Expression patterns of cluster of differentiation 147 impact the prognosis of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)has very low overall survival.According to global cancer statistics,approximately 905677 new cases were reported in 2020,with at least 830180 of them being fatal.Cluster of differentiation 147(CD147)is a novel,transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development.Based on the reports described previously,we theorize that CD147 may be used as a novel biological indicator to predict the prognosis of HCC.To study this possibility,expression profiles of CD147 and corresponding clinical data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed,and a hazard ratio(HR)was established.AIM To explore the pattern of CD147 expression and its applicability in the prognosis of HCC.To establish HRs and probability points for predicting the prognosis of HCC by correlating CD147 expression with clinical characteristics.To determine if CD147 can be a reliable biomarker in HCC prognosis.METHODS The CD147 expression profile in HCC and corresponding clinical data were obtained from TCGA database.The expression patterns of CD147 were then validated by analyzing data from the GEO database.In addition,CD147 immunohistochemistry in HCC was obtained from the Human Protein Atlas.CD147 expression patterns and clinical characteristics in the prognosis of HCC were analyzed by accessing the UALCAN web resource.Accuracy,sensitivity,and specificity of the CD147 expression profile in predictive prognosis were determined by the time-dependent receiver operating characteristic(ROC)curves.Kaplan-Meier curves were plotted to estimate the HR of survival in HCC.Univariate and multivariate Cox regression proportional hazards analyses of CD147 expression levels and clinical characteristics as prognostic factors of HCC were performed.Nomograms were used to establish probability points and predict prognosis.RESULTS Data from TCGA and GEO databases revealed that CD147 was significantly overexpressed in HCC(P=1.624×10^(-12) and P=1.2×10^(-5),respectively).The expression of CD147 and prognosis of HCC were significantly correlated with the clinical characteristics of HCC as per the data from the UALCAN web resource(P<0.05).Kaplan-Meier analysis of CD147 expression in HCC revealed that the high expression groups showed poor prognosis and an HR of survival>1[log-rank test,P=0.000542,HR(in high expression group):1.856,95%confidence interval(CI):1.308 to 2.636].ROC curves were plotted to analyze the 1-year,3-year,and 5-year survival rates.The area under the ROC curve values were 0.675(95%CI:0.611 to 0.740),0.623(95%CI:0.555 to 0.692),and 0.664(95%CI:0.582 to 9.745),respectively.Univariate Cox analysis of CD147 expression and clinical characteristics of HCC and multivariate Cox analysis of CD147 patterns and pathological tumor-node-metastasis stage showed significant differences(univariate Cox,P=0.00013,HR:1.424,95%CI:1.884 to 1.707 and P=0.00066,HR:1.376,95%CI:1.145 to 1.654,respectively;multivariate Cox,P=0.00578,HR:1.507,95%CI:1.126 to 2.018 and P=0.00336,HR:1.443,95%CI:1.129 to 1.844,respectively).Nomograms were plotted to establish the probability points and predict prognosis.The total points ranged from 0 to 180,and the C-index value was 0.673(95%CI:0.600 to 1.000,P<0.01).CONCLUSION Overexpression of CD147 was correlated with poor prognosis in HCC.The CD147 expression profile combined with clinical characteristics can reliably predict the prognosis of HCC.CD147 can serve as a biomarker to predict the prognosis of HCC.

Nε-(carboxymethyl)lysine promotes lipid uptake of macrophage via cluster of differentiation 36 and receptor for advanced glycation end products

