Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Irisflorentin promotes bacterial phagocytosis and inhibits inflammatory responses in macrophages during bacterial infection.

Bacterial infection remains a big concern in the patients of ICU, which is the main cause of life-threatening organ dysfunction, or even sepsis. The poor control of bacterial infection caused by antibiotic resistance, etc. or the overwhelming immune response are the most important patho genic factors in intensive care unit (ICU) patients. As main pathogens, antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), impose serious challenges during sepsis and require alternative therapeutic options. Irisflorentin (IFL) is one of the major bioactive compounds isolated from the roots of Belamcanda chinensis (Shegan). In this study, IFL could suppress inflammatory response induced by MRSA or a synthetic mimic of bacterial lipoprotein (Pam3CSK4). IFL treatment enhanced the ability of macrophages to phagocytose bacteria likely through up-regulating the expression of phagocytic receptors SR-A1 and FcγR2a. Furthermore, IFL inhibited Pam3CSK4-induced production of pro-inflammatory cytokines, including IL-6 and TNF-α in Raw 264.7 cells, mouse primary macrophages or dendritic cells. IFL treatment also inhibited heat-killed MRSA-induced secretion of IL-6 and TNF-α in mouse bone marrow-derived macrophages. Moreover, IFL attenuated M1 polarization of macrophages as indicated by the down-regulated expression of its polarization markers CD86 and iNOS. Mechanistically, IFL markedly decreased the Pam3CSK4-induced activation of ERK, JNK or p38 MAPK pathways in macrophages. Taken together, IFL may serve as a promising compound for the therapy of bacterial infection, particularly those caused by antibiotic-resistant bacteria, such as MRSA.

The insulin long-acting chitosan - Polyethyleneimine nanoparticles to treat the type 2 diabetes mellitus and prevent the associated complications.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, which is ultimately treated by the insulin (INS). However, the subcutaneous (s. c.) injection of insulin solution faces the problems of pain and unsatisfactory patient compliance. In this study, the long-acting formulations of insulin are propsed to treat the T2DM and prevent the associated complications. The chitosan (CS) and/or branched polyethyleneimine (bPEI) nanoparticles (bPEI-INS NPs, CS-bPEI-INS NPs) were constructed to load insulin. The long -acting nanoparticles successfully achieved the sustained release of the INS in vitro and in vivo. After s. c. administration, the CS-bPEI-INS NPs greatly improved the INS bioavailability. As a result, the CS-bPEI-INS NPs produced sustained glucose-lowering effects, promising short-term and long-term hypoglycemic efficacy in the T2DM model. Furthermore, the treatment of the CS-bPEI-INS NPs greatly protected the islet in the pancreas and prevented the associated complications of the T2DM, such as cardiac fibrosis in the myocardial interstitium and the perivascular area. In a word, the CS-bPEI-INS NPs was an encouraging long-acting formulation of insulin and had great potential in the treatment of T2DM.

Safety and efficacy of prostatic artery embolization for large benign prostatic hyperplasia in elderly patients.

OBJECTIVE: To assess the safety and efficacy of prostatic arterial embolization (PAE) for elderly patients with lower urinary tract symptoms secondary to large benign prostatic hyperplasia. METHODS: Twenty-eight patients (>80 years of age) with prostate volume >80 mL were enrolled from October 2016 to October 2019. PAE was performed using microspheres and functional results were evaluated at 1, 3, 6, and 12 months postoperatively. The following data were recorded: International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urine flow rate (Qmax), post-void residual urine volume, prostate volume and total prostate-specific antigen level. RESULTS: Selective prostatic arterial catheterization and embolization were achieved in 27 of 28 patients. Follow-up data were available for those 27 patients until 12 months postoperatively. Significant improvements were found at all postoperative time points in terms of the mean IPSS, mean QoL score, mean Qmax, mean post-void residual urine volume, mean total prostate-specific antigen level, and mean prostate volume. The overall complication rate was 46.4%. CONCLUSIONS: PAE is an efficacious and safe treatment for elderly patients with large prostate volume; it may offer an effective approach for patients who are not candidates for open or endoscopic surgical procedures because of comorbidities.

miR-1246 shuttling from fibroblasts promotes colorectal cancer cell migration.

