studies involving 1,099 (451 benign and 648 malignant) lesions were analyzed. The pooled sensitivity, pooled specificity, positive likelihood ratio, and negative likelihood ratio for MD were 0.84 (95% confidence interval (CI), 0.81-0.87), 0.83 (95% CI, 0.79-0.86), 4.44 (95% CI, 3.54-5.57), and 0.18 (95% CI, 0.13-0.26), while those for MK were 0.89 (95% CI, 0.86-0.91), 0.86 (95% CI, 0.82-0.89), 5.72 (95% CI, 4.26-7.69), and 0.13 (95% CI, 0.09-0.19), respectively. The overall area under the curve (AUC) was 0.91 for MD and 0.95 for MK. Conclusions: Analysis of the data from 14 studies showed that MK had a higher pooled sensitivity, pooled specificity, and diagnostic performance for differentiating between breast lesions, compared with MD.

Regulation of Glucose, Fatty Acid and Amino Acid Metabolism by Ubiquitination and SUMOylation for Cancer Progression.

Ubiquitination and SUMOylation, which are posttranslational modifications, play prominent roles in regulating both protein expression and function in cells, as well as various cellular signal transduction pathways. Metabolic reprogramming often occurs in various diseases, especially cancer, which has become a new entry point for understanding cancer mechanisms and developing treatment methods. Ubiquitination or SUMOylation of protein substrates determines the fate of modified proteins. Through accurate and timely degradation and stabilization of the substrate, ubiquitination and SUMOylation widely control various crucial pathways and different proteins involved in cancer metabolic reprogramming. An understanding of the regulatory mechanisms of ubiquitination and SUMOylation of cell proteins may help us elucidate the molecular mechanism underlying cancer development and provide an important theory for new treatments. In this review, we summarize the processes of ubiquitination and SUMOylation and discuss how ubiquitination and SUMOylation affect cancer metabolism by regulating the key enzymes in the metabolic pathway, including glucose, lipid and amino acid metabolism, to finally reshape cancer metabolism.

Rapid On-site identification of geographical origin and storage age of tangerine peel by Near-infrared spectroscopy.

The feasibility of identifying geographical origin and storage age of tangerine peel was explored by using a handheld near-infrared (NIR) spectrometer combined with machine learning. A handheld NIR spectrometer (900-1700 nm) was used to scan the outer surface of tangerine peel and collect the corresponding NIR diffuse reflectance spectra. Principal component analysis (PCA) combined with Mahalanobis distance were used to detect outliers. The accuracies of all models in the anomaly set were much lower than that in calibration set and test set, indicating that the outliers were effectively identified. After removing the outliers, in order to initially explore the clustering characteristics of tangerine peels, PCA was performed on tangerine peels from different origins and the same origin with different storage ages. The results showed that the tangerine peels from the same origin or the same storage age had the potential to cluster, indicating that the spectral data of the same origin or the same storage age had a certain similarity, which laid the foundation for subsequent modeling and identification. However, there were quite a few samples with different origins or different storage ages overlapped and could not be distinguished from each other. In order to achieve qualitative identification of origin and storage age, Savitzky-Golay convolution smoothing with first derivative (SGFD) and standard normal variate (SNV) were used to preprocess the raw spectra. Random forest (RF), K-nearest neighbor (KNN) and linear discriminant analysis (LDA) were used to establish the discriminant model. The results showed that SGFD-LDA could accurately distinguish the origin and storage age of tangerine peel at the same time. The origin identification accuracy was 96.99%. The storage age identification accuracy was 100% for Guangdong tangerine peel and 97.15% for Sichuan tangerine peel. This indicated that the near-infrared spectroscopy (NIRS) combine with machine learning can simultaneously and rapidly identify the origin and storage age of tangerine peel on site.

ZC3H15 promotes glioblastoma progression through regulating EGFR stability.

