Search

OBJECTIVE To investigate standard modifiable cardiovascular risk factors (SMuRFs) and prognosis of patients with acute coronary syndrome (ACS) aged 50 years or younger. STUDY DESIGN An observational study. PLACE AND DURATION OF STUDY Eleven general hospitals in Chengdu, Sichuan Province, China, from January 2017 to June 2019. METHODOLOGY Patients with ACS were stratified into younger group (≤50 years) and older group (>50 years). The baseline characteristics and prognosis were compared for two groups. Survival analysis was used to assess the long-term prognosis. RESULTS Among a total of 1982 ACS patients, 322 (16.2%) were of ≤50 years. Compared with older patients, younger patients were more likely to have at least one SMuRFs (90.0% vs. 84.3%, p=0.013). The younger group had a higher prevalence of smoking (62.8% vs. 34.1%, p

Lingyao Qi, Hanxiong Liu, Lianchao Cheng, Caiyan Cui, Xu Chen, Siqi Yang, Lin Cai Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lin CaiDepartment of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaTel/Fax +86 28-67575956Email clin63@hotmail.comPurpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to < 90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis < 0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.Keywords: renal insufficiency, acute coronary syndrome, long-term prognosis, retrospective study

Background. This study aimed to explore the mechanisms of action of the PSORI-CM01 and Yinxieling formulas in the treatment of patients with psoriasis vulgaris by analyzing gene expression in peripheral blood mononuclear cells (PBMCs). Methods. PBMC samples were collected from 21 patients before and after treatment. The study included nine patients in the PSORI-CM01 treatment group, 12 patients in the Yinxieling treatment group, and nine patients in the healthy control group. Gene expression levels in PBMCs were determined using the Affymetrix gene chip technology. Results. In the PSORI-CM01 group before and after treatment, a total of 668 differentially expressed genes were found, of which 445 were upregulated and 223 were downregulated. Before and after Yinxieling treatment, 657 differentially expressed genes were found, of which 168 were upregulated and 489 were downregulated. Venn analysis showed that 78 genes were not differentially expressed in the PSORI-CM01 group and 74 were not differentially expressed in the Yinxieling group compared with those in the controls. Among these genes, 72 genes were common to both groups, which were the genes on which the two drugs acted jointly. The results of KEGG analysis and Venn analysis on the signalling pathways of drug action in treatment groups showed that haemostasis and pathways involving Rho GTPases were common signalling pathways of drug action in the two groups. Conclusions. By a comparative analysis of the treatment groups, we found that both drugs have a positive effect on patients with psoriasis vulgaris, primarily by regulating the pathways related to platelet activation, aggregation, and blood coagulation. Trial registration: ChiCTR, ChiCTR-TRC-14005185, Registered 8 August 2014, http://www.chictr.org.cn/showproj.aspx?proj=4390

Aims/Introduction The predictive value of admission hyperglycemia in the long‐term prognosis of acute myocardial infarction patients is still controversial. We aimed to investigate this value based on the diabetes status. Materials and Methods We carried out a multicenter, retrospective study of 1,288 acute myocardial infarction patients enrolled in 11 hospitals between March 2014 and June 2019 in Chengdu, China. The patients were classified into those with diabetes and those without diabetes, each was further divided into: hyperglycemia and non‐hyperglycemia subgroups, according to the optimal cut‐off value of the blood glucose to predict all‐cause mortality during follow up. The end‐points were all‐cause death and major adverse cardiovascular and cerebrovascular events, including all‐cause death, non‐fatal myocardial infarction, vessel revascularization and non‐fatal stroke. Results In the follow‐up period of 15 months, we observed 210 (16.3%), 6 (0.5%), 57 (4.4%) and 34 (2.6%) cases of death, non‐fatal myocardial infarction, revascularization and non‐fatal stroke, respectively. The optimal cut‐off values of admission blood glucose for patients with diabetes and patients without diabetes to predict all‐cause mortality during follow up were 14.80 and 6.77 mmol/L, respectively. We divided patients with diabetes (n = 331) into hyperglycemia (n = 92) and non‐hyperglycemia (n = 239), and patients without diabetes (n = 897) into hyperglycemia (n = 425) and non‐hyperglycemia (n = 472). The cumulative rates of all‐cause death and major adverse cardiovascular and cerebrovascular events among the patients in each hyperglycemia group was higher than that in the corresponding non‐hyperglycemia group (P, The prognostic value of admission hyperglycemia on long‐term prognosis remains elusive, especially in acute myocardial infarction patients with diabetes. Regarding acute myocardial infarction patients, there has been no accurate threshold of admission hyperglycemia to predict mortality. Therefore, in our study, we used different cut‐off values in patients with and without diabetes to discuss their predictive value in the long‐term prognosis of acute myocardial infarction patients.