Cancer-associated fibroblasts (CAFs) are the major constituents of the tumor microenvironment and promote cancer development via tumor-stromal interactions. The alteration of microRNA (miRNA) expression in fibroblasts can induce the phenotype conversion between normal fibroblasts and CAFs in certain tumor types. However, the mechanisms underlying the phenotype conversion of fibroblasts in colorectal cancer (CRC) are largely unknown. Our study focuses on the role of miR-1246 in fibroblasts-CRC cells interaction. In this study, CCD-18Co colorectal fibroblasts were cultured in the conditioned medium (CM) derived from CRC cells to obtain the CAF phenotype. We found that the miR-1246 expression was upregulated in CAF-like fibroblasts compared with normal fibroblasts. miR-1246 secreted by cancer cells could be utilized by neighboring fibroblasts for CAF reprogramming. On the other hand, following secretion by CAF-like fibroblasts, miR-1246 was delivered into CRC cells and promoted cell migration via the activation of the Wnt/ß-catenin signaling in CRC cells. Furthermore, high miR-1246 expression in CRC tissues was negatively associated with disease-free survival (DFS) for CRC patients. Taken together, our results reveal that miR-1246 can shuttle between CRC cells and fibroblasts. This study also indicates that targeting miR-1246 or blocking its transport from CAFs to CRC cells might represent a novel therapeutic approach in CRC treatment.

Air-Induced Degradation and Electrochemical Regeneration for the Performance of Layered Ni-Rich Cathodes.

Nickel-rich layered oxides are promising cathodes for power batteries owing to their high capacity and low cost. However, during the production, storage, and application of nickel-rich cathodes, especially in case the Ni content exceeds 70%, their surfaces almost inevitably react with ambient air to form electrochemically inert Li2CO3 and LiOH, leading to significant capacity loss and therefore imposing a significant hurdle to practical applications of nickel-rich cathodes. Here, we reveal surface structures and electrochemical properties of the exposed LiNi0.8Co0.15Al0.05O2 (NCA) cathodes and investigate systematically the impact of exposure humidity, temperature, and time on NCA cathodes. We demonstrate that introduction of a 3.0-4.5 V galvanostatic cycling operation at initial cycles can remarkably regenerate the subsequent 3.0-4.3 V battery performances of the exposed cathode. This work represents a facile method to regenerate the battery performance of surface-degraded nickel-rich cathodes, opening up an avenue in fulfilling efficient production, storage, and application of nickel-rich cathode materials.

Formation and Effect of Residual Lithium Compounds on Li-Rich Cathode Material Li1.35[Ni0.35Mn0.65]O2.

Li-rich cathode materials are regarded as ideal cathode materials, owing to their excellent electrochemical capacity. However, residual lithium compounds, which are formed on the surface of the materials by reacting with moisture and carbon dioxide in ambient atmosphere, can impair the surface structure, injure the capacity, and impede the electrode fabrication using Li-rich materials. Exposure to air atmosphere causes the formation of residual lithium compounds; the formation of such compounds is believed to be related to humidity, temperature, and time during handling and storage. In this study, we demonstrated for the first time an artificial strategy for controlling time, temperature, and humidity to accelerate exposure. The formation and effect of residual lithium compounds on Li-rich cathode material Li1.35[Ni0.35Mn0.65]O2 were systematically investigated. The residual lithium compounds formed possessed primarily an amorphous structure and were partially coated on the surface. These compounds include LiOH, Li2O, and Li2CO3. Li2CO3 is the major component in residual lithium compounds. The presence of residual lithium compounds on the material surface led to a high discharge capacity loss and large discharge voltage fading. Understanding the formation and suppressing the effect of residual lithium compounds will help prevent their unfavorable effects and improve the electrochemical performance.

Room-temperature solution synthesis of ZnMn2O4 nanoparticles for advanced electrochemical lithium storage.

Taking advantage of synergistic effects, the ternary metal oxides have attracted tremendous interest. Herein, ZnMn2O4 nano-particles have been fabricated via a facile one-step approach at room temperature, that of simply mixing ZnO and MnO in KOH aqueous solution without templates. When used as an anode for lithium ion batteries, it delivers the excellent structure stability (1028.9 mA h g-1 at 1.0 A g-1 after 400 cycles). Surprisingly, the low-cost and eco-friendly route provides a novel strategy to synthesize the mixed transition metal oxide electrodes with readily scaled-up production.

Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy.