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved protein involved in several cellular processes, which was responsible for tumorigenesis and may be a promising marker in myeloid leukemia (AML) and hepatocellular carcinoma (HCC). However, little is known about the biological significance and molecular mechanisms of ZC3H15 in GBM. In this study, we revealed that ZC3H15 was overexpressed in GBM and high ZC3H15 expression was associated with poor survival of patients with GBM. We found that ZC3H15 promoted the proliferation, migration, invasion, and tumorigenesis of GBM cells by activating the EGFR signaling pathway. We also revealed that ZC3H15 reduced EGFR ubiquitination, which was responsible for EGFR protein stabilization. In addition, we demonstrated that ZC3H15 inhibited the transcription of CBL, which was an E3 ubiquitin ligase for EGFR proteasomal degradation. And silencing of CBL could partly abrogate the inhibitory effects on cell proliferation, migration, and invasion of GBM cells induced by ZC3H15 knockdown. Thus, our research revealed the important roles of ZC3H15 in GBM development and provided a brand-new insight for improving the treatment of GBMs.

ZC3H15 promotes gastric cancer progression by targeting the FBXW7/c-Myc pathway.

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, which was associated with several cellular processes and was ubiquitously expressed in various human tissues. Recent studies indicated that ZC3H15 was involved in tumorigenesis and may be a potential biomarker in hepatocellular carcinoma (HCC) and acute myeloid leukemia (AML). However, the biological function and molecular mechanism of ZC3H15 in gastric cancer (GC) have not been studied. In this study, we revealed that ZC3H15 was highly expressed in GC and high ZC3H15 expression was closely linked to poor survival of patients with GC. We found that ZC3H15 promoted cell proliferation, migration, and invasion by increasing c-Myc expression. Next, we found that ZC3H15 could modulate c-Myc protein stability by suppressing the transcription of FBXW7, which was mainly responsible for c-Myc degradation. Moreover, silencing of FBXW7 in ZC3H15-knockdown GC cells could partly abrogate the effects induced by ZC3H15 downregulation. Taken together, our data unearth the important roles of ZC3H15 in GC development and suggest that ZC3H15 may be a potential target for the treatment of GC.

An Automatic Petechia Dots Detection Method on Tongue.

Tongue diagnosis with features like tongue coating, petechia, color, size and so on is of great effectiveness and convenience in traditional Chinese medicine. With the development of image processing techniques, automatic image processing can reduce hospital inspection for patients. However, there are ubiquitous problems of inadequate accuracy in petechia dots detection with previous methods. In this paper, we propose a method of petechia dots detection on tongue based on SimpleBlobDetector function in OpenCV library and support vector machines model, which improves the detective accuracy. We test 128 clinic tongue images and select 9 of the images with plentiful petechia dots for further experiments. Our method achieves mean value of false alarm rate 4.6% and missing alarm rate 11.8%, which have 19.4% and 8.2% reduction respectively compared to previous work.Clinical Relevance-The method can provide detailed information of tongue, which assists doctors to investigate curative effect.

A hemocyte-specific cathepsin L-like cysteine protease is involved in response to 20-hydroxyecdysone and microbial pathogens stimulation in silkworm, Bombyx mori.

Cathepsin L protease belongs to the papain-like cysteine proteases family, plays indispensable roles in animals' pathological and physiological processes. However, little is known about Cathepsin L in silkworm, Bombyx mori. Herein, a novel Cathepsin L-like (Cat L-like) was cloned and identified from silkworm by the rapid amplification of cDNA ends (RACE). Cat L-like contains an intact open reading frame (ORF) of 1 668 bp and encodes 556 amino acid residues, consisting of a signal peptide, typical cathepsins' inhibitor_I29, and pept_C1 domain. Cat L-like is specifically and highly expressed in hemocytes. The cathepsin (including Cathepsin L, B, and H) crude extract from hemocytes had typical substrate specific catalytic activities and were sensitive to pH and temperature. Cat L-like up-regulated considerably after 20-hydroxyecdysone (20-E) administration, indicating that Cat L-like may be regulated by insect hormone. The responses of Cat L-like against bacterial infection suggest it may play essential roles in silkworm immunity. Overall, our studies provide a theoretical basis and insights to further investigate the functions of Cat L-like and in insects' innate immunity mechanisms.

