Dynamic transcriptome profiling revealed a key gene ZmJMJ20 and pathways associated with cadmium stress in maize.

Cadmium (Cd) pollution in soil poses a global concern due to its serious impacts on human health and ecological security. In plants, tremendous efforts have been made to identify some key genes and pathways in Cd stress responses. However, studies on the roles of epigenetic factors in response to Cd stress were still limited. In the study, we first gain insight into the gene expression dynamics for maize seedlings under 0 h, 12 h, and 72 h Cd stress. As a result, six distinct groups of genes were identified by hierarchical clustering and principal component analysis. The key pathways associated with 12 h Cd stress were protein modifications including protein ubiquitination, signal transduction by protein phosphorylation, and histone modification. Whereas, under 72 h stress, main pathways were involved in biological processes including phenylalanine metabolism, response to oxygen-containing compounds and metal ions. Then to be noted, one of the most highly expressed genes at 12 h under Cd treatment is annotated as histone demethylases (ZmJMJ20). The evolutionary tree analysis and domain analysis showed that ZmJMJ20 belonged to the JmjC-only subfamily of the Jumonji-C (JmjC) family, and ZmJMJ20 was conserved in rice and Arabidopsis. After 72 h of Cd treatment, the zmjmj20 mutant created by EMS treatment manifested less severe chlorosis/leaf yellowing symptoms compared with wild-type plants, and there was no significant difference in Fv/Fm and φPSII value before and after Cd treatment. Moreover, the expression levels of several photosynthesis-related down-regulated genes in EMS mutant plants were dramatically increased compared with those in wild-type plants at 12 h under Cd treatment. Our results suggested that ZmJMJ20 plays an important role in the Cd tolerance response pathway and will facilitate the development of cultivars with improved Cd stress tolerance.

Ammonium tetrathiomolybdate triggers autophagy-dependent NRF2 activation in vascular endothelial cells.

Ammonium tetrathiomolybdate (TTM) is a copper chelator in clinical trials for treatment of Wilson's disease, tumors and other diseases. In the current study, we innovatively discovered that TTM is a novel NRF2 activator and illustrated that autophagy contributed to TTM-induced NRF2 activation. We showed that TTM treatment promoted NRF2 nuclear translocation and upregulated transcription level of NRF2 target genes including HMOX1, GCLM, and SLC7A11 in vascular endothelial cells (HUVECs). Moreover, NRF2 deficiency directly hindered TTM-mediated antioxidative effects. Followingly, we revealed that overexpression of KEAP1, a negative regulator of NRF2, significantly repressed NRF2 activation induced by TTM. Further mutation analysis revealed that KEAP1 Cys151 is a major sensor responsible for TTM-initiated NRF2 signaling, suggesting that KEAP1 is involved in TTM-mediated NRF2 activation. Notably, we found that TTM can trigger autophagy as evidenced by accumulation of autophagosomes, elevation of LC3BI-II/I, increase of LC3 puncta and activation of AMPK/mTOR/ULK1 pathway. Autophagic flux assay indicated that TTM significantly enhanced autophagic flux in HUVECs. Inhibition of autophagy with knockout of autophagy key gene ATG5 resulted in suppression of TTM-induced NRF2 activation. TTM also induced phosphorylation of autophagy receptor SQSTM1 at Ser349, while SQSTM1-deficiency inhibited KEAP1 degradation and blocked NRF2 signaling pathway, suggesting that TTM-induced NRF2 activation is autophagy dependent. As the novel NRF2 activator, TTM protected against sodium arsenite (NaAsO2)-induced oxidative stress and cell death, while NRF2 deficiency weakened TTM antioxidative effects. Finally, we showed that autophagy-dependent NRF2 activation contributed to the protective effects of TTM against NaAsO2-induced oxidative injury, because of ATG5 or SQSTM1 knockout aggravated NaAsO2-induced elevation of HMOX1, cleaved PARP and γH2AX. Taken together, our findings highlight copper chelator TTM is a novel autophagy-dependent NRF2 activator and shed a new light on the cure for oxidative damage-related diseases.