Background: laparoscopic or open cortical-sparing adrenalectomy (LCSA or OCSA; CSA) for treatment of bilateral pheochromocytomas (bPHEO) in multiple endocrine neoplasia type 2 (MEN2) offers a postoperative corticosteroid independence and is balanced against the risk of local recurrence. In this study, the optimal surgical approach and the value of the simultaneous bilateral LCSA/OCSA (SB-LCSA/ SB-OCSA) were further assessed.Methods: A total of 31 patients (54.8% women) were diagnosed with bPHEO in MEN2 at a median age at initial presentation of 38 years (range, 23–78). Twenty- seven patients (87.1%) presented with synchronous. With the exception two patients respectively presenting MEN2A died of MTC metastasis or MEN2B declined surgery, each of other 29 underwent initial CSA, and in 23 (79.3%), of whom 18 had SB-LCSA and 5 had SB-OCSA duration of the same anesthesia (synchronous surgery); whereas metachronous CSA was in 6 (20.7%), including 1 had metachronous bilateral LCSA, 2 had metachronous bilateral OCSA (metachronous surgery) and 3 had LCSA/OCSA (hybrid) surgery.Results: All 31 patients associated with RET-C634 mutations, as MEN2A (90.3%) and RET-M918T, as MEN2B (9.7%), respectively. No conversion and intraoperative or postoperative severe complications were necessary. There were less bleeding volume, and shorter hospitalizations between in SB-LCSA compared with those in SB-OCSA, as well as synchronous surgery versus metachronous (hybrid) surgery (all P < 0.05). An initial bilateral postoperative corticosteroid replacement was necessary in 14 patients (45.2%). During a median follow-up period of 7 years (range, 1.8–23), 3 of these patients (10.3%) showed a persistent/recurrent disease and needed reoperation.Conclusions: CSA for bPHEO in MEN2 has a relatively low recurrence and avoids lifelong corticosteroid replacement in well over half the patients. SB-LCSA for treatment of these synchronous bPHEO is safe and feasible, should be recommended as a prioritized surgical approach of choice.

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease. An induced pluripotent stem cell line (EHTJUi003-A) was generated from umbilical cord blood mononuclear cells (UCBMCs) of a female neonate with heterozygous mutation of p.L460Wfs (c.1377delC) in the MYBPC3 gene. This iPSC model offers a very valuable resource to study the pathological mechanism of HCM in vitro.

Familial Arrhythmogenic Right Ventricular Dysplasia (ARVD) is a primary cardiomyopathy characterized by the abnormality of the right ventricular muscle. ARVD may be life-threatening due to the induction of paroxysmal refractory ventricular tachycardia or supraventricular arrhythmia. A human induced pluripotent stem cell line (EHTJUi004-A) was generated from human umbilical cord blood mononuclear cells (UCBMCs) of a female neonate with heterozygous mutation of p.Leu1563fs (c.4683_4684delCT) in the DSP gene. This iPS cell line resource provides an ideal in vitro model to study the pathological mechanism of ARVD.

Ferroptosis is a newly described regulated form of cell death that contributes to the progression of non-small cell lung cancers (NSCLCs). MicroRNA-302a-3p (miR-302a-3p) plays critical roles in the tumorigenicity of different cancers; however, its function and underlying mechanism in ferroptosis and NSCLCs remain unclear. Human NSCLCs cells were incubated with miR-302a-3pmimic or inhibitor in the presence or absence of erastin or RSL3. Cell viability, colony numbers, lactate dehydrogenase (LDH) releases, lipid peroxidation and intracellular iron level were measured. Besides, the synergistic effects of cisplatin and paclitaxel with miR-302a-3p were determined. miR-302a-3p level was reduced in human NSCLCs cells and tissues. ThemiR-302a-3p mimic induced lipid peroxidation, iron overload and ferroptosis, thereby inhibiting cell growth and colony formation of NSCLCs cells. Conversely, the miR-302a-3p inhibitor block ederastin- or RSL3-related ferroptosis and tumor suppression. Additionally, we found that miR-302a-3p directly bound to the 3���-untranslational region of ferroportin to decrease its protein expression, and that ferroportin overexpression significantly prevented miR-302a-3p mimic-induced ferroptosis and tumor inhibition. Moreover, the miR-302a-3p mimic sensitized NSCLCs cells to cisplatin and paclitaxel chemotherapy. miR-302a-3p functions as a tumor inhibitor, at least partly, via targeting ferroportin to induce ferroptosis of NSCLCs.

Since the outbreak of COVID-19 corona virus in late 2019, it has become a tremendous threat to the whole world. Driven by the mission to save lives, we develop a fever screening and tracing system which can detect patients with fever symptom, and identify the patients using face recognition. In addition, our big data AI platform enables the tracing of the patients possible. A real-time alert sent to the personnel on duty on a web or mobile app activates the action to trace the patient and the close contacts providing an effective means to control the spread of the virus.

Spinal cord injury (SCI) is a devastating medical condition with profound social and economic impacts. Although research is ongoing, current treatment options are limited and do little to restore functionality. However, recent studies suggest that mesenchymal stem cell-derived exosomes (MSC-exosomes) may hold the key to exciting new treatment options for SCI patients. MSCs are self-renewing multipotent stem cells with multi-directional differentiation and can secrete a large number of exosomes (vesicles secreted into the extracellular environment through endocytosis, called MSC-exosomes). These MSC-exosomes play a critical role in repairing SCI through promoting angiogenesis and axonal growth, regulating inflammation and the immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be utilized to transport genetic material or drugs to target cells, and their relatively small size makes them able to permeate the blood-brain barrier. In this review, we summarize recent advances in MSC-exosome themed SCI treatments and cell-free therapies to better understand this newly emerging methodology.

Background. A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods. The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results. QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001 ). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05 ), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05 ). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan–Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004 ) and overall survival (OS) times ( P = 0.010 ) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004 ) and OS times ( P = 0.014 ) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