C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation.

Numerous factors have been claimed to play important roles in colorectal cancer (CRC) tumorigenesis, including myeloid-derived suppressor cells (MDSCs) and other immune cells, cytokines, and chemokines; however, the precise mechanisms of colorectal tumorigenesis remain elusive, and there is a lack of effective preventive treatments. Here, we investigated the role of complement system, a key regulator of immune surveillance and homeostasis, in colorectal tumorigenesis. Methods: The prototypical CRC model was induced by combined administration of azoxymethane (AOM)/ dextran sulfate sodium (DSS) in Wild-type (WT), C3-, C5-, C5ar1-, and C5ar2-deficient mice. Using flow cytometry, immunohistochemical staining and multiplex bead assay, we profiled the immune cells, cytokines and chemokines. Bone marrow transplantation was employed to determine the contribution of immune cells in colorectal tumorigenesis. Further, we used C5aR1 antagonist PMX205 to investigate the protective role in colorectal tumorigenesis. Results: Complement was extensively activated in inflamed tissues of AOM/DSS-induced murine CRC model, leading to multifaceted consequences. The deficiency of complement C5 or especially C5ar1, but not C3 almost completely prevented CRC tumorigenesis. C5a/C5aR1 signaling recruited MDSCs into the inflamed colorectum to impair CD8+ T cells, and modulated the production of critical cytokines and chemokines, thus initiating CRC. Moreover, the C5aR1 antagonist PMX205 strongly impeded colorectal tumorigenesis. Bone marrow transplantation further revealed that C5aR1 expression by immune cells was critical for colorectal tumorigenesis. Conclusion: Our study identifies C5a/C5aR1 signaling as a vital immunomodulatory program in CRC tumorigenesis and suggests a feasible preventive strategy.

Molecular methylation detection based on terahertz metamaterial technology.

Terahertz wave has a good ability to identify biomolecules due to its fingerprint spectrum characteristics. However, the minimum detectable limit of terahertz technology by the conventional tablet pressing method is on the order of milligrams, which cannot meet the application requirements of low concentration detection in the biomedical field-near or below micrograms. Here, we proposed a method to enhance the detection sensitivity by designing a metamaterial chip with the absorption-induced transparency (AIT) effect, which can enhance the interaction between terahertz waves and biomolecules and lower the detectable limit. Taking 7-methylguanine (7-MG) as an example, based on its terahertz characteristic absorption peak, we designed a split-ring resonator (SRR) metamaterial chip, which has the advantages of high sensitivity, unlabeled detection, fast response and simple measurement. Its quantitative detection limit can reach 6.30 µg, which is about 500 times smaller than that of the traditional tablet pressing method (2.95 mg). In addition, for methylated and unmethylated substances, the chip exhibits different frequency shifts, which also realizes the qualitative identification effectively. These results provide a reference for the rapid and accurate diagnosis of diseases associated with molecular methylation in clinical medicine.

Histone Deacetylase Inhibitor Trichostatin A Suppresses Cell Proliferation and Induces Apoptosis by Regulating the PI3K/AKT Signalling Pathway in Gastric Cancer Cells.

BACKGROUND: Gastric cancer, a common malignant tumour worldwide, has a relatively poor prognosis and is a serious threat to human health. Histone Deacetylase Inhibitors (HDACi) are anticancer agents that are known to affect the cell growth of different cancer types. Trichostatin A (TSA) selectively inhibits the class I and II mammalian Histone Deacetylase (HDAC) family enzymes and regulates many cell processes. Still, the underlying mechanisms of HDACs are not fully understood in gastric cancer. OBJECTIVE: This study aims to investigate the antitumor effect and the mechanism of growth modulation of gastric cancer cells by TSA. METHODS: The cell proliferation of gastric cancer cells was measured by MTT and BrdU immunofluorescence assays. Soft agar assay was used to detect the colony formation ability of gastric cancer cells. Flow cytometry was used to examine cell cycle and apoptosis. Western blot was employed to detect protein expression of target factors. RESULTS: TSA inhibits the proliferation of MKN-45 and SGC-7901 cells and leads to significant repression of colony number and size. Flow cytometry assays show TSA induces cell cycle arrest at G1 phase and apoptosis, and TSA effects the expression of related factors in the mitochondrial apoptotic signalling and cell cycle-related regulatory pathways. Furthermore, TSA increased histone H3K27 acetylation and downregulated the expression of PI3K and p-AKT. CONCLUSION: Downregulating PI3K/AKT pathway activation is involved in TSA-mediated proliferation inhibition of gastric cancer.