The cost-effectiveness of bivalent, quadrivalent, and nine-valent HPV vaccination in Asia: a systematic review.

PURPOSE: The aim of this study was to systematically review the cost-effectiveness of HPV vaccination in Asia. METHODS: We performed a systematic review of papers indexed in PubMed, Scopus, and Web of Science covering the period from 1 January 2000 to 13 August 2020. RESULTS: Sixteen studies were included in the review. Half of them (8 studies) evaluated the cost-effectiveness of HPV vaccination in high-income countries and regions (HICs) while the other eight studies were set in low- and middle-income countries and regions (LMICs). In HICs, the implementation of bivalent, quadrivalent and nine-valent HPV vaccination was all shown to be cost-effective. Most studies (7/8) also showed that it was cost-effective to implement bivalent, quadrivalent, and nine-valent HPV vaccines in LMICs. However, one study concluded that it was not cost-effective to implement bivalent HPV vaccination in Thailand. CONCLUSION: In general, the implementation of bivalent, quadrivalent and nine-valent HPV vaccination for adolescent girls was cost-effective in both high-income countries and regions and low- and middle-income countries and regions in Asia. Policy makers in HICs could consider expanding the target vaccinated population, while for LMICs it is essential to reduce HPV vaccine price to a level at which the implementation of HPV vaccination is cost-effective.

The Seroprevalence of Dengue Virus Infection and Its Association With Iron (Fe) Level in Pregnant Women in Guangzhou, China.

Dengue fever is regarded as the most prevalent mosquito-borne viral disease in humans. However, information of dengue virus (DENV) infection in pregnant women and the influence factors remain unclear. In this study, we extracted information of 2,076 pregnant women from the Prenatal Environment and Offspring Health (PEOH) birth cohort conducted since 2016 in Guangzhou, China. Peripheral blood and clean midstream urine samples of participants were collected during their hospitalization for childbirth. Indirect enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) antibodies of DENV in serum samples, and inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the Fe concentrations in the urine samples, which were then adjusted for by urine creatinine and transformed by natural logarithm (ln-Fe). The seroprevalence of DENV IgG antibody in all included participants was 2.22% (46/2,076). We observed higher seroprevalence of IgG antibody in women aged ≥35 years (2.9%), education ≤ 12 years (2.5%), yearly income per capita <100,000 yuan (2.4%), no use of air-conditioner (2.4%), no use of mosquito coils (2.3%), and no exercise during pregnancy (4.1%). A U-shaped relationship was found between ln-Fe concentration and the risk of positive IgG antibody. Compared with women with ln-Fe concentration of 2.0-2.9 µg/g creatinine, slightly higher risks of positive IgG antibody were found among women with ≤2.0 (RR = 4.16, 95% CI: 0.78, 19.91), 3.0-3.9 (RR = 1.93, 95% CI: 0.65, 7.08), 4.0-4.9 (RR = 2.19, 95% CI: 0.65, 8.51), and ≥5.0 µg/g creatinine of ln-Fe (RR = 2.42, 95% CI: 0.46, 11.33). Our findings suggested that the seroprevalence of dengue IgG antibody in pregnant women was comparable to the general population in Guangzhou, China. The risk of DENV infection may be associated with maternal demographic characteristics and behaviors. Both maternal low and high Fe concentrations may be positively associated with the risk of DENV infection.

Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL-22 expression to regulate the MAPK signaling pathway.

