Targeting ROS in cancer: rationale and strategies.

Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives.

Novel developments in the study of estrogen in the pathogenesis and therapeutic intervention of lymphangioleiomyomatosis.

OBJECTIVE: This study aimed to enhance the understanding of the role of estrogen in lymphangioleiomyomatosis(LAM) and to conclude the impact of estrogen-altering events on the condition and recent advances in estrogen-based treatments for LAM. RESULTS: LAM development is strongly linked to mutations in the tuberous sclerosis gene (TSC1/2) and the presence of estrogen. Estrogen plays a significant role in the spread of TSC2-deficient uterine leiomyoma cells to the lungs and the production of pulmonary LAM. Menstruation, pregnancy, estrogen medication, and other events that cause an increase in estrogen levels can trigger the disorder, leading to a sudden worsening of symptoms. Current findings do not support using estrogen-blocking therapy regimens. However, Faslodex, which is an estrogen receptor antagonist, presents new possibilities for future therapeutic approaches in LAM. CONCLUSION: Estrogen is crucial in the development and spread of LAM. The use of estrogen inhibitors or estrogen receptor antagonists alone does not provide good control of the disease or even poses a greater risk, and the use of a combination of mTOR receptor inhibitors, complete estrogen receptor antagonists, estrogen inhibitors, and autophagy inhibitors targeting important signaling pathways in LAM pathogenesis may be of greater benefit to the patient.

The Comparison between Cemented and Uncemented Hemiarthroplasty in Patients with Femoral Neck Fractures: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Hemiarthroplasty is the standard treatment for patients with femoral neck fractures (FNFs). Controversy exists over the use of bone cement in hip fractures treated with hemiarthroplasty. OBJECTIVE: We performed an updated systematic review and meta-analysis to compare cemented and uncemented hemiarthroplasty in patients with femoral neck fractures. METHODS: A literature review was conducted using Cochrane Library, ScienceDirect, PubMed, Embase, Medline, Web of Science, CNKI, VIP, Wang Fang, and Sino Med databases. Studies comparing cemented with uncemented hemiarthroplasty for FNFs in elderly patients up to June 2022 were included. Data were extracted, meta-analyzed, and pooled as risk ratios (RRs) and weighted mean differences (WMDs) with a 95% confidence interval (95% CI). RESULTS: Twenty-four RCTs involving 3471 patients (1749 cement; 1722 uncemented) were analyzed. Patients with cemented intervention had better outcomes regarding hip function, pain, and complications. Significant differences were found in terms of HHS at 6 weeks (WMD 12.5; 95% CI 6.0-17.0; P < 0.001), 3 months (WMD 3.3; 95% CI 1.6-5.0; P < 0.001), 4 months (WMD 7.3; 95% CI 3.4-11.2; P < 0.001), and 6 months (WMD 4.6; 95% CI 3.3-5.8; P < 0.001) postoperatively. Patients with cemented hemiarthroplasty had lower rates of pain (RR 0.59; 95% CI 0.39-0.9; P = 0.013), prosthetic fracture (RR 0.24; 95% CI 0.16-0.38; P < 0.001), subsidence/loosening (RR 0.29; 95% CI 0.11-0.78; P = 0.014), revisions (RR 0.59; 95% CI 0.40-0.89; P = 0.012), and pressure ulcers (RR 0.43; 95% CI 0.23-0.82; P = 0.01) at the expense of longer surgery time (WMD 7.87; 95% CI 5.71-10.02; P < 0.001). CONCLUSION: This meta-analysis demonstrated that patients with cemented hemiarthroplasty had better results in hip function and pain relief and lower complication rates at the expense of prolonged surgery time. Cemented hemiarthroplasty is recommended based on our findings.

Case report: Muscular tuberculosis with lower-extremity muscular masses as the initial presentation: Clinicopathological analysis of two cases and review of the literature.