PI3K/AKT inhibition reverses R-CHOP resistance by destabilizing SOX2 in diffuse large B cell lymphoma.

Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen, while the remaining therapeutic options are limited. Thus, understanding the underlying mechanisms and developing therapeutic approaches are urgently needed. Methods: We generated two germinal center B cell-like (GCB) and activated B cell-like (ABC) subtype R-CHO resistant DLBCL cell lines, of which the tumor-initiating capacity was evaluated by serial-transplantation and stemness-associated features including CD34 and CD133 expression, side population and ALDH1 activity were detected by flow cytometry or immunoblotting. Expression profiles of these resistant cells were characterized by RNA sequencing. The susceptibility of resistant cells to different treatments was evaluated by in vitro CytoTox-glo assay and in tumor-bearing mice. The expression levels of SOX2, phos-AKT, CDK6 and FGFR1/2 were detected in 12 R-CHOP-resistant DLBCL clinical specimens by IHC. Results: The stem-like CSC proportion significantly increased in both resistant DLBCL subtypes. SOX2 expression level remarkably elevated in both resistant cell lines due to its phosphorylation by activated PI3K/AKT signaling, thus preventing ubiquitin-mediated degradation. Further, multiple factors, including BCR, integrins, chemokines and FGFR1/2 signaling, regulated PI3K/AKT activation. CDK6 in GCB subtype and FGFR1/2 in ABC subtype were SOX2 targets, whose inhibition potently re-sensitized resistant cells to R-CHOP treatment. More importantly, addition of PI3K inhibitor to R-CHOP completely suppressed the tumor growth of R-CHO-resistant DLBCL cells, most likely by converting CSCs to chemo-sensitive differentiated cells. Conclusions: The PI3K/AKT/SOX2 axis plays a critical role in R-CHOP resistance development and the pro-differentiation therapy against CSCs proposed in this study warrants further study in clinical trials for the treatment of resistant DLBCL.

Electrochemical Strategy for Flexible and Highly Conductive Carbon Films: The Role of 3-Dimensional Graphene/Graphite Aggregates.

Conductive carbon films with good flexibility are ever-increasingly desired for electronics. Previous efforts relying on graphene films to achieve this required special treatment to create wrinkles in the lamellar stacking sheet structure. Here, films with a wrinkled structure were facilely fabricated from electrochemically derived 3-dimiensional (3D) graphene/graphite aggregates, exhibiting excellent flexibility and high conductivity. The resulting films are very flexible that can bear 1000 times fold without breakage. A high conductivity up to 100 000 S m-1 can be achieved after a relatively low temperature annealing (1000 °C) owing to its low content of defect and large size of graphene/graphite aggregates. Based on these properties, an electrothermal heater assembled from these composite films supplies a high saturated temperature (423 °C) at low working voltages (4 V). These superior properties, together with the advantage of environmental friendliness and facile and large-scale fabrication, endow the composite films with great potential applications in flexible electronics.

FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression.