The objective of the present study was to observe the therapeutic effect of paroxetine combined with fluorouracil on mice with colorectal cancer (CRC) complicated with depression and to explore its mechanism of action. Using chronic mild stress and xenograft tumor methods to model CRC complicated with depression, 60 BALB/c mice were randomly divided into control, tumor model, tumor depression model, tumor depression antidepressant, tumor depression chemotherapy and tumor depression antidepressant plus chemotherapeutic drug groups. Changes in mouse sucrose preference and forced swimming tests were tracked. Changes in tumor volume and weight were compared, the tumor inhibition rate was calculated, Ki-67 expression in tumor tissues was detected using immunohistochemistry and IL-22 levels in peripheral blood were detected using ELISAs. Additionally, protein expression levels of IL-22, Bcl-2, Bax, caspase-3, p38, phosphorylated (p)-p38, ERK, p-ERK, JNK and p-JNK in tumor tissue were detected using western blotting. Following treatment with paroxetine and chemotherapy drugs, the sucrose preference index was increased, autonomic behavior dysfunction was alleviated and tumor growth was significantly inhibited. Furthermore, the expression levels of Ki-67 and apoptosis-related proteins, Bax and caspase-3, increased in tumor tissues, anti-apoptosis protein Bcl2 expression levels decreased significantly, IL-22 levels in the blood and tumor tissues were reduced and p-p38, p-ERK and p-JNK proteins were significantly reduced. It was concluded that paroxetine combined with chemotherapy drugs improved depressive behavior and promoted the survival state in a mouse model of CRC and depression, possibly through inhibiting IL-22 expression to regulate the activity of the MAPK signaling pathway.

Antioxidant status and cytogenetic damage in hospital workers occupationally exposed to low dose ionizing radiation.

The aim of the present study was to assess the oxidative stress level and chromosomal damage induced by occupational exposure to low dose ionizing radiation (LDIR). Two hundred and eighteen hospital workers occupationally exposed to LDIR were included in this study, along with 118 healthy age- and gender-comparable controls. Occupational dosimetry records were collected over the last year and revealed that the accumulated annual dose for each hospital worker was below the permissible limit of the International Commission on Radiological Protection (ICRP). The individuals' oxidative and antioxidative status were determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. The effect of radiation on chromosomal integrity was measured by the frequency of micronuclei (MN) formation using the cytokinesis block technique. Our results showed that the activities of CuZn-SOD and CAT enzymes and MDA levels observed in the hospital workers were higher than those in the controls (p < 0.05). We did not find significant difference in GSH-Px enzyme activity between the two groups (p = 0.247). A higher frequency of MN was found in exposed groups than in the controls [3(1-5) ‰ versus 2(0.75-4) ‰; p<0.001]. The difference was significant for males (p = 0.012), but not females (p = 0.14). Multiple linear regression analysis showed differences in the oxidant activities and MN frequency between hospital workers and controls adjusted for age, gender, smoking status and drinking status. Correlation analysis indicated that the frequency of MN was positively associated with MDA levels (p < 0.05). Altogether, these results support the detrimental effects of chronic low dose radiation in humans, which involves the induction of oxidative stress and chromosomal damage.

ATAD2 predicts poor outcomes in patients with ovarian cancer and is a marker of proliferation.

The oncogene ATPase family AAA domain­â€‹containing protein 2 (ATAD2) has been demonstrated to promote malignancy in a number of different types of tumor; however, its expression and role in ovarian cancer (OC) remain unknown. In the present study, it was demonstrated that ATAD2 acts as both a marker and a driver of cell proliferation in OC. Immunohistochemistry (IHC) and bioinformatics analyses were used to evaluate ATAD2 expression in OC, and multi­omics integrated analyses were used to dissect which factor resulted in its upregulation. Multiplex IHC assay was used to reveal the specific expression of ATAD2 in proliferating OC cells. CRISPR­Cas9­mediated gene editing was performed to investigate the effect of ATAD2 deletion on OC proliferation. The results demonstrated that ATAD2 is elevated in primary OC tissues compared with the adjacent normal tissue and metastases from the stomach. Genetic copy number amplification is a primary cause resulting in upregulation of ATAD2, and this was most frequently observed in OC. High ATAD2 expression was associated with advanced progression and predicted an unfavorable prognosis. ATAD2 could be used to identify cases of OC with a high proliferation signature and could label proliferating cells in OC. CRISPR­Cas9­mediated ATAD2 deletion resulted in a significant decrease in both cell proliferation and colony formation ability. Mechanistically, ATAD2­knockdown resulted in deactivation of the mitogen­activated protein kinase (MAPK) pathways, particularly the JNK­MAPK pathway, resulting in suppression of proliferation. Collectively, the data from the present study demonstrated that the ATD2 gene was frequently amplified and protein expression levels were upregulated in OC. Therefore, ATAD2 may serve as an attractive diagnostic and prognostic OC marker, which may be used to identify patients with primary OC, whom are most likely to benefit from ATAD2 gene­targeted proliferation intervention therapies.