Background: Tuberculosis (TB) is a threat to public health that mostly affects people in developing countries. TB presenting as a soft tissue mass is rare and is usually seen in patients with muscular tuberculosis (MT). Case presentation: In this study, we present the clinical, radiographic, and pathological features of two cases and retrospective evaluations of an additional 28 patients who were diagnosed with MT. More patients were men (60.9%) than women (39.1%), with a male-to-female ratio of 1.6:1. The average age among male and female patients was 38.9 and 30.1 years, respectively. MT usually presents with painful or painless muscular nodules on the lower limbs. Imaging findings, including ultrasound, CT, and MRI, can be used to identify lesions and sites for biopsy. The most typical histopathological feature of MT is granulomatous inflammation with caseous necrosis and epithelioid granulomata. Acid-fast bacilli stain and polymerase chain reaction (PCR) assays are helpful in identifying tubercle bacillus. Conclusion: We describe two MT cases with lower-extremity muscular masses as the initial presentation. The results suggest that muscle biopsy and pathological analysis remain necessary for diagnosis. Most of the patients could be cured with standard antituberculosis therapy.

Characterization of H2O2-Induced Alterations in Global Transcription of mRNA and lncRNA.

Hydrogen peroxide (H2O2) is an important reactive oxygen species that plays a major role in redox signaling. Although H2O2 is known to regulate gene expression and affect multiple cellular processes, the characteristics and mechanisms of such transcriptional regulation remain to be defined. In this study, we utilized transcriptome sequencing to determine the global changes of mRNA and lncRNA transcripts induced by H2O2 in human pancreatic normal epithelial (HPNE) and pancreatic cancer (PANC-1) cells. Promoter analysis using PROMO and TRRUST revealed that mRNAs and lncRNAs largely shared the same sets of transcription factors in response to ROS stress. Interestingly, promoters of the upregulated genes were similar to those of the downregulated transcripts, suggesting that the H2O2-responding promoters are conserved but they alone do not determine the levels of transcriptional outputs. We also found that H2O2 induced significant changes in molecules involved in the pathways of RNA metabolism, processing, and transport. Detailed analyses further revealed a significant difference between pancreatic cancer and noncancer cells in their response to H2O2 stress, especially in the transcription of genes involved in cell-cycle regulation and DNA repair. Our study provides new insights into RNA transcriptional regulation upon ROS stress in cancer and normal cells.

Deciphering the roles of miR-16-5p in malignant solid tumors.

MiR-16-5p, a member of the miR-16 family, has been reported to be abnormal expression in tumor tissues and blood of tumor patients, and also downregulated in most cancer cell lines. Aberrant expression of miR-16-5p promotes tumor cell proliferation, invasion, metastasis, angiogenesis, and can also affect the treatment sensitivity, such as radiotherapy and chemotherapy. Generally, miR-16-5p plays an anti-tumor role and these diverse functions of miR-16-5p in tumors collectively indicate that miR-16-5p may become an attractive target for novel anticancer therapies and a powerful diagnostic and prognostic biomarker for early tumor detection and population risk screening. Herein we review the role and utilization of miR-16-5p in malignant tumor in detail.

Expanding the clinical spectrum of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a heterogeneous neurodegenerative disease with multiple clinical subtypes. Recent breakthroughs on neuroimaging, skin biopsy and genetic testing have facilitated the diagnosis. We aim to investigate the clinical characteristics of Chinese NIID patients to further refine the spectrum. We analyzed the clinical features of 25 NIID patients from 24 unrelated families and performed skin biopsy and/or sural nerve biopsy on 24 probands. Repeat-primed PCR and fluorescence amplicon length PCR were conducted to detect GGC repeats of NOTCH2NLC. Onset age ranged from 24 to 72 years old, and the disease duration ranged from 12 h to 25 years with the mode of onset characterized as acute, recurrent or chronic progressive type. Tremor was a common phenotype, often observed in the early stages, next to dementia and paroxysmal encephalopathy. Symptoms infrequently reported such as oromandibular dystonia, recurrent vomiting, dizziness and headache of unknown origin, as well as pure peripheral neuropathy were also suggestive of NIID. Reversible leukoencephalopathy following encephalitic episodes and the absence of apparent DWI abnormality were noticed. Two genetically confirmed NIID patients failed to be identified intranuclear inclusions, and one patient was simultaneously found significant mitochondrial swelling and fingerprint profiles depositing in lysosomes. All the patients were identified abnormal GGC repeats of NOTCH2NLC. We identify some atypical clinicopathological features and consider that pathological examinations combined with genetic testing is the gold standard for diagnosis. Whether lysosomal and mitochondrial dysfunction is involved in the pathogenesis of NIID deserves further study.

An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.

Long non-coding RNA LEISA promotes progression of lung adenocarcinoma via enhancing interaction between STAT3 and IL-6 promoter.