OBJECTIVES: We aimed to elucidate the role and molecular mechanisms of FOXM1 in regulating metastasis in oesophageal squamous cell carcinoma (ESCC) as well as its clinical implications. MATERIALS AND METHODS: The expression levels of four isoforms of FOXM1 were analysed by real-time PCR. Next, genetically modification using overexpression and RNAi systems and transwell were employed to examine FOXM1c function in invasion and migration. Dual luciferase and ChIP assays were performed to decipher the underlying mechanism for transcriptional regulation. The expression levels of FOXM1 and IRF1 were determined by immunohistochemistry staining in ESCC specimens. RESULTS: The FOXM1c was predominantly overexpressed in ESCC cell lines compared to the other FOXM1 isoforms. Ectopic expression of FOXM1c promoted invasion and migration of ESCC cells lines, whereas downregulation of FOXM1c inhibited these processes. Moreover, FOXM1c expression was positively correlated with IRF1 expression in ESCC cell lines and tumour specimens. IRF1 is, at least in part, responsible for FOXM1c-mediated invasion and migration. Mechanistically, we identified IRF1 as a transcriptional target of FOXM1c and found a FOXM1c-binding site in the IRF1 promoter region. Furthermore, high expression levels of both FOXM1c and IRF1 were positively associated with low survival rate and predicted a poor prognosis of oesophageal cancer patients. CONCLUSION: FOXM1c promotes the metastasis by transcriptionally targeting IRF1 and may serve as a potential prognostic predictor for oesophageal cancer.

Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling.

Complement activation is involved in the pathogenesis of ischemia reperfusion injury (IRI), which is an inevitable process during kidney transplantation. Therefore, complement-targeted therapeutics hold great potential in protecting the allografts from IRI. We observed universal deposition of C3d and membrane attack complex in human renal allografts with delayed graft function or biopsy-proved rejection, which confirmed the involvement of complement in IRI. Using FB-, C3-, C4-, C5-, C5aR1-, C5aR2-, and C6-deficient mice, we found that all components, except C5aR2 deficiency, significantly alleviated renal IRI to varying degrees. These gene deficiencies reduced local (deposition of C3d and membrane attack complex) and systemic (serum levels of C3a and C5a) complement activation, attenuated pathological damage, suppressed apoptosis, and restored the levels of multiple local cytokines (e.g., reduced IL-1ß, IL-9, and IL-12p40 and increased IL-4, IL-5, IL-10, and IL-13) in various gene-deficient mice, which resulted in the eventual recovery of renal function. In addition, we demonstrated that CRIg/FH, which is a targeted complement inhibitor for the classical and primarily alternative pathways, exerted a robust renoprotective effect that was comparable to gene deficiency using similar mechanisms. Further, we revealed that PI3K/AKT activation, predominantly in glomeruli that was remarkably inhibited by IRI, played an essential role in the CRIg/FH renoprotective effect. The specific PI3K antagonist duvelisib almost completely abrogated AKT phosphorylation, thus abolishing the renoprotective role of CRIg/FH. Our findings suggested that complement activation at multiple stages induced renal IRI, and CRIg/FH and/or PI3K/AKT agonists may hold the potential in ameliorating renal IRI.

CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair.

Radiation therapy is an important treatment modality for esophageal cancer. However, acquisition of radioresistance ultimately results in esophageal cancer relapse. CD59, a membrane-bound complement regulatory protein, can transduce signals via a Src kinase in the lipid raft, thus playing a complement-independent role. However, the effect of CD59 on the esophageal cancer response to ionizing radiation remains unclear. In this study, we found that the expression level of CD59 was positively correlated with the radioresistance of esophageal cancer cell lines and clinical specimens. High CD59 expression indicated poor overall survival (OS) and disease-free survival (DFS) in esophageal squamous cell carcinoma (ESCC) patients who received radiotherapy. Genetic alteration of CD59 expression modulated the radiosensitivity of esophageal cancer cells to ionizing radiation. CD59 deficiency exacerbated DNA damage, hindered cell proliferation, and induced G2/M cell cycle arrest and cellular senescence, leading to an impaired DNA damage repair ability. In addition, CD59 deficiency almost completely reduced the phosphorylation of Src at Y416 despite ionizing radiation. A Src inhibitor saracatinib sensitized esophageal cancer cells to irradiation. Therefore, CD59 may be a potential biomarker for predicting the radioresistance of ESCC to radiotherapy.