Associations between dietary antioxidant vitamins and risk of glioma: an updated systematic review and meta-analysis of observational studies.

Background: Epidemiological studies investigating the potential associations between antioxidant vitamins intake and risk of glioma have yielded inconsistent results. To address this, we carried out a systematic review and updated meta-analysis to explore the relationship between dietary antioxidant vitamins intake and risk of glioma. Methods: We comprehensively searched electronic databases including PubMed, Web of Science, Embase, Scopus, China National Knowledge Infrastructure (CNKI) and Wan fang Data from their inception to March 2024. We employed fixed-effects or random-effects models to estimate the pooled relative risks (RRs) and 95% confidence intervals (CIs) for the associations between dietary antioxidant vitamins intake and risk of glioma. Publication bias was assessed through the visual inspection of the funnel plots and quantified by the Begg's and Egger's tests. Heterogeneity across studies was assessed using the Cochran's Q test and I-square (I2). Additionally, subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and evaluate the robustness of the results. Results: Overall, a total of 15 articles involving 3,608 glioma cases and 771,930 participants were included in the final analysis. The pooled analyses revealed that the highest intake of vitamin C significantly reduced the risk of glioma (RR = 0.78; 95%CI: 0.63-0.96; P = 0.022), compared to the lowest intake. However, no significant associations were observed between vitamin A and vitamin E intake and the risk of glioma (P>0.05). Subgroup analyses revealed the inverse association between vitamin C intake and risk of glioma in the population-based case-control studies (RR = 0.82; 95%CI: 0.68-1.00, P = 0.049) and study quality <7(RR = 0.52, 95%CI: 0.29-0.92, P = 0.025). Conclusion: Our findings show that higher intake of vitamin C is strongly associated with a reduced risk of glioma, although a dose-response relationship was not evident. Future large-scale prospective studies are warranted to confirm these findings.

Folic acid protects against isoniazid-induced liver injury via the m6A RNA methylation of cytochrome P450 2E1 in mice.

Background: Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury. Methods: Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism. Results: FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1. Conclusion: FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.

Long non-coding RNA MM2P suppresses M1-polarized macrophages-mediated excessive inflammation to prevent sodium taurocholate-induced acute pancreatitis by blocking SHP2-mediated STAT3 dephosphorylation.

M1 macrophage-mediated excessive inflammatory response plays a key role in the onset and progression of acute pancreatitis (AP), and this study aimed to investigate the role and underlying mechanisms by which the macrophage polarization-related long noncoding RNA (lncRNA) MM2P participated in the regulation of AP progression. By performing quantitative reverse-transcription PCR (qRT-PCR) assay, lncRNA MM2P was found to be downregulated in both sodium taurocholate-induced AP model mice tissues and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and gain-of-function experiments confirmed that overexpression of lncRNA MM2P counteracted inflammatory responses, reduced macrophage infiltration and facilitated M1-to-M2 transformation of macrophages to ameliorate AP development in vitro and in vivo. Further mechanical experiments revealed that lncRNA MM2P inhibited Src homology 2 containing protein tyrosine phosphatase 2 (SHP2)-mediated signal transducer and activator of transcription 3 (STAT3) dephosphorylation to activate the STAT3 signaling, and silencing of SHP2 suppressed M1 type skewing in LPS-induced RAW264.7 cells. Interestingly, our rescuing experiments verified that lncRNA MM2P-induced suppressing effects on M1-polarization of LPS-treated RAW264.7 cells were abrogated by co-treating cells with STAT3 inhibitor stattic. Collectively, our data for the first time revealed that lncRNA MM2P suppressed M1-polarized macrophages to attenuate the progression of sodium taurocholate-induced AP, and lncRNA MM2P might be an ideal biomarker for AP diagnosis and treatment.

Perfluorooctane sulfonate and perfluorooctanoic acid inhibit progesterone-responsive capacitation through cAMP/PKA signaling pathway and induce DNA damage in human sperm.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two persistent organic pollutants harmful to human health. They induce negative effects on male reproduction by influencing male hormones, spermatogenesis, and sperm quality. However, their effects and mechanisms on human sperm capacitation and fertilization remain unclear. Here, human sperm were incubated with different concentrations of PFOS or PFOA with progesterone during capacitation. Both PFOS and PFOA inhibited human sperm hyperactivation, sperm acrosome reaction, and protein tyrosine phosphorylation levels. PFOS and PFOA decreased intracellular Ca2+ concentration in the presence of progesterone, and subsequently decreased cAMP level, and PKA activity. PFOS and PFOA increased reactive oxygen species production and sperm DNA fragmentation during the only 3 h capacitation incubation. Conclusively, PFOA and PFOS may inhibit human sperm capacitation via the Ca2+-mediated cAMP/PKA signaling pathway in the presence of progesterone, and induce sperm DNA damage through increased oxidative stress, which is not conducive to fertilization.

Lifestyle-related risk factors correlated with mental health problems: A longitudinal observational study among 686 male college students in Chongqing, China.

Aim: Public concerns over the mental health problems of college students are rising. Previous research show that female tend to suffer more from mental health problems than males, with few studies focusing on males. This study sought to explore the association of lifestyle-related risk factors with the prevalence of mental health problems among male college students in China. Methods: The lifestyle information and mental health status of 686 male college students from Chongqing, China, were assessed in 2014, and 582 of them were followed up a year later. Participants completed a questionnaire assessing demographic and lifestyle factors which include sleep quality, computer usage, sedentariness, physical activity, smoking, current alcohol, coke, coffee, and milk tea drinking, and current tea/fried food/baked food consumption. Mental health problems were measured using the Depression Anxiety Stress Scale-21 (DASS-21). Results: Univariate analyses indicated that age, sleep latency, sleep duration, computer usage time, milk tea drinking, and fried food consumption were potential risk factors for mental health problems (p's < 0.05). Multivariate analysis further revealed that, either at baseline or during follow-up, participants with (i) more computer usage time were at a higher risk of having depression symptoms (p's < 0.05) and (ii) a higher frequency of fried food consumption were associated with a higher risk of having depression, anxiety, and stress symptoms (p's < 0.05). Additionally, the cross-lagged analysis showed that (i) computer usage time in 2014 is positively correlated with depression status (ß = 0.106, p < 0.05) but not anxiety (ß = 0.047, p > 0.05) and stress (ß = 0.019, p > 0.05) status a year later and (ii) fried food consumption in 2014 is positively correlated with depression (ß = 0.129, p < 0.01), anxiety (ß = 0.