Targeting macroautophagy/autophagy is a novel strategy in cancer immunotherapy. In the present study, we showed that the natural product rocaglamide (RocA) enhanced natural killer (NK) cell-mediated lysis of non-small cell lung cancer (NSCLC) cells in vitro and tumor regression in vivo. Moreover, this effect was not related to the NK cell recognition of target cells or expressions of death receptors. Instead, RocA inhibited autophagy and restored the level of NK cell-derived GZMB (granzyme B) in NSCLC cells, therefore increasing their susceptibility to NK cell-mediated killing. In addition, we further identified that the target of RocA was ULK1 (unc-51 like autophagy activating kinase 1) that is required for autophagy initiation. Using firefly luciferase containing the 5´ untranslated region of ULK1, we found that RocA inhibited the protein translation of ULK1 in a sequence-specific manner. Taken together, RocA could block autophagic immune resistance to NK cell-mediated killing, and our data suggested that RocA was a promising therapeutic candidate in NK cell-based cancer immunotherapy.

Structure-based discovery of selective BRPF1 bromodomain inhibitors.

Bromodomain and plant homeodomain (PHD) finger containing protein 1 (BRPF1) is a member of subfamily IV of the human bromodomains. Experimental evidence suggests that BRPF1 is involved in leukemia. In a previous high-throughput docking campaign we identified several chemotypes targeting the BRPF1 bromodomain. Here, pharmacophore searches using the binding modes of two of these chemotypes resulted in two new series of ligands of the BRPF1 bromodomain. The 2,3-dioxo-quinoxaline 21 exhibits a 2-µM affinity for the BRPF1 bromodomain in two different competition binding assays, and more than 100-fold selectivity for BRPF1 against other members of subfamily IV and representatives of other subfamilies. Cellular activity is confirmed by a viability assay in a leukemia cell line. Isothermal titration calorimetry measurements reveal enthalpy-driven binding for compounds 21, 26 (KD = 3 µM), and the 2,4-dimethyl-oxazole derivative 42 (KD = 10 µM). Multiple molecular dynamics simulations and a dozen co-crystal structures at high resolution provide useful information for further optimization of affinity for the BRPF1 bromodomain.

MiR-650 represses high-risk non-metastatic colorectal cancer progression via inhibition of AKT2/GSK3ß/E-cadherin pathway.

Although 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo. Furthermore, miR-650 targeted AKT2 and repressed the activation of the AKT pathway (AKT2/GSK3ß/E-cadherin). Thus it induced the translocation of E-cadherin and ß-catenin in cancer cells. Our results highlight the potential of miR-650 as a prognostic prediction biomarker and therapeutic target in non-metastatic CRC via inhibition of the AKT2/GSK3ß/E-cadherin pathway.

AMPK-autophagy inhibition sensitizes icaritin-induced anti-colorectal cancer cell activity.

The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis. Icaritin activated AMP-activated protein kinase (AMPK) signaling in CRC cells, functioning as the upstream signaling for autophagy activation. shRNA/siRNA-mediated knockdown of AMPKα1inhibited icaritin-induced autophagy activation, but exacerbated CRC cell death. On the other hand, the AMPK activator compound 13 (C13) or the autophagy activator MHY1485 attenuated icaritin-induced cytotoxicity. In nude mice, icaritin (oral administration)-induced HT-29 tumor growth inhibition was potentiated when combined with AMPKα1 shRNA knockdown in tumors. We conclude that feedback activation of AMPK-autophagy pathway could be a primary resistance factor of icaritin.

miR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes.

Accumulating evidence has shown that aberrantly expressed microRNAs (miRNAs) are associated with tumor development and progression. Our previous study found that microRNA-375 (miR-375) was downregulated in colorectal cancer (CRC), but little is known concerning the role of miR-375 and the related mechanism in CRC development. The proliferation, invasion and migration effects were investigated by Cell Counting Kit-8 (CCK-8), colony formation and Transwell assays with or without Matrigel. In addition, candidate target genes were screened and validated by luciferase reporter and western blot assays. In addition, western blot analysis was performed to explore the molecular mechanisms associated with epithelial­mesenchymal transition (EMT). It was found that miR-375 inhibited proliferation, invasion and migration in DLD1 and HCT8 cells. In addition, miR-375 negatively regulated Sp1 transcription factor (SP1) protein by directly binding to the 3'-untranslated region (3'-UTR). Furthermore, it was found that miR-375 regulated matrix metalloproteinase 2 (MMP2) and EMT-associated genes, E-cadherin, vimentin, snail, N-cadherin and ß-catenin. In conclusion, miR-375 inhibited the proliferation, invasion and migration by directly targeting SP1 and regulating MMP2 and EMT-associated genes.

Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells.