Preoperative anxiety in Chinese colorectal cancer patients: The role of social support, self-esteem and coping styles.

BACKGROUND: Relatively little is known about preoperative anxiety and its associated factors with colorectal cancer, which is one of the most prevalent cancers. We aimed to investigate preoperative anxiety and its associated social, psychological and coping factors based on the disclosure/nondisclosure of cancer diagnosis. METHODS: A cross-sectional study was conducted in consecutive colorectal cancer inpatients (N = 434), whose anxiety was assessed based on semi-structured interview, demographic-clinical variables, social support, self-esteem and coping styles (acceptance-resignation, confrontation, avoidance). Hierarchical regression analyses were conducted to explore the relationships between social, psychological, coping factors and preoperative anxiety. RESULTS: There was no significant difference in preoperative anxiety (χ2 = 1.031, p = .31) between the disclosure and nondisclosure groups. Social, psychological and coping factors together accounted for an additional variance of preoperative anxiety (disclosure: 22%; nondisclosure: 20.8%). Social support (ß = -0.17, p = .004), self-esteem (ß = -0.22, p = .001) and coping styles (acceptance-resignation: ß = 0.32, p < .001; confrontation: ß = 0.13, p = .06; avoidance: ß = -0.17, p = .04) were associated with preoperative anxiety in the nondisclosure group. For the disclosure group, acceptance-resignation was the only significantly associated factor of preoperative anxiety (ß = 0.37, p < .001). CONCLUSIONS: Coping styles, such as acceptance-resignation and confrontation, could aggravate preoperative anxiety. Avoidance, social support and self-esteem might be helpful in preventing preoperative anxiety. These findings highlight the importance of providing psychological interventions for cancer patients by integrating social support, self-esteem and coping styles when disclosing a cancer diagnosis.

Telephone-based reminiscence therapy for colorectal cancer patients undergoing postoperative chemotherapy complicated with depression: a three-arm randomised controlled trial.

BACKGROUND: Colorectal cancer patients undergoing postoperative chemotherapy often exhibit symptoms of depression that in turn may negatively affect outcome. The aim of this study was to assess the efficacy of telephone-based reminiscence therapy on the depression, anxiety, subjective well-being, and social support of colorectal cancer patients undergoing postoperative chemotherapy complicated with depression. METHODS: Patients were divided randomly into a control group (CON, n = 45), telephone support group (TS, n = 45), and telephone-based reminiscence therapy group (TBR, n = 45). Patients in TS and TBR groups received six 20-40-min telephone intervention sessions conducted weekly. Patients were assessed at baseline and at 6 weeks. The primary outcomes were changes on the Self-Rating Depression Scale (SDS) and Hamilton Depression Scale (HAMD), which were used to evaluate depression symptoms. Secondary outcomes were changes in Self-Rating Anxiety Scale (SAS), Hamilton Anxiety Scale (HAMA), Memorial University of Newfoundland Scale of Happiness (MUNSH), and Perceived Social Support Scale (PSSS) scores, which were used to evaluate anxiety symptoms, subjective well-being, and social support, respectively. RESULTS: After 6 weeks, SDS and HAMD scores were significantly lower than pre-intervention baseline in the TBR group but not in the CON and TS groups (P < 0.05). Both SAS and HAMA scores were significantly reduced in TBR and TS groups but not the CON group (P < 0.05) following intervention; however, there was no significant difference in post-intervention scores between TS and TBR groups (P > 0.05). Neither telephone support nor telephone-based reminiscence therapy improved subjective well-being or social support (P > 0.05). CONCLUSIONS: These findings suggest that telephone-based reminiscence therapy can reduce depression symptoms in colorectal cancer patients undergoing postoperative chemotherapy. Telephone-based reminiscence therapy may also improve anxiety, but no better than telephone support. Alternatively, telephone-based reminiscence therapy did not improve subjective well-being or social support. We suggest that clinicians provide appropriate telephone-based reminiscence therapy in long-term care institutions based on patient mental health status.