Long non-coding RNAs (lncRNAs) are emerging as a new class of regulators for a variety of biological processes and have been suggested to play pivotal roles in cancer development and progression. Our current study found that a lncRNA, designated enhancing IL-6/STAT3 signaling activation (LEISA, ENST00000603468), functioned as an oncogenic lncRNA in lung adenocarcinoma (LAD), a major form of non-small cell lung carcinoma, which is one of the most frequently diagnosed malignancies with high morbidity and mortality worldwide, and was involved in the regulation of STAT3 induced IL-6 transcription. Our data showed that LEISA was highly expressed in, and correlated with the clinical progression and prognosis of LAD. Ectopic expression of LEISA promoted the proliferation and suppressed apoptosis of LAD cells in vitro and in vivo. Mechanistically, we demonstrated that LEISA recruited STAT3 to bind the promoter of IL-6 and upregulated IL-6 expression. Taken together, our work identifies LEISA as a potential diagnostic biomarker and therapeutic target for LAD.

Proximity binding-triggered multipedal DNA walker for the electrochemiluminescence detection of telomerase activity.

The sensitive detection of telomerase activity is of great significance for the early diagnosis and treatment of cancer. Here, an innovative electrochemiluminescence resonance energy transfer (ECL-RET) sensor was explored to reliably detect telomerase activity based on proximity binding-triggered multipedal DNA walker. In this system, CdS quantum dots (CdS QDs) and silver nanoclusters (Ag NCs) were applied as ECL donor and acceptor, respectively. By ingeniously introducing a repetitive bases sequence (TTAGGG) along the telomerase primer, multiple same DNA "legs" were formed, leading to the activation of proximity binding-triggered multipedal DNA walker. Unlike the traditional unipedal DNA walker, one walking step of multipedal DNA walker concurrently initiated the responsivity of multiple signals, resulting in the shortening of the walking time and improvement of the signal amplification efficiency. Thus, under optimal conditions, the designed ECL-RET sensor exhibited a wide dynamic correlation of HeLa cells' telomerase activity from 1 × 102 to 1 × 106 cells/mL and a low detection limit of 16 cells/mL. Moreover, this sensor realized the general and reliable analysis of telomerase activity in different cell lines. Due to the outstanding application potential in real samples, it is believed that the ECL-RET sensing system provides a new approach for the application of telomerase activity assays in cancer diagnostics.

Prognostic Value of Pro-Inflammatory Neutrophils and C-Reactive Protein in Cancer Patient With Coronavirus Disease 2019: A Multi-Center, Retrospective Study.

Background: At present, the epidemic of the novel coronavirus disease 2019 (COVID-19) has quickly engulfed the world. Inflammatory cytokines are associated with the severity and outcomes of patients with COVID-19. However, the prognostic value of pro-inflammatory factors in cancer patients with COVID-19 are unknown. Methods: A multi-center, retrospective, cross-sectional study, based on five designated tertiary hospitals for the treatment of COVID-19 in Hubei Province, China. 112 cancer patients with COVID-19, and 105 COVID-19 patients without cancer were enrolled in the study between January 1st, 2020 and April 30th, 2020. The risk assessment of pro-inflammatory factors for disease severity and clinical adverse outcomes was identified by univariable and multivariable logistic regression models. Results: Of the 112 cancer patients with COVID-19, 40 (35.7%) patients were in critical condition and 18 (16.1%) patients died unfortunately. Univariate and multivariate analysis demonstrated that hemoglobin level and pro-inflammatory neutrophils and C-reactive protein (CRP), can be used as independent factors affecting the severity of COVID-19; Meanwhile, pro-inflammatory neutrophils and CRP can be used as an independent influencing factor for adverse clinical outcome of death. Moreover, the dynamic changes of neutrophils and CRP were also presented, and compared with COVID-19 patients without cancer, cancer patients with COVID-19 showed higher neutrophil counts and CRP levels. Conclusion: In cancer patients with COVID-19, the significant increase in pro-inflammatory neutrophils and CRP indicated a more critical illness and adverse clinical outcome, and pro-inflammatory neutrophils and CRP played a greater adverse role compare with COVID-19 patients without cancer, which may be the cause of critical illness and adverse clinical outcomes of cancer patients with COVID-19.

Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy.