Background: Traditional Chinese medicines (TCMs) have been used to manage psoriasis since thousands of years and are associated with advantages such as long remission period and few side effects. PSORI-CM01 is a clinical TCM formula for treating the blood stasis syndrome of psoriasis vulgaris. It is optimised from Yin Xie Ling, a herbal preparation formulated by the Chinese national medical master Xuan Guowei. In the present study, we used microRNA (miRNA) chip technology to analyse the effects of PSORI-CM01 and Yin Xie Ling on miRNA differential expression in the peripheral blood monocytes of patients with blood stasis syndrome of psoriasis vulgaris.Methods: Blood samples collected from healthy subjects and patients with blood stasis syndrome of psoriasis vulgaris were obtained from the Department of Dermatology in the Guangdong Provincial Hospital of Chinese Medicine. These samples were obtained before and after treatment with PSORI-CM01 or Yin Xie Ling. Differentially expressed miRNAs were analysed by performing miRNA expression microarray to evaluate the mechanisms underlying the effects of the two formulations.Results: It was found that hsa-miR-3184-3p, hsa-miR-3653-3p, hsa-miR-20a-3p, hsa-miR-5681b, and hsa-miR-26a-5p were differentially expressed between the PSORI-CM01 and healthy control groups as well as between the Yin Xie Ling and healthy control groups before treatment, without any significant differences in their expression after treatment. The results revealed that the therapeutic effect of PSORI-CM01 on psoriasis was mediated mainly via the regulation of the adherens junction, thyroid hormone signalling, and proteoglycans in cancer pathways, whereas that of Yin Xie Ling was mediated mainly via the regulation of the endoplasmic reticulum protein processing, Hippo signalling, adherens junction, thyroid hormone signalling, cell cycle, proteoglycans in cancer, p53 signalling, oocyte meiosis, and unsaturated fatty acid biosynthesis pathways.Conclusions: The findings demonstrate that PSORI-CM01 and Yin Xie Ling are beneficial for treating blood stasis syndrome of psoriasis vulgaris through the regulation of hsa-miR-20a-3p and hsa-miR-3184-3p expression and, consequently, through the adherens junction, thyroid hormone signalling, and proteoglycans in cancer pathways.Trial registration: Registration number, ChiCTR-TRC-14005185; Date of registration, 8 August 2014.

Background The association of central venous pressure (CVP) and mortality and acute kidney injury (AKI) in critically ill adult patients remains unclear. We performed a meta-analysis to determine whether elevated CVP is associated with increased mortality and AKI in critically ill adult patients. Methods We searched PubMed and Embase through June 2019 to identify studies that investigated the association between CVP and mortality and/or AKI in critically ill adult patients admitted into the intensive care unit. We calculated the summary odds ratio (OR) and 95% CI using a random-effects model. Results Fifteen cohort studies with a broad spectrum of critically ill patients (mainly sepsis) were included. On a dichotomous scale, elevated CVP was associated with an increased risk of mortality (3 studies; 969 participants; OR, 1.65; 95% CI, 1.19–2.29) and AKI (2 studies; 689 participants; OR, 2.09; 95% CI, 1.39–3.14). On a continuous scale, higher CVP was associated with greater risk of mortality (5 studies; 7837 participants; OR, 1.10; 95% CI, 1.03–1.17) and AKI (6 studies; 5446 participants; OR, 1.14; 95% CI, 1.06–1.23). Furthermore, per 1 mmHg increase in CVP increased the odds of AKI by 6% (4 studies; 5150 participants; OR, 1.06; 95% CI, 1.01–1.12). Further analyses restricted to patients with sepsis showed consistent results. Conclusions Elevated CVP is associated with an increased risk of mortality and AKI in critically ill adult patients admitted into the intensive care unit. Trial registration PROSPERO, CRD42019126381

Background To analyze the expression of miRNA (microRNA) in peripheral blood mononuclear cells in patients with Psoriasis vulgaris with different TCM syndromes by miRNA chip. It further revealed the micromaterial basis of different syndrome types of psoriasis at the miRNA level. Methods Peripheral blood monocytes were collected and prepared from 30 patients with Psoriasis vulgaris (including 9 patients of blood heat syndrome, 8 patients of blood stasis syndrome, and 13 patients of blood dry syndrome) and 9 healthy controls. The miRNA expression profile of peripheral blood monocytes was detected by Agilent Hum miRNA chip. Results Compared to the healthy control group, 156 upregulated and 242 downregulated miRNAs were detected in all psoriasis patients. Compared to the healthy control group, 40 miRNAs were upregulated and 44 were downregulated in the blood heat syndrome group. Furthermore, there were 49 upregulated miRNAs and 44 downregulated miRNAs in the dry syndrome group as compared to the healthy control group. Also, 67 miRNAs were upregulated and 154 miRNAs were downregulated in the blood stasis syndrome group as compared to the healthy control group. Conclusions There are common different miRNAs and pathways, as well as specific miRNAs between the psoriasis and the healthy control groups. Trial registration ChiCTR-TRC-14005185 registered on August 8, 2014.

With people's changing life style and dietary habits, the prevalence of type 2 diabetes mellitus (T2DM) has become much more serious than ever before. T2DM is a polygenic metabolic disorder, resulting from the interaction of genetic and various environmental factors. Among all the T2DM related genes, the transcription factor 7 like 2 (TCF7L2) gene is one of the most relevant risk-related genes for T2DM. However, the role of TCF7L2 in T2DM pathogenesis has not yet been interpreted thoroughly. Based on the experimental studies in recent years, this review discusses several possible mechanisms of T2DM pathogenesis induced by TCF7L2.

Quality control of processed Radix Aconiti with toxicity and clinical therapeutic efficacy is very important since it is a widely used traditional herbal medicine with both therapeutic and highly toxic activities. However, until now the existing quality control methods have only been able to assess the toxicity of the different Radix Aconiti Preparata, but could not evaluate their clinical efficacy and clarify their precise mechanism of action. In this study, a urinary metabonomic study using UPLC-Q-TOF-HDMS combined with pharmacodynamics was performed for the first time to assess the holistic efficacy and to explore the potential mechanism of the different Radix Aconiti Preparata for treating rheumatic arthritis (RA) in rats. High pressure steamed Radix Aconiti Preparata (SRAP) that was steamed for one hour and boiled Radix Aconiti Preparata (BRAP) that was boiled for six hours were selected as representatives of different Radix Aconiti preparata. As a result, both SRAP and BRAP showed good effects on treating RA from the integrated evaluation by histological results, biochemical parameters and pattern recognition analysis. Meanwhile, a metabonomic investigation was conducted to study the mechanism of the SRAP and BRAP for treating RA. Multivariate statistical analyses such as OPLS-DA were used to identify potential biomarkers in urine. As a result, fifteen potential biomarkers have been found by comparison with the model and the Radix Aconiti Preparata treatment groups. The potential biomarkers mainly affect four metabolic pathways, including phenylalanine metabolism, tryptophan metabolism, fatty acid metabolism, and arginine and proline metabolism. This work is helpful to evaluate the clinical efficacy of Radix Aconiti Preparata and clarify their precise mechanism of action for the treatment of arthritis.