Improving the anticancer activity of platinum(iv) prodrugs using a dual-targeting strategy with a dichloroacetate axial ligand.

Four novel platinum(iv) complexes, characteristic of DCA/TFA and with chloride ions as axial ligands, were designed and synthesized. This type of platinum(iv) complexes 1a-2b exhibited significant cytotoxic activity, and the cytotoxicity of 1b was the greatest among these four complexes, which was 20.61 fold and 7.65 fold higher than that of cisplatin against HepG-2 and NCI-H460 cancer cells, respectively. The result from the apoptosis assay of 1b was consistent with the result from the cytotoxicity assay. In addition, complexes 1a and 1b induced cell cycle arrest at the S phase on HepG-2 cells. Taken together, our data showed that Pt(iv) complex 1b released the corresponding Pt(ii) complex and DCA, and induced apoptosis as well as disruption of the mitochondrial membrane potential, establishing Pt(iv) complex 1b as a potential dual-targeting anticancer agent.

A chicken liver cell line efficiently supports the replication of ALV-J possibly through its high level viral receptor and efficient protein expression system.

In this study, we identified a chicken liver cell line (LMH) which could strongly support the replication of ALV-J (Subgroup J of avian leukosis virus) with high viral titer. Notably, ALV-J was efficiently detected by ELISA in LMH cells 1 day before DF1 cells. In comparison with DF1 cells, LMH cells not only expressed higher levels of ALV-J receptor chNHE-1, but also possessed a more efficient protein expression system for foreign genes. Thus, LMH cells could be a novel tool to shorten the ALV-J eradication approach and accelerate studies on the pathogenesis and oncogenesis of ALV-J.

Natural Borneol Enhances Paclitaxel-Induced Apoptosis of ESCC Cells by Inactivation of the PI3K/AKT.

Paclitaxel (PTX) has been used in a variety of malignancies for inhibiting tumor development and improving survival. However, its clinical application is limited due to poor solubility, drug resistance, and gastrointestinal reactions. Natural borneol (NB), as a promoter, could help to improve drug absorption. Therefore, the aims of the present study were to investigate the ability of NB to synergize with PTX to induce human esophageal squamous cell carcinoma (ESCC) cells apoptosis and the underlying mechanism of synergistic effects. In this study, our findings showed that NB could effectively synergize with PTX to inhibit the survival of ESCC cells by inducing apoptosis. The molecular mechanism by western blotting elucidated that combination treatment with PTX and NB significantly activated apoptotic pathway by triggering upregulation of cleaved caspase-3 expression and downregulation of survivin and P-AKT expression. These results demonstrated that NB could strongly potentiate PTX-induced apoptosis in ESCC cells through suppressing PI3K/AKT pathway. Thus, the combination therapy with NB and PTX might be a promising treatment strategy for human esophageal cancer. PRACTICAL APPLICATION: Esophageal cancer is one of the most common cancers in the world. It has brought about a major public health problem. Many natural agents have been employed in the synergized treatments of esophageal cancer. This study provides a comprehensive way to investigate the ability of borneol to synergize with paclitaxel to induce human esophageal squamous cell carcinoma cells apoptosis and the underlying mechanism of synergistic effects. The research showed that the combination treatment with some natural agents might be a promising treatment strategy for human esophageal cancer.

JSH-23 prevents depressive-like behaviors in mice subjected to chronic mild stress: Effects on inflammation and antioxidant defense in the hippocampus.