BACKGROUND: CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. METHODS: In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. RESULTS: Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24-46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. CONCLUSIONS: Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. TRIAL REGISTRATION: ChiCTR, ChiCTR1800015295. Registered 21 March 2018.

Long noncoding RNA LINC00673-v4 promotes aggressiveness of lung adenocarcinoma via activating WNT/ß-catenin signaling.

It is well recognized that metastasis can occur early in the course of lung adenocarcinoma (LAD) development, and yet the molecular mechanisms driving this capability of rapid metastasis remain incompletely understood. Here we reported that a long noncoding RNA, LINC00673, was up-regulated in LAD cells. Of note, we first found that LINC00673-v4 was the most abundant transcript of LINC00673 in LAD cells and its expression was associated with adverse clinical outcome of LAD. In vitro and in vivo experiments demonstrated that LINC00673-v4 enhanced invasiveness, migration, and metastasis of LAD cells. Mechanistically, LINC00673-v4 augmented the interaction between DDX3 and CK1ε and thus the phosphorylation of dishevelled, which subsequently activated WNT/ß-catenin signaling and consequently caused aggressiveness of LAD. Antagonizing LINC00673-v4 suppressed LAD metastasis in vivo. Together, our data suggest that LINC00673-v4 is a driver molecule for metastasis via constitutively activating WNT/ß-catenin signaling in LAD and may represent a potential therapeutic target against the metastasis of LAD.

LncRNA DUXAP9-206 directly binds with Cbl-b to augment EGFR signaling and promotes non-small cell lung cancer progression.

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9-206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9-206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl-b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9-206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9-206 in mediating the progression of NSCLC and DUXAP9-206 may serve as a potential target for NSCLC therapy.

EGF-induced nuclear localization of SHCBP1 activates ß-catenin signaling and promotes cancer progression.

Aberrant activation of EGFR represents a common event in non-small cell lung carcinoma (NSCLC) and activates various downstream signaling pathways. While EGFR activation of ß-catenin signaling was previously reported, the mediating mechanism remains unclear. Our current study found that EGFR activation in NSCLC cells releases SHC-binging protein 1 (SHCBP1) from SHC adaptor protein 1 (SHC1), which subsequently translocates into the nucleus and directly promotes the transactivating activity of ß-catenin, consequently resulting in development of NSCLC cell stemness and malignant progression. Furthermore, SHCBP1 promotes ß-catenin activity through enhancing the CBP/ß-catenin interaction, and most interestingly, a candidate drug that blocks the CBP/ß-catenin binding effectively abrogates the aforementioned biological effects of SHCBP1. Clinically, SHCBP1 level in NSCLC tumors was found to inversely correlate with patient survival. Together, our study establishes a novel convergence between EGFR and ß-catenin pathways and highlights a potential significance of SHCBP1 as a prognostic biomarker and a therapeutic target.

Assessment of the health risks and odor concentration of volatile compounds from a municipal solid waste landfill in China.

Municipal solid waste (MSW) landfills are a source of odorous and toxic compounds. In this work, we present an integrated assessment of the odor concentration and human health risks of volatile compounds to evaluate the environmental quality at a MSW landfill. Air samples were collected seasonally from six areas of the landfill with different functions. The total concentrations of the compounds ranged from 204.0 to 7426.7 µg m-3, and the concentrations in temporarily and permanently capped areas were 50.3 and 83.4% lower than those in the tipping area, respectively. The odor concentration was greatest at the leachate collection tank (1732-6254 ouE m-3) and tipping area (1573-4113 ouE m-3) and was mainly caused by hydrogen sulfide (57.9 and 49.1%, respectively). Moreover, the odor concentration was positively correlated with the temperature (r = 0.500, p < 0.05, n = 24). Although the non-carcinogenic (HI) and carcinogenic (R) risks of most compounds were largely below the acceptable levels (HI = 1, R = 1.0E-6), HI values of hydrogen sulfide (2.3), trichloropropane (2.0), and naphthalene (1.2) as well as R values of naphthalene (1.3E-4) and trimethylbenzene (1.2E-4) in the waste areas exceeded acceptable levels. Moreover, the cumulative HI (2.5-5.7) and R (1.0E-04 to 3.4E-04) in the waste areas should receive special attention since they were above acceptable levels during all of the seasons. Aromatic and halogenated compounds dominated the cumulative R, accounting for 79 and 21% of the total, on average, while for the cumulative HI, sulfur compounds contributed the most (67%).