BACKGROUND Advanced glycation end products(AGEs)are diabetic metabolic toxic products that cannot be ignored.Nε-(carboxymethyl)lysine(CML),a component of AGEs,could increase macrophage lipid uptake,promote foam cell formation,and thereby accelerate atherosclerosis.The receptor for AGEs(RAGE)and cluster of differentiation 36(CD36)were the receptors of CML.However,it is still unknown whether RAGE and CD36 play key roles in CML-promoted lipid uptake.AIM Our study aimed to explore the role of RAGE and CD36 in CML-induced macrophage lipid uptake.METHODS In this study,we examined the effect of CML on lipid uptake by Raw264.7 macrophages.After adding 10 mmol/L CML,the lipid accumulation in macrophages was confirmed by oil red O staining.Expression changes of CD36 and RAGE were detected with immunoblotting and quantitative real-time polymerase chain reaction.The interaction between CML with CD36 and RAGE was verified by immunoprecipitation.We synthesized a novel N-succinimidyl-4-18Ffluorobenzoate-CML radioactive probe.Radioactive receptor-ligand binding assays were performed to test the binding affinity between CML with CD36 and RAGE.The effects of blocking CD36 or RAGE on CML-promoting lipid uptake were also detected.RESULTS The study revealed that CML significantly promoted lipid uptake by macrophages.Immunoprecipitation and radioactive receptor-ligand binding assays indicated that CML could specifically bind to both CD36 and RAGE.CML had a higher affinity for CD36 than RAGE.ARG82,ASN71,and THR70 were the potential interacting amino acids that CD36 binds to CML Anti-CD36 and anti-RAGE could block the uptake of CML by macrophages.The lipid uptake promotion effect of CML was significantly attenuated after blocking CD36 or RAGE.CONCLUSION Our results suggest that the binding of CML with CD36 and RAGE promotes macrophage lipid uptake.

Vascular Endothelial Growth Factor and Cluster of Differentiation 34 for Assessment of Perioperative Bleeding Risk in Gastric Cancer Patients

Background： Angiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor （VEGF） and cluster of differentiation 34 （CD34） are important signaling proteins involved in angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to tumor progression. This study focused on the relationship between VEGF, CD34, and perioperative hemorrhage in patients with gastric cancer. Methods： To observe the relationship between VEGF and CD34, we tracked 112 patients with advanced gastric cancer for 5 years to assess factors related to hemorrhage, using immunohistochemistry. The results were subjected to statistical analysis using a 2 × 2 contingency table, logistic regression, and receiver operating characteristic （ROC） test. Results： The concentrations of VEGF and CD34 were critically correlated with perioperative hemorrhage and neural invasion in patients with gastric cancer （P 〈 0.05）. Expression of VEGF and CD34 was related （P 〈 0.05, χ2 = 6.834）. VEGF and CD34 co-expression strongly increased the risk of preoperative bleeding （area under the ROC curve 〉0.7, P 〈 0.05）. Conclusions： Expression of VEGF and CD34 was critically correlated with perioperative hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an effective indicator for evaluating the risk ofperioperative bleeding in gastric cancer patients.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Intracranial malignant solitary fibrous tumor metastasized to the chest wall:A case report and review of literature

BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT occurs mainly in the tissue structure of the serosa in the pleura and the thorax,and can be found throughout the body,though extra-thoracic localization,including the cephalic region,is uncommon.We reported the first case of intracranial malignant SFT metastasized to the chest wall.CASE SUMMARY An 81-year-old Japanese man was referred to our hospital due to progressive gait disturbance and appetite loss.His medical history included partial resection due to brain tumor,four times,and 50-Gray radiation therapy at another hospital,starting when he was 74 years old.An unenhanced head computed tomography(CT)scan revealed an 8 cm×5.1 cm×6.5 cm mixed-density mass at the left frontal lobe,accompanying a midline shift,and an unenhanced chest-abdomen CT scan revealed a 6 cm×4.1 cm×6.5 cm low-density mass in the left chest wall.A CT-guided percutaneous lung biopsy was performed,and the pathological findings were SFT corresponding to brain tumor.Finally,the correct diagnosis of his brain tumor in history of past illness revealed to be SFT,and the unremovable tumor,namely present brain lesions enlarged and metastasized to the chest wall.We established a definitive diagnosis of intracranial malignant SFT metastasized to the chest wall.We notified him and his family of the disease,and offered palliative care.He passed away on the 29 th hospital day.CONCLUSION This case suggests the need for careful,detailed examination,and careful followup when encountering patients presenting with a mass.