Nuclear factor-kappa B (NF-κB), which is reported to play an important role in the pathogenesis of depression, also has a central role in the genesis and progression of inflammation. Here, we have targeted the nuclear translocation of NF-κB using 4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23) to elucidate its role in depression. We investigated the antidepressant-like effects of JSH-23 in the chronic mild stress (CMS) mouse model, which is a valid, reasonably reliable, and useful model of depression. The antidepressant-like effects of JSH-23 were evaluated using the sucrose preference test (SPT) and the forced swimming test (FST). We also assessed inflammatory markers [interleukin (IL)-6 and tumor necrosis factor-α (TNF-α)] and components of antioxidant defense [superoxide dismutase (SOD) and nuclear factor erythroid-2-related factor 2 (Nrf 2)] in the hippocampus. Fluoxetine, a classical antidepressant, was used in this study as a positive control. Administration of JSH-23 significantly prevented the decreased sucrose preference in the SPT and prevented the increased immobility time in the FST caused by CMS, but had no effect on locomotor activity. Expression of NF-κB p65 protein in the hippocampus was decreased, and elevated levels of IL-6 and TNF-α were reduced, after JSH-23 administration. In addition to its anti-inflammatory effect, JSH-23 treatment increased the expression of SOD and Nrf 2 in the hippocampus, suggesting that it strengthens antioxidant defense. The current study demonstrated that inhibiting the NF-κB signaling cascade using JSH-23 prevented depressive-like behaviors by decreasing inflammation and improving antioxidant defense in the hippocampus. We concluded that NF-κB activation plays an important role in the pathophysiology of depression and that targeting NF-κB signaling may provide a novel and effective therapy for depression. Additional preclinical studies and clinical trials are, however, needed to further elucidate the effects of this therapeutic strategy.

Trends and Associated Factors of Hypertension among Residents Aged ≥15 Years in Guangzhou, China, 2004-2013.

BACKGROUND: We aimed to describe the trends and associated factors of hypertension among residents aged ≥15 yr in Guangzhou, China. METHODS: Three standardized cross-sectional health surveys were conducted in 2004, 2009 and 2013 using a multi-stage cluster sampling method, and a total of 69128 qualified participants were included in the study. The data were obtained through physical health examination and questionnaire survey. RESULTS: The age-standardised prevalence of hypertension increased from 12.5% to 16.0% between 2004 and 2009 and declined from 16.0% to 14.0% between 2009 and 2013, and crude prevalence respectively was 14.6%, 19.1% and 18.8% in 2004, 2009 and 2013. The proportion of optimal blood pressure dropped from 51.1% to 33.2%, high-normal blood pressure increased from 20.1% to 28.9%, grade 1 hypertension and grade 2 or 3 hypertension increased from 11.5% to 13.6% and 3.9% to 5.8% between 2004 and 2013. The average age was significantly increased (P<0.001) from 42.8 to 47.5 yr, and the average body mass index slightly increased (P<0.001) from 22.4 to 23.0. Logistic regression analysis shows that higher age, male, higher body mass index, smoking and drinking alcohol were potential risk factors for hypertension. CONCLUSION: Both crude and age-standardized prevalence of hypertension were initially increased, but subsequently decreased in Guangzhou during 2004-2013. The optimal blood pressure population decreased significantly while the high-normal blood pressure population increased substantially during the survey period.

Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a meta-analysis of randomized controlled trials.

The aim of this study is to meta-analytically assess the efficacy and safety of adjunctive raloxifene for postmenopausal women with schizophrenia. Six studies with 440 patients, including 225 (51.14%) patients on raloxifene and 215 (48.86%) on placebo who completed 13.71 ± 5.09 weeks of treatment, were included in this study. Meta-analysis of Positive and Negative Syndrome Scale total scores and positive, negative, and general symptom scores [standard mean difference (SMD) -0.22 to -0.55, 95% confidence interval (CI) -1.01 to -0.02, p = 0.04-0.01; I 2 = 74-79%] revealed an advantage of adjunctive raloxifene treatment over placebo treatment. There was no significant difference regarding discontinuation rate [risk ratio (RR) = 1.38, p = 0.51] and adverse drug reactions (RR = 1.27, p = 0.57) between the two groups. This meta-analysis showed that adjunctive raloxifene appears to be efficacious and safe for postmenopausal women with schizophrenia. Moreover, raloxifene may be efficacious for patients with less severe symptoms. Future studies with a large sample size are needed to confirm these findings.