Familial exudative vitreoretinopathy (FEVR) is an autosomal dominant genetic disease. An induced pluripotent stem cell line (EHTJUi002-A) was generated from umbilical cord blood mononuclear cells (UCBMCs) of a neonate with heterozygous mutation of p.W226X(c.678G>A) in the FZD4 gene. This iPSC model offers a very valuable resource to study the pathological mechanism of FEVR in vitro.

Wu-tou-tang was applied to treat rheumatoid arthritis, rheumatic arthritis, and joint pain for thousands of years. Aconiti Radix Cocta is the primary component of Wu-tou-tang, and Aconiti Radix and Pinelliae Rhizoma is one of the famous combination taboos in traditional Chinese medicine. A urinary metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to quantify the changes of the endogenous metabolites in the urine of adjuvant-induced arthritis rats treated by Wu-tou-tang and Wu-tou-tang and Pinelliae Rhizoma (WP) co-decoctions. There was a clear separation between Wu-tou-tang and WP co-decoction treated groups in the PCA model. 16 potential biomarkers had been identified which correlated with how Pinelliae Rhizoma influenced the therapeutic effect made by Wu-tou-tang. Results showed that it could reduce the therapeutic effects or make some side effects when Pinelliae Rhizoma is added in Wu-tou-tang. This is the first time to use metabonomics to investigate the reason of combination taboo.

This study focuses on the function of NSSR1, a splicing factor, in neuronal injury in the ischemic mouse brain using the transient global cerebral ischemic mouse model and the cultured cells treated with oxygen-glucose deprivation (OGD). The results showed that the cerebral ischemia triggers the expression of NSSR1 in hippocampal astrocytes, predominantly the dephosphorylated NSSR1 proteins, and the Exon3 inclusive NCAM-L1 variant and the Exon4 inclusive CREB variant. While in the hippocampus of astrocyte-specific NSSR1 conditional knockdown (cKD) mice, where cerebral ischemia no longer triggers NSSR1 expression in astrocytes, the expression of Exon3 inclusive NCAM-L1 variant and Exon4 inclusive CREB variant were no longer triggered as well. In addition, the injury of hippocampal neurons was more severe in astrocyte-specific NSSR1 cKD mice compared with in wild-type mice after brain ischemia. Of note, the culture media harvested from the astrocytes with overexpression of NSSR1 or the Exon3 inclusive NCAM-L1 variant, or Exon4 inclusive CREB variant were all able to reduce the neuronal injury induced by OGD. The results provide the evidence demonstrating that: (1) Splicing factor NSSR1 is a new factor involved in reducing ischemic injury. (2) Ischemia induces NSSR1 expression in astrocytes, not in neurons. (3) NSSR1-mediated pathway in astrocytes is required for reducing ischemic neuronal injury. (4) NCAM-L1 and CREB are probably mediators in NSSR1-mediated pathway. In conclusion, our results suggest for the first time that NSSR1 may provide a novel mechanism for reducing neuronal injury after ischemia, probably through regulation on alternative splicing of NCAM-L1 and CREB in astrocytes.

Tumor stem cells (TSCs) are considered as the “seeds” in tumor development, metastasis and recurrence. Despite the various immunosurveillance mechanisms in the host, TSCs may possess the phenotypic and functional properties to evade host immunosurveillance and immune-mediated rejection in immunologically intact individuals. The mechanisms of TSC recognition and their consequent destruction are actively disturbed by various processes, including altered immunogenicity of TSCs, production of TSC-derived regulatory molecules, and interaction of TSCs with tumor-infiltrating immune cells. In addition to these TSC-mediated mechanisms, the diverse mesenchymal cells and cytokines in the tumor microenvironment are contribute to TSC immune escape. Recent mechanistic studies provide a more comprehensive understanding of TSCs in the biology, prevention, and therapy of solid tumors. This review will focus on the latest findings for mechanisms underlying TSCs’ escape from the attack of immune system.

Neural salient serine/arginine-rich protein 1 (NSSR1) has been found to play important roles in inhibiting alternative splicing during heat shock and mitosis and is predominantly expressed in neural tissues such as cerebral neurons, cerebellar Purkinje cells and bipolar cells of the retina. Recently, NSSR1 has also been shown to be highly expressed in the testes, suggesting its potential roles in reproductive system. In this report, the expression of NSSR1 in the columnar epithelium of the endometrium and gland epithelium during the development of the mouse uterus, the regulation of NSSR1 level by testosterone in the adult mouse uterus, and expression level of NSSR1 in both human endometrial carcinomas and ovarian cancers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. We demonstrated that the expression of NSSR1 was developmentally regulated in the columnar epithelium of the endometrium and gland epithelium in the mouse uterus. Additionally, the NSSR1 level in the mouse uterus was maintained and regulated by testosterone. Interestingly, an enhanced level of NSSR1 was observed in both human endometrial carcinomas and ovarian cancers. Our results suggest that expression and distribution of NSSR1 is developmentally and hormonally regulated and up-regulated in endometrial carcinomas as well as ovarian cancers, indicating its potential involvement in uterine development and tumorgenesis.