The colorectal cancer (CRC) is one leading contributor of cancer-related mortality worldwide. The search for effective anti-CRC agents is valuable. In the current study, we showed that icaritin (ICT), an active natural ingredient from the Chinese plant Epimedium, potently inhibited proliferation and survival of established (HT-29, HCT-116, DLD-1, and SW-620) and primary (patient-derived) CRC cells. Significantly, ICT mainly induced necrosis, but not apoptosis, in CRC cells. The necrosis inhibitor necrostatin-1 attenuated ICT-mediated cytotoxicity in CRC cells. We showed that ICT treatment in CRC cells induced mitochondrial permeability transition pore (mPTP) opening, which was evidenced by mitochondrial membrane potential (MMP) decrease and mitochondrial adenine nucleotide translocator-1 (ANT-1)-cyclophilin-D (CyPD) association. On the other hand, mPTP blockers, including sanglifehrin A, cyclosporin A, and bongkrekic acid, as well as siRNA-mediated knockdown of mPTP component (CyPD or ANT-1), significantly alleviated ICT-mediated cytotoxicity against CRC cells. We suggested that Jun-N-terminal kinase (JNK) activation by ICT mediated mPTP opening and subsequent CRC cell necrosis. JNK pharmacological inhibition, dominant negative mutation, or shRNA downregulation suppressed ICT-induced MMP reduction and subsequent HT-29 cell necrosis. In vivo, oral gavage of ICT dramatically inhibited HT-29 xenograft growth in nude mice. The in vivo activity by ICT was largely attenuated by co-administration with the mPTP blocker CsA. Collectively, our results showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK-dependent mPTP necrosis pathway could be key mechanism responsible for ICT's actions.

[Effect of linear alkylbenzenesulfonate on the reproductive capacity and life-span of Drosophila melanogaster].

OBJECTIVE: To investigate the effect of linear alkylbenzenesulfonate (LAS) on the reproductive capacity and life-span of Drosophila melanogaster. METHODS: Drosophila melanogaster images within 8 h after eclosion were collected with ether anesthesia. The female and male of similar size and normal shape and behavior were selected. The Drosophila melanogasters were cultured in the culture medium containing LAS of different densities. We divided the Drosophila melanogaster into 4 groups according to LAS concentrations: a low dose group with LAS 150 mg/kg, a middle dose group with LAS 300 mg/kg,a high dose group with LAS 600 mg/kg, and a control group without LAS, respectively. The changes of the reproductive capacity, median lethal time, mean life-span and max mean life-span of drosophila melanogaster with different doses of LAS were measured and compared with those of the control. RESULTS: The pupa numbers of filial generation of Drosophila melanogaster in the low, middle, and high dose groups (85.07%, 84.59% and 71.88%, respectively) were lower than those in the control group (P<0.01). The median lethal time, mean life-span and max mean life-span of Drosophila melanogaster in the low, middle, and high dose groups were shorter than those in the control group (P<0.05). The change of life-span of Drosophila melanogaster in the high dose group was remarkable: the median lethal time of female and male shortened 13 days and 15 days, the mean life-span of female and male shortened 18 days and 14 days, and the max mean life-span of female and male shortened 14 days and 12 days, respectively. CONCLUSION: LAS has definite toxicity to Drosophila melanogaster, which can degrade the reproductive capacity of Drosophila melanogaster and shorten the life-span of Drosophila melanogaster.

[Association of sub-health symptoms with family environment factors in middle school students in Bengbu District].

OBJECTIVE: To describe the prevalence of psychosomatic sub-health symptoms in middle school students and to explore the related family factors affecting the sub-health symptoms. METHODS: Based on stratified, random cluster sampling method, 2 910 students from 6 middle schools in Bengbu district were sampled. Questionnaire on demographic characteristics and family factors, and the multidimensional sub-health questionnaire of adolescents (MSQA) were used to investigate the risk factors of sub-health symptoms. RESULTS: The prevalence of overall sub-health symptoms was reported in 64.0% of students, physical symptoms was reported in 13.6% of the students, and the rates of physical inactivity, physiological dysfunction and immunity decline were in 53.0%, 68.7% and 55.0% of students respectively. Mental sub-health symptoms were reported in 55.4% of students, emotional symptoms, behavioral symptoms and social adaptation problems were reported in 78.4%, 51.5% and 85.6% of students respectively. There was an increase in the prevalence of self-reported sub-health symptoms with the increase of the grade (P < 0.05), boys were more likely to report sub-health symptoms than girls (65.7% vs. 62.0%, P < 0.05). The main family factors affecting sub-health symptom of students were the health status of their parents and major accompanying persons. CONCLUSION: The prevalence rate of sub-health symptoms in middle school students was very high and increased with the length of time and the grade at school. The risk factors for sub-health symptoms of students were the lower health level of their parents and not their parents accompanying them.