Biocompatibility of Implantable Electrodes Coated with PVA Films in the Brain of Rats: a Histological Evaluation

The biocompatibility of silicone rubber （SR） based electrodes coating with poly （vinyl alcohol） （PVA） films after implanted in the brain of rats was investigated. Twenty-two Wistar rats were used and implanted with SR electrodes and PVA/PAA films coated electrodes in left and right cerebral cortex respectively. After 4 and 8 weeks, the expression of glial fibrillary acidic protein （GFAP, a specific marker of astrocytes） and cluster of differentiation 68 （CD68, a specific marker of macrophages） were evaluated by immunohistochemistry. After 8 weeks, GFAP and CD68 expressions around PVA electrodes were significantly lower than those around SR electrodes in every stratified area （0-50 μm, 50-100 μm, 100 μm from further up to the electrode-tissue interface）. The resuits show that PVA coating can reduce the expressions of GFAP and CD68, suggesting the PVA coating can improve the biocompatibility of the SR while it is implanted in brain.

Application of Flow Cytometry in Examination of Immunophenotypes in Human Cells

[Objectives]This study was conducted to establish a method for detecting the immunophenotypes of venous blood CIK cells in healthy donors and patients with triple-negative breast cancer or lung cancer by flow cytometry,and to further analyze and discuss the proportion of cellular immunophenotypes such as CD3^(+),CD4^(+),CD8^(+),CD3^(+)CD8^(+),CD3^(+)CD56^(+)in CIK cells.[Methods]Human venous blood was drawn,then anticoagulated with heparin and isolated with lymphocyte isolation solution,and the relevant immunophenotypes were detected by flow cytometry after 21 d of culture.[Results]The expression of CD3^(+)CD8^(+)and CD3^(+)CD56^(+)in the venous blood CIK cells was significantly higher in healthy donors than that in triple-negative breast and lung cancer patients.[Conclusions]CD3^(+)CD8^(+)and CD3^(+)CD56^(+)CIK cells have high anti-tumor activity.

CD200 Attenuates Methamphetamine-induced Microglial Activation and Dopamine Depletion

This study examined the neuroprotective effect of cluster of differentiation molecule 200 （CD200） against methamphetamine （METH）-induced neurotoxicity. In the in vitro experiment, neuron-microglia cultures were treated with METH （20 μmol/L）, METH （20 μmol/L）＋CD200-Fc （10 μg/mL） or CD200-Fc （10 μg/mL）. Those untreated served as control. Microglia activation expressed as the ratio of MHC-Ⅱ/CD11b was assessed by flow cytometry. The cytokines （IL-1β, TNF-α） secreted by activated microglia were detected by enzyme-linked immunosorbent assay （ELISA）. In the in vivo experiment, 40 SD rats were divided into control, METH, METH＋CD200-Fc and CD200-Fc groups at random. Rats were intraperitoneally injected with METH （15 mg/kg 8 times at 12 h interval） in METH group, with METH （administered as the same dose and time as the METH group） and CD200-Fc （1 mg/kg at day 0, 2, 4 after METH injection） in METH＋CD200-Fc group, with CD200-Fc （1 mg/kg injected as the same time as the METH＋CD200-Fc group） or with physiological saline solution in the control group. The level of striatal dopamine （DA） in rats was measured by high-performance liquid chromatography （HPLC）. The microglial cells were immunohistochemically detected for the expression of Iba-1, a marker for microglial activation. The results showed that METH could increase the microglia activation in the neuron-microglia cultures and elevate the secretion of IL-1β and TNF-α, which could be attenuated by CD200-Fc. Moreover, CD200-Fc could partially reverse the striatal DA depletion induced by METH and reduce the number of activated microglia, i.e. Iba-1-positive cells. It was concluded that CD200 may have neuroprotective effects against METH-induced neurotoxicity by inhibiting microglial activation and reversing DA depletion in striatum.