Synthesis, characterization, and study on HeLa cells activity of a dinuclear complex [Cu4(phen)4(H2O)2]·(pyri)·3H2O.

The complex [Cu4(phen)4(H2O)2]·(pyri)·3H2O(where phen=1,10-phenanthroline and pyri=3,5-pyridine dicarboxylic acid)has been synthesized and characterized. IR spectra, elemental analysis and X-ray single-crystal diffraction were carried out to determine the composition and crystal structure of the complex. The binding of the complex with HC-DNA (HeLa cells DNA, which was extracted by ourselves) was investigated by fluorescence spectrum. Gel electrophoresis assay demonstrates the ability of the complex to cleave the extracted HC-DNA. Additionally, the complex exhibited a significant cytotoxic specificity and cancer cell inhibitory rate. The apoptotic tests indicate that the complex have an apoptotic effect on HeLa cells.

Synthesis, characterization, interaction with DNA and cytotoxicity in vitro of novel pyridine complexes with Zn(II).

Four novel Zn(II) complexes [Zn(L(1))(bipy)(H(2)O)(2)].4H(2)O(1), [Zn(L(1))(phen)(H(2)O)(2)].4H(2)O(2), [Zn(L(2))(bipy)(H(2)O)(2)].4H(2)O(3) and [Zn(L(2))(phen)(H(2)O)(2)].4H(2)O (4), where bipy=2,2'-bipyridine, phen=1,10-phenanthroline, L(1)=2,2'-bipyridine 5,5'-dicarboxylic acid, L(2)=2,2'-bipyridine-4,4'-dicarboxylic acid, have been synthesized and characterized using IR, (1)H NMR, element analysis and single-crystal X-ray diffractometry. The unit cell parameters for the title complex (1), a=7.9621(10)A, b=12.6853(17)A, c=13.3714(17)A, alpha=68.549(2) degrees , beta=79.065(2) degrees , gamma=88.723(2) degrees , V=1232.5(3)A(3), Z=15, space group,P-1(2).complex (4) a=9.5710(5)A, b=14.1140(7)A, c=19.0045(9)A, alpha=90 degrees , beta=99.9920(10) degrees , gamma=90 degrees , V=2528.3(2)A(3), Z=32, space group, P121/n 1(14). The binding of the complexes with fish sperm DNA (FS-DNA) was investigated by electronic absorption spectra and fluorescence spectroscopy, showing that the complexes have the ability of interaction with DNA of intercalative mode. The intrinsic binding constant K of the complexes with FS-DNA is 0.37 x 10(5)M(-1) (1) 0.73 x 10(5)M(-1) (2), 0.98 x 10(5)M(-1) (3), and 1.05 x 10(5)M(-1) (4). The results indicate that the four complexes bound to DNA with different binding affinity, in the order complex 4>3>2>1. Gel electrophoresis assay demonstrates the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the complexes was tested against four different cancer cell lines. The four complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate.

[The expression of periphery blood leucocyte CCR3 and CCR5 in the children with Epstein-Barr virus associated infectious mononucleosis].

OBJECTIVE: To explore the expression of periphery blood leucocyte CCR3 and CCR5 and to comprehend T helper cell in the Children with Epstein-Barr virus associated infectious mononucleosis. METHODS: We defined the children according to the diagnosis criterion through Paul-Bunnell test inspecting the children's periphery blood unusual lymphocyte and detecting their anti-EBV-CA-IgM, anti-EBV-CA-IgG and anti-EBV-NA-IgG by ELISA and counted the ratio of CCR3 + and CCR5 + cells in lymphocytes with flow cytometry. RESULTS: The ratio of unusual lymphocyte in IM was higher than that of the healthy control group (P < 0.05). The ratio of CCR3 + cells in IM group was higher than that of the healthy control group (P < 0.05). The ratio of CCR5 + cells in IM group was significantly lower than that of the healthy control group. CCR3 + had direct interrelation with fever continued time and the ratio of unusual lymphocyte. There was a negative interrelation between CCR5 and fever continued time (P < 0.05). CONCLUSIONS: Children infectious of IM expressed higher level of CCR3 + and lower level of CCR5 + and there was a tendency of Th2 polarization with over production of T helper cell divide imbalance. CCR3 + and CCR5 + may be important targets to judge the degree of seriousness of IM.