[Relation between sub-health and family environmental factors among university students in Bengbu city].

OBJECTIVE: : To describe the prevalence of psychosomatic sub-health symptoms and to explore the effects of family factors on them among university students. METHODS: Based on stratified, convenience cluster sampling, questionnaire investigation was conducted among 320 students from 2 universities of Bengbu city, which contained demographic characteristics, family factors and multidimensional sub-health questionnaire of adolescents (MSQA). Chi2 test and Logistic regression analysis were used to examine the risk factors of sub-health symptoms. RESULTS: The prevalence of overall sub-health symptoms among students was 46.0%. Of the students 30.0% reported physical symptoms and the rates of physical inactivity, physiological dysfunction, and immunity decline were 27.0%, 42.0% and 34.1%, respectively. Of the students 36.5% reported mental symptoms and the rates emotional symptoms, behavioral symptoms and social adaptation problems were 68.6, 35.5% and 85.8%, respectively. The main family factors influence sub-health symptom were family type and the health status of parents. CONCLUSION: The prevalence rate of sub-health symptoms among university students was very high. The risk factors for sub-health symptoms were single-parent family and lower health level of parents .

A comparative study of using comet assay and gammaH2AX foci formation in the detection of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA damage.

Comet assay is a useful technique in the detection of DNA damages, particularly DNA strand breaks; and it has been utilized to show that a potent carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), can induce such damages. Recently, gammaH2AX foci formation has been suggested as another sensitive way to detect DNA double strand breaks (DSBs). However, there is no systematic comparison being conducted to evaluate the consistency of these two methods. Using MNNG as a model chemical, the sensitivity of neutral comet assay and gammaH2AX foci formation in detecting MNNG-induced damage was studied. It was found that at concentrations of 0.1 and 1 microg/ml, both methods can detect MNNG-induced damage in human amnion FL cells. However, at 0.1 microg/ml, comet assay revealed more percentage of cells with DNA damage than gammaH2AX fluorescence revealed. On the other hand, while gammaH2AX foci were readily formed at very early times by 10 microg/ml MNNG treatment, neutral comet assay did not detect any significant DNA damage at the same time points. In addition, 10 microg/ml MNNG induced a distinct whole nuclei staining pattern of gammaH2AX, a type of DNA damage which was not detected by neutral comet assay but could be detected by alkaline comet assay. Therefore, gammaH2AX may be used as a sensitive indicator for DNA damage.

DNA damage evaluated by gammaH2AX foci formation by a selective group of chemical/physical stressors.

It has been reported that the phosphorylated form of histone variant H2AX (gammaH2AX) plays an important role in the recruitment of DNA repair and checkpoint proteins to sites of DNA damage, particularly at double strand breaks (DSBs). Using gammaH2AX foci formation as an indicator for DNA damage, several chemicals/stress factors were chosen to assess their ability to induce gammaH2AX foci in a 24h time frame in a human amnion FL cell line. Two direct-acting genotoxins, methyl methanesulfonate (MMS) and N-ethyl-N-nitrosourea (ENU), can induce gammaH2AX foci formation in a time- and dose-dependent manner. Similarly, an indirect-acting genotoxin, benzo[a]pyrene (BP), also induced the formation of gammaH2AX foci in a time- and dose-dependent manner. Another indirect genotoxin, 2-acetyl-aminofluorene (AAF), did not induce gammaH2AX foci formation in FL cells; however, AAF can induce gammaH2AX foci formation in Chinese hamster CHL cells. Neutral comet assays also revealed the induction of DNA strand breaks by these agents. In contrast, epigenetic carcinogens azathioprine and cyclosporine A, as well as non-carcinogen dimethyl sulfoxide, did not induce gammaH2AX foci formation in FL cells. In addition, heat shock and hypertonic saline did not induce gammaH2AX foci. Cell survival analyses indicated that the induction of gammaH2AX is not correlated with the cytotoxic effects of these agents/factors. Taken together, these results suggest that gammaH2AX foci formation could be used for evaluating DNA damage; however, the different cell types used may play an important role in determining gammaH2AX foci formation induced by a specific agent.