Extraction, detection, and profiling of serum biomarkers using designed Fe3O4@SiO2@HA core-shell particles

Serum biomarkers in the form of proteins （e.g. cluster of differentiation-44 （CD44）） have been demonstrated to have high clinical sensitivity and specificity for disease diagnosis and prognosis. Owing to the high sample complexity and low molecular abundance in serum, the detection and profiling of biomarkers rely on efficient extraction by materials and devices, mostly using immunoassays via antibody-antigen recognition. Antibody-free approaches are promising and need to be developed for real-case applications in serum to address the limitations of antibody-based techniques in terms of robustness, expense, and throughput. In this work, we demonstrated a novel approach using hyaluronic acid （HA）-modified materials/devices for the extraction, detection, and profiling of serum biomarkers via ligand-protein interactions. We constructed Fe304@SiOa@HA particles with different sizes through layer-by-layer assembly and for the first time applied HA-functionalized particles in the facile extraction and sequence identification of CD44 in serum by mass spectrometry. We also first validated HA-CD44 binding through electrochemical sensing using HA- modified electrodes in both standard solutions and diluted serum samples, achieving a detection limit of -0.6 ng/mL and a linear response range from I ng/mL to 10 ~tg/mL. Furthermore, we performed profiling of HA-binding serum proteome, providing a new preliminary benchmark for the construction of future databases, and we investigated selected surface chemistries of particles for the capture of proteins in serum. Our work not only resulted in the development of a platform technology for CD44 extraction/detection and HA-binding proteome identification, but also guided the design of ligand affinity-based approaches for antibody-free analysis of serum biomarkers towards diagnostic applications.

Synchrotron Radiation X-Ray Inducing a Significant Increase in the CD38 Level of Rodent Testes by Generating Oxidative Stress

Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indicated critical roles of cluster of differentiation 38(CD38) in various cellular functions and cell survival, in this study we used rodent testes as a model to determine the effects of SR X-ray irradiation on the CD38 level of the testes. We found that SR X-ray irradiation led to a significant increase in the CD38 level of rodent testes one day after the irradiation. In contrast, the SR X-ray irradiation did not produce a significant increase in the CD38 level of the testes from the rats that were administered with the antioxidant N-acetyl cysteine, thus suggesting that oxidative stress plays a significant role in the SR X-ray irradiation-induced increase in the CD38 levels. Our study has also provided evidence suggesting that poly(ADP-ribose) polymerase(PARP) activity is not involved in the SR X-ray irradiation-produced effect on the CD38 levels. Collectively, this study has provided first in vivo evidence indicating that CD38 levels can be increased by ionizing radiation, in which oxidative stress plays an important role. Because oxidative stress occurs in ionizing radiation as well as such diseases as cerebral ischemia and Parkinson's disease, oxidative stress may produce pathological effects by inducing increased CD38 levels.

LncRNA AFAP1-AS1/miR-27b-3p/VEGF-C axis modulates stemness characteristics in cervical cancer cells

Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer-promoting roles in cancer stem cells.However,the regulatory mechanism of AFAP1-AS1 in cervical cancer(CC)stem cells is unknown.The present study aimed to provide a new therapeutic target for the clinical treatment of CC.Methods:Hyaluronic acid receptor cluster of differentiation 44 variant exon 6(CD44v6)(+)CC cells were isolated by flow cytometry(FCM).Small interfering RNAs of AFAP1-AS1(siAFAP1-AS1)were transfected into the(CD44v6)(+)cells.The levels of AFAP1-AS1 were measured by quantitative real-time PCR(qRT-PCR).Sphere formation assay,cell cycle analysis,and Western blotting were used to detect the effect of siAFAP1-AS1.RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor(VEGF)-C.Results:CD44v6(+)CCcells had remarkable stemness and a high level ofAFAP1-AS1.However,AFAP1-AS1knockdownwithsiAFAP1-AS1suppressed the cell cycle transitionofG(1)/S phase and inhibited self-renewal ofCD44v6(+)CCcells,the levels of the stemnessmarkers octamer-binding transcription factor 4(OCT4),osteopontin(OPN),and cluster of differentiation 133(CD133),and the epithelialmesenchymal transition(EMT)-related proteins Twist1,matrix metalloprotease(MMP)-9,and VEGF-C.In the mechanism study,miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+)CC cells.Conclusions:LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.