// Weijia Liao 1,* , Weilong Liu 3,* , Xing Liu 4 , Qing Yuan 4 , Ying Ou 4 , Yao Qi 4 , Wanqiu Huang 5 , Yun Wang 4 and Jian Huang 1,2,3,4 1 Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China 2 Key Laboratory of Systems Biomedicine (Ministry of Education), Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China 3 Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People’s Hospital, Guangdong Medical College, Shenzhen, China 4 Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, China 5 Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * These authors have contributed equally to this work Correspondence to: Jian Huang, email: // Keywords : hepatocellular carcinoma ; FAM83D ; up-regulation ; overall survival; methylation Received : March 20, 2015 Accepted : May 30, 2015 Published : June 10, 2015 Abstract The identification of potential oncogenes plays an important role in finding novel therapeutic targets for many cancers, including hepatocellular carcinoma (HCC), which is one of the most common cancers worldwide. In our previous research, using microarray technology, we found that FAM83D was overexpressed in HCCs. However, whether the overexpression of FAM83D contributes to hepatocarcinogenesis remains unclear. In this study, we found that FAM83D was significantly upregulated in 76.6% (167 of 218) of the HCC specimens at the mRNA level and in 69.44% (50 of 72) of the HCC specimens at the protein level compared with adjacent non-cancerous liver specimens, as indicated by RT-PCR and immunohistochemical staining, respectively. The FAM83D mRNA expression level was positively correlated with the level of alpha-fetoprotein (AFP) ( ≥ 100 ng/ml), the clinical TNM stage, the presence of a portal vein tumor thrombus (PVTT), disease-free survival (DFS) and the overall survival (OS) time of the HCC patients ( P < 0.05). K nocking down FAM83D significantly promoted the growth of Huh7 and HepG2 cells, as demonstrated in an RNA interference assay. Moreover, the DNA methylation status of the FAM83D promoter was significantly reduced in the HCC specimens with overexpression of FAM83D gene . Our data suggest that the upregulation of FAM83D , a potential oncotarget gene, may be triggered by epigenetic events and can contribute to hepatocarcinogenesis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory and autoimmune disease accompanied by the destruction and deformities of joints. Adjuvant-induced arthritis (AIA) is one of the excellent animal models of RA used to understand disease pathogenesis and screen potential drugs. In this paper, a urinary metabonomics method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been established to investigate the disease progression of AIA and find potential biomarkers of secondary inflammation in AIA rats. 24 potential biomarkers were identified, including xanthurenic acid, kynurenic acid, 4-pyridoxic acid, and phenylalanine, which revealed that tryptophan metabolism, phenylalanine metabolism, gut microbiota metabolism and energy metabolism were disturbed in AIA rats. These potential biomarkers and their corresponding pathways are helpful to further understand the mechanisms of AIA and pathogenesis of RA. This study demonstrates that metabonomics based on UPLC-Q-TOF-MS is a powerful methodology to analyze the underlying disease pathogenesis.

The anti-HIV agent MAP30 (Momordica anti-HIV protein, 30 kDa) inhibits the proliferation of BC-2, an AIDS-related primary effusion lymphoma (PEL) cell line derived from an AIDS patient. BC-2 cells are latently infected with Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8). We examined the effect of MAP30 on the expression of viral and cellular genes in BC-2 during latent and lytic states of the viral life cycle. By Northern analysis and RT-PCR, we found that MAP30 downregulates the expression of viral cyclin D (vCD), viral interleukin-6 (vIL-6), and viral FLIP (vFLIP), genes involved in cell cycle regulation, viral pathogenesis, and apoptosis. By pathway-specific cDNA microarray analysis, we found that BC-2 cells express high levels of egr-1, ATF-2, hsp27, hsp90, IkappaB, mdm2, skp1, and IL-2, cellular genes involved in mitogenesis, tumorigenesis, and inhibition of apoptosis in NFkappaB and p53 signaling pathways. These results define for the first time the specific cellular pathways involved in AIDS-related tumorigenesis and suggest specific novel targets for the treatment. Furthermore, we found that MAP30 downregulates the expression of egr-1, ATF-2, hsp27, hsp90, IkappaB, mdm2, and Skp1, while it upregulates the pro-apoptotic-related genes Bax, CRADD, and caspase-3. Thus, MAP30 modulates the expression of both viral and cellular genes involved in KS pathogenesis. These results provide valuable insight into the molecular mechanisms of MAP30 anti-KS action and suggest its utility as a therapeutic agent against AIDS-related tumors.

After birth, the full-term ductus arteriosus actively constricts and undergoes extensive histologic changes that prevent subsequent reopening. These changes are thought to occur only if a region of intense hypoxia develops within the ductus wall after the initial active constriction. In preterm infants, indomethacin-induced constriction of the ductus is often transient and is followed by reopening. Prostaglandins and nitric oxide both play a role in inhibiting ductus closure in vitro. We hypothesized that combined inhibition of both prostaglandin and nitric oxide production (with indomethacin and N-nitro-L-arginine (L-NA), respectively) may be required to produce the degree of functional closure that is needed to cause intense hypoxia. We used preterm (0.67 gestation) newborn baboons that were mechanically ventilated for 6 d: 6 received indomethacin alone, 7 received indomethacin plus L-NA, and 16 received no treatment (control). Just before necropsy, only 25% of control ductus and 33% of indomethacin-treated ductus were closed on Doppler examination; in contrast, 100% of the indomethacin-plus-L-NA-treated ductus were closed. Control and indomethacin-treated baboons developed negligible-to-mild ductus hypoxia (EF5 technique). Similarly, there was minimal evidence of ductus remodeling. In contrast, indomethacin-plus-L-NA-treated baboons developed intense hypoxia in regions where the ductus was most constricted. The hypoxic muscle strongly expressed vascular endothelial growth factor, and proliferating luminal endothelial cells filled and occluded the lumen. In addition, cells in the most hypoxic regions were undergoing DNA fragmentation. In conclusion, preterm newborns are capable of remodeling their ductus, just like the full-term newborn, if they can reduce their luminal blood flow to a point that produces intense ductus wall hypoxia. Combined prostaglandin and nitric oxide inhibition may be necessary to produce permanent closure of the ductus and prevent reopening in preterm infants.

A urinary metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of Wu-tou decoction (WTD), a traditional Chinese medicine (TCM) formula used to treat rheumatoid arthritis (RA), in adjuvant-induced arthritis (AIA) rat model. Multivariate statistical approaches, such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were used to distinguish healthy control group, AIA model group and WTD treated group and find potential biomarkers. There was a clear separation among the three groups in PCA model. Sixteen potential biomarkers had been identified using OPLS-DA, and 11 of them was considered to be in response to therapeutic effects of WTD involved in tryptophan metabolism, phenylalanine metabolism, tricarboxylic acid (TCA) cycle, bile acid biosynthesis, steroid hormone biosynthesis and valine metabolism. In this study, WTD also showed good anti-inflammatory and antioxidant activities in vivo, and it could suppress histopathological changes of AIA rats. There might be a correlation between these results and the regulation of the disturbed metabolites in urine. This study demonstrates that metabonomics is a powerful methodology to gain insight in the mechanism of TCM formula in therapy.

Thrombin-treated tumor cells induce a metastatic phenotype in experimental pulmonary murine metastasis. Thrombin binds to a unique protease-activated receptor (PAR-1) that requires N-terminal proteolytic cleavage for activation by its tethered end. A 14-mer thrombin receptor activation peptide (TRAP) of the tethered end induces the same cellular changes as thrombin. Four murine tumor cells (Lewis lung, CT26 colon CA, B16F10 melanoma, and CCL163 fibroblasts) contain PAR-1, as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). B16F10 cells did not contain the two other thrombin receptors, PAR-3 and glycoprotein Ib. TRAP-treated B16F10 tumor cells enhance pulmonary metastasis 41- to 48-fold (n = 17). Thrombin-treated B16F10 cells transfected with full-length murine PAR-1 sense cDNA (S6, S7, S14, and S22) enhanced their adhesion to fibronectin 1.5- to 2.4-fold (n = 5, P < .04), whereas thrombin-treated wild-type cells do not. S6 (adhesion index, 1.5-fold) and S14 (index, 2.4-fold) when examined by RT-PCR and Northern analysis showed minimal expression of PAR-1 for S6 over wild-type and considerable expression for S14. Immunohistochemistry showed greater expression of PAR-1 for S14 compared with wild-type or empty-plasmid transfected cells. In vivo experiments with the thrombin-treated S14 transfectant showed a fivefold to sixfold increase in metastases compared with empty-plasmid transfected thrombin-treated naive cells or S6 cells (n = 20, P = .0001 to .02). Antisense had no effect on thrombin-stimulated tumor mass. Thus, PAR-1 ligation and expression enhances and regulates tumor metastasis.

Thrombin-treated tumor cells induce a metastatic phenotype in experimental pulmonary murine metastasis. Thrombin binds to a unique protease-activated receptor (PAR-1) that requires N-terminal proteolytic cleavage for activation by its tethered end. A 14-mer thrombin receptor activation peptide (TRAP) of the tethered end induces the same cellular changes as thrombin. Four murine tumor cells (Lewis lung, CT26 colon CA, B16F10 melanoma, and CCL163 fibroblasts) contain PAR-1, as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). B16F10 cells did not contain the two other thrombin receptors, PAR-3 and glycoprotein Ib. TRAP-treated B16F10 tumor cells enhance pulmonary metastasis 41- to 48-fold (n = 17). Thrombin-treated B16F10 cells transfected with full-length murine PAR-1 sense cDNA (S6, S7, S14, and S22) enhanced their adhesion to fibronectin 1.5- to 2.4-fold (n = 5, P < .04), whereas thrombin-treated wild-type cells do not. S6 (adhesion index, 1.5-fold) and S14 (index, 2.4-fold) when examined by RT-PCR and Northern analysis showed minimal expression of PAR-1 for S6 over wild-type and considerable expression for S14. Immunohistochemistry showed greater expression of PAR-1 for S14 compared with wild-type or empty-plasmid transfected cells. In vivo experiments with the thrombin-treated S14 transfectant showed a fivefold to sixfold increase in metastases compared with empty-plasmid transfected thrombin-treated naive cells or S6 cells (n = 20, P = .0001 to .02). Antisense had no effect on thrombin-stimulated tumor mass. Thus, PAR-1 ligation and expression enhances and regulates tumor metastasis.

The overall survival for advanced head and neck squamous cell carcinoma is poor and has not changed in over 20 years. A non- replicating p53-expressing adenovirus in combination with radiation has shown promising results for this disease and is the first approved gene therapy modality worldwide. An oncolytic virus (ONYX-015) in combination with chemotherapy has also shown encouraging results. Therefore, the application of a replicating p53-expressing virus in combination with chemotherapy may be a rational advancement of this strategy. However, the adenoviral E1b-19kD protein is a potent inhibitor of apoptosis and may compromise the therapeutic efficacy of a p53-expressing oncolytic virus, inhibiting the apoptotic effect of both p53 and chemotherapy. We hypothesized that an E1b-19kD gene deletion together with p53 expression in combination with chemotherapy could further improve the ability of a replicating adenoviral vector to kill head and neck cancer cells. In two head and neck cancer cell lines (1586 and SCC15), a p53-expressing E1b-19kD-deleted replicating virus (Adp53dl19k) increased the amount of apoptosis by more than three-fold compared to a replicating control virus (Ad-co), and almost two-fold compared to a E1b-19kD-deleted virus that does not express p53 (Ad-dl19k). In the presence of cisplatin, at a dose that does not induce apoptosis in these cells, the apoptotic effect of Adp53dl19k was almost doubled, whereas Ad-co induced only minimal apoptosis. In the same two head and neck cancer cell lines, infection with Adp53dl19k in combination with cisplatin also resulted in reduced cell viability, as compared to Ad- co or a p53-expressing but not E1b-19k-deleted virus (Adp53). In conclusion, a non-cytotoxic dose of chemotherapy can markedly enhance the induction of apoptosis and cancer cell death induced by a replicating p53-expressing virus, but only in the presence of an E1b-19kD deletion.