Adolescent escitalopram prevents the effects of maternal separation on depression- and anxiety-like behaviours and regulates the levels of inflammatory cytokines in adult male mice.

There is little research on the effects of adolescent administration of antidepressants on behavioural function and inflammation in early-life stressed adult mice. Using maternal separation (MS), a paradigm of early adversity, we investigated the effects of adolescent (PND 33-54) escitalopram (ES; 10mg/kg) exposure on depression- and anxiety-like behaviours and the levels of inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, and IL-10) in the ventral hippocampus (HPV), prefrontal cortex (PFC), and serum in adult (PND 61) male offspring mice. The results showed that MS has no effect on locomotor activity, but increased depression-like behaviours in the saccharin preference test and increased anxiety-like behaviours in the social preference and elevated plus maze tests. MS increased the levels of IL-1ß in the HPV, PFC, and serum, while decreasing the level of IL-10 in the HPV. Furthermore, adolescent ES treatment inhibited these depression- and anxiety-like behaviours, decreased the levels of IL-1ß, and increased the level of IL-10 in the HPV. The results also showed that there are no effects of chronic escitalopram administration on normal behaviour in control mice. Taken together, the current data provide experimental evidence that MS increases depression and anxiety levels in adult male offspring. Additionally, the findings support the idea that early pharmacological intervention with ES may be an effective treatment for reducing the behavioral abnormalities induced by early adversity and regulating the underlying inflammatory mechanisms involved.

Association between Genetic Polymorphisms of DNA Repair Genes and Chromosomal Damage for 1,3-Butadiene-Exposed Workers in a Matched Study in China.

The aim of the study was to examine the association between polymorphisms of DNA repair genes and chromosomal damage of 1,3-butadiene- (BD-) exposed workers. The study was conducted in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and a circulatory water workshop in China. Newly developed biomarkers (micronuclei, MNi; nucleoplasmic bridges, NPBs; nuclear buds, NBUDs) in the cytokinesis-blocked micronucleus (CBMN) cytome assay were adopted to detect chromosomal damage. PCR and PCR-restriction fragment length polymorphism (RFLP) are adopted to analyze polymorphisms of DNA repair genes, such as X-ray repair cross-complementing Group 1 (XRCC1), O6-methylguanine-DNA methyltransferase (MGMT), poly (adenosine diphosphate-ribose) polymerases (ADPRT), and apurinic/apyrimidinic endonucleases (APE1). The BD-exposed workers exhibited increased frequencies of MNi and NPBs when compared to subjects in the control group. The results also show that the BD-exposed workers carrying XRCC1 diplotypes TCGA-CCGG (4.25 ± 2.06 ‰) (FR = 2.10, 95% CI: 1.03-4.28) and TCGG-TCGA (5.80 ± 3.56 ‰) (FR = 2.75, 95% CI: 0.76-2.65) had statistically higher NBUD frequencies than those who carried diplotype TCGG-TCGG (1.89 ± 1.27 ‰). Our study suggests that polymorphisms of XRCC1 gene may influence chromosomal damage in BD-exposed workers.

Colorectal cancer: using blood samples and tumor tissue to detect K-ras mutations.

We performed a meta-analysis to assess whether blood can be substituted for tumor tissue in K-ras mutation testing. PubMed, EMBASE, MEDLINE, and BIOSIS databases were searched. Twenty-three studies including 1261 patients were included. The pooled overall sensitivity, specificity, and concordance rate were 0.69 (95% CI: 0.59-0.78), 0.96 (95% CI: 0.93-0.97), and 0.86 (95% CI: 0.82-0.89), respectively. Subgroup analysis indicated that plasma (sensitivity: 0.74; mutation rate: 0.34) exhibited superior sensitivity compared with serum (sensitivity: 0.45; mutation rate: 0.24). We conclude that blood is a suitable substitute for tumor tissue in K-ras mutation testing. K-ras mutation positivity in blood can be used to identify patients who should not receive EGFR monoclonal antibody therapy, but the absence of blood positivity does not necessarily imply negativity.

Induction of DNA damage and G2 cell cycle arrest by diepoxybutane through the activation of the Chk1-dependent pathway in mouse germ cells.

1,2:3,4-Diepoxybutane (DEB) is a major carcinogenic metabolite of 1,3-butadiene (BD), which has been shown to cause DNA strand breaks in cells through its potential genotoxicity. The adverse effect of DEB on male reproductive cells in response to DNA damage has not been thoroughly studied, and the related mechanism is yet to be elucidated. Using mouse spermatocyte-derived GC-2 cells, we demonstrated in the present study that DEB caused the proliferation inhibition and marked cell cycle arrest at the G2 phase but not apoptosis. DEB also induced DNA damage as evidenced by γ-H2AX expression, the comet assay, and the cytokinesis-block micronucleus assay. Meanwhile, DEB triggered the Chk1/Cdc25c/Cdc2 signal pathway, which could be abated in the presence of UCN-01 or Chk1 siRNA. GC-2 cells exposed to DEB experienced ROS generation and pretreatment of N-acetyl-l-cysteine, partly attenuated DEB-induced DNA damage, and G2 arrest. Furthermore, measurement of testicular cells showed an increased proportion of tetraploid cells in mice administrated with DEB, alongside the enhanced expression of p-Chk1. Also, the defective reproductive phenotypes, including reduced sperm motility, increased sperm malformation, and histological abnormality of testes, were observed. In conclusion, these results suggest DEB induces DNA damage and G2 cell cycle arrest by activating the Chk1-dependent pathway, while oxidative stress may be associated with eliciting toxicity in male reproductive cells.

The protective effect of autophagy on mouse spermatocyte derived cells exposure to 1800MHz radiofrequency electromagnetic radiation.

The increasing exposure to radiofrequency (RF) radiation emitted from mobile phone use has raised public concern regarding the biological effects of RF exposure on the male reproductive system. Autophagy contributes to maintaining intracellular homeostasis under environmental stress. To clarify whether RF exposure could induce autophagy in the spermatocyte, mouse spermatocyte-derived cells (GC-2) were exposed to 1800MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rate (SAR) values of 1w/kg, 2w/kg or 4w/kg for 24h, respectively. The results indicated that the expression of LC3-II increased in a dose- and time-dependent manner with RF exposure, and showed a significant change at the SAR value of 4w/kg. The autophagosome formation and the occurrence of autophagy were further confirmed by GFP-LC3 transient transfection assay and transmission electron microscopy (TEM) analysis. Furthermore, the conversion of LC3-I to LC3-II was enhanced by co-treatment with Chloroquine (CQ), indicating autophagic flux could be enhanced by RF exposure. Intracellular ROS levels significantly increased in a dose- and time-dependent manner after cells were exposed to RF. Pretreatment with anti-oxidative NAC obviously decreased the conversion of LC3-I to LC3-II and attenuated the degradation of p62 induced by RF exposure. Meanwhile, phosphorylated extracellular-signal-regulated kinase (ERK) significantly increased after RF exposure at the SAR value of 2w/kg and 4w/kg. Moreover, we observed that RF exposure did not increase the percentage of apoptotic cells, but inhibition of autophagy could increase the percentage of apoptotic cells. These findings suggested that autophagy flux could be enhanced by 1800MHz GSM exposure (4w/kg), which is mediated by ROS generation. Autophagy may play an important role in preventing cells from apoptotic cell death under RF exposure stress.