The association between a new human herpesvirus-like agent and various forms of Kaposi's sarcoma was examined by PCR. The DNA sequences of this agent were detected in 7 of 8 classic Kaposi's sarcoma specimens, 12 of 12 AIDS-associated specimens from the United States, and 7 of 10 specimens from African endemic Kaposi's sarcoma. Polymorphism of the herpesvirus-like DNA in the Kaposi's tissue from different populations was observed by both single-strand conformational polymorphism and direct sequencing. Furthermore, the presence and expression of the virus was detected in some Kaposi's tumours by Southern and northern blotting. This herpesvirus may be involved in the pathogenesis of different kinds of Kaposi's sarcoma seen among distinct and unrelated populations.

Since trisomy 12 is the most common chromosome abnormality found in CLL and MDM2 has been mapped to this chromosome, we examined the possible association of MDM2 in the pathogenesis of CLL. A rearrangement of the MDM2 gene was observed in 4 of 11 peripheral blood mononuclear cells (PBMC) from patients with CLL by Southern blot hybridization. Expression of MDM2 was detected in all of the CLL samples examined by Northern blot. However, neither gross amplification nor overexpression of the MDM2 gene was found in CLL. The data suggest that MDM2 may play a role in the pathogenesis of CLL and may help to explain how abnormalities of chromosome 12 are related to CLL.

Recently, DNA sequences of what appear to be a unique human herpesvirus-like agent (HHV-8) have been detected in different types of Kaposi's sarcoma (KS) tumors (Chang, Y., E.C. Cesarman, M.S. Pessin, F. Lee, J.C. Culpepper, D.M. Knowles, and P.S. Moore. 1994. Science (Wash. DC). 266:1865-1869). To further elucidate the possibility that HHV-8 plays a role in the pathogenesis of KS, the expression of HHV-8 RNA was examined in fresh KS tissue specimens which were found to harbor HHV-8 DNA by polymerase chain reaction (PCR). The transcription of HHV-8 RNA was detected by RT-PCR in 26 of 29 specimens (89.7%) of the KS tumors including 2 of 3 CKS and 24 of 26 AIDS-KS. No positive signal was detected in eight biopsy specimens of normal skin from healthy donors. By Northern blot analysis, the expression of HHV-8 was detected in 2 of 10 KS tumors examined. Furthermore, the RNA transcripts were observed in endothelial cells lining the irregular vascular spaces and perivascular spindle-shaped cells histologically characteristic of KS in 2 out of 8 different KS specimens examined by in situ hybridization using an antisense probe specific of HHV-8. The detection of RNA expression of HHV-8 in KS tumors further supports the possible etiopathogenic role of this virus in the development of KS.

BACKGROUND: The hygiene hypothesis suggests that helminth infections prevent a range of autoimmune diseases. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the effects of S. japonicum infection on collagen-induced arthritis (CIA), male DBA/1 mice were challenged with unisexual or bisexual S. japonicum cercariae two weeks prior to bovine type II collagen (CII) immunization or at the onset of CIA. S. japonicum infection prior to CII immunization significantly reduced the severity of CIA. ELISA (enzyme linked immunosorbent assay) showed that the levels of anti-CII IgG and IgG2a were reduced in prior schistosome-infected mice, while anti-CII IgG1 was elevated. Splenocyte proliferation against both polyclonal and antigen-specific stimuli was reduced by prior schistosome infection as measured by tritiated thymidine incorporation ((3)H-TdR). Cytokine profiles and CD4(+) T cells subpopulation analysis by ELISA and flow cytometry (FCM) demonstrated that prior schistosome infection resulted in a significant down-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β and IL-6) and Th1 cells, together with up-regulation of the anti-inflammatory cytokine IL-10 and Th2 cells. Interestingly, the expansion of Treg cells and the reduction of Th17 cells were only observed in bisexually infected mice. In addition, prior schistosome infection notably reduced the expression of pro-inflammatory cytokines and receptor activator of NF-κB ligand (RANKL) in the inflamed joint. However, the disease was exacerbated at one week after infection when established CIA mice were challenged with bisexual cercariae. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence that the Th2 response evoked by prior S. japonicum infection can suppress the Th1 response and pro-inflammatory mediator and that bisexual infection with egg-laying up-regulates the Treg response and down-regulates the Th17 response, resulting in an amelioration of autoimmune arthritis. The beneficial effects might depend on the establishment of a Th2-dominant response rather than the presence of the eggs. Our results suggest that anti-inflammatory molecules from the parasite could treat autoimmune diseases.

OBJECTIVES HIV-1 transcripts have been detected in AIDS-related Kaposi's sarcoma (KS) tissues within the factor XIIIa + dermal dendrocytes present in the tumor. Various cytokines and growth factors have been shown to influence the growth of KS-derived cells in vitro. HIV-1 preferentially infects CD4+ cells and has also been found to infect some CD4- cells in vitro. The susceptibility of cultured KS cells in vitro to infection with HIV-1 and the expression of interleukin (IL)-1 beta, IL-6 and basic fibroblast growth factor (bFGF) after exposure to HIV-1 was examined. METHODS The susceptibility of two different KS-derived cell cultures to HIV-1 infection was examined by the expression of p24 antigen, detection of proviral sequence and electron microscopy. The expression of IL-1 beta, IL-6 and bFGF was detected by enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. RESULTS KS-derived cells can be infected by HIV-1 in vitro. Both KS-derived cells were found to express CD4 mRNA. The expression of IL-1 beta and IL-6 was increased, whereas the expression of bFGF was not stimulated after exposure of KS cells to HIV-1. CONCLUSION These experiments describe the in vitro infection of KS-derived cells by HIV-1 and the expression of various cytokines and growth factor following infection. The increased production of cytokines observed following such infection may be involved in the pathogenesis of AIDS-related KS.

Fibroblast growth factors (FGFs), such as basic FGF, have been implicated in the growth of Kaposi's sarcoma (KS) cells in vitro. In the evaluation of the expression of the various genes of the different members of the FGF family and their receptors in fresh KS tissue specimens, int-2 was found to be expressed in more than half of the KS tumors examined. Using reverse transcription PCR, the expression of int-2 was detected in 21 of 38 (55.2%) fresh KS biopsy specimens. In contrast, int-2 mRNA transcripts were not found in normal appearing skin from the same patients except in one sample which was obtained from an AIDS patient with disseminated KS lesions. Sequence data confirmed that the amplified sequences were derived from int-2 mRNA with proper splicing. In addition, 12 nucleic acid alterations were identified in eight out of nine KS tumor samples sequenced. Using immunohistochemical methods, int-2 protein was detected in some of the spindle-shaped tumor cells surrounding the abnormal endothelial-lined vascular slits histologically characteristic of KS. Int-2 specific immunostaining was shown to be present in both the nuclei and cytoplasm of these spindle cells but was more pronounced in the nuclei. Neither amplification nor gross rearrangement of the int-2 gene was detected in KS lesions by Southern blot analysis. These results suggest that the expression of int-2 may play a role in the pathogenesis KS by stimulating local angiogenesis and cell proliferation.

OBJECTIVE Tat, an essential regulatory protein of HIV, acts as a growth factor for Kaposi's sarcoma (KS)-derived cells in culture. We tested the hypothesis that HIV-negative epidemic KS patients who are also at high risk for HIV disease might have been infected with a defective HIV-1 virus that retained the ability to express Tat. METHODS We evaluated the presence of Tat sequences in KS tissue and peripheral blood mononuclear cells (PBMC) of HIV-1-negative individuals with epidemic KS who had risk factors for HIV infection by polymerase chain reaction using specific primers for the Tat region of HIV-1. RESULTS No evidence for the presence of Tat-1 sequences or for Tat-expressing defective HIV-1 virus was found. CONCLUSION These results suggest that HIV-1 Tat does not play a role in the initiation of KS in HIV-1-negative individuals. Tat might play an indirect role in epidemic KS in HIV-infected patients.

The recently discovered human herpes virus 8 (Kaposi's sarcoma-associated herpes virus) has been implicated in the pathogenesis of Kaposi's sarcoma. Using polymerase chain reaction we detected DNA sequences of this herpes virus in 11 of 14 biopsy specimens from Kaposi's sarcoma in Norwegian patients, including the immunosuppressive therapy-related type (3 of 3), the HIV-related type (4 of 5), and the classical type (4 of 6). The results support the hypothesis of a role for human herpes virus 8 in all types of Kaposi's sarcoma independent of geographical area.

Background and Design: Historically, the Kaposi's sarcoma (KS) tumor cell was generally thought to be derived from endothelial cells. However, by immunohistochemical staining of lesions, many spindle-shaped cells in KS express factor XIIIa, suggesting that they may be related to dermal dendrocytes, a perivascular cell of monocyte/ macrophage lineage. To extend our observations on tissue sections of lesions, four different established KS-derived cell lines before and after cytokine exposure, as well as biopsy specimens of KS lesions, were studied for the expression of endothelial cell and monocyte/macrophage antigens. Results: Multipassaged KS tumor cells grew predominantly as spindle-shaped cells. By immunohistochemical staining, all four KS-derived cell cultures were factor XIIIa and intercellular adhesion molecule 1 positive. Three KS-derived cell cultures were CD14 and vascular cell adhesion molecule 1 positive. Expression of factor XIIIa was upregulated by interferon gamma. By polymerase chain reaction (PCR) analysis, expression of CD4 mRNA was also detected in all four KS-derived cell cultures. Expression of these monocyte/ macrophage markers (factor XIIIa, CD14, and vascular cell adhesion molecule 1) on KS in vitro was also detected on spindle cells of KS lesions in vivo. Endothelial leukocyte adhesion molecule 1 and factor VIII expression was not detected on KS-derived cells in vitro before or after exposure to interferon gamma or tumor necrosis factor alpha. While cultured KS cells strongly expressed smooth-muscle α-actin, no detection was observed on spindle-shaped cells in vivo. Conversely, while cultured KS cells were devoid of CD34, the tissue biopsy specimens contain strongly positive spindle-shaped cells. Our results demonstrate that while KS cell lines express one antigen shared by endothelial cells, ie, vascular cell adhesion molecule 1, they lack several other endothelial cell markers such as factor VIII and endothelial leukocyte adhesion molecule 1, either before or after cytokine activation. Conclusions: Kaposi's sarcoma cell lines express several antigens linking them to dermal dendrocytes such as factor XIIIa, CD4, and CD14. ( Arch Dermatol. 1993;129:1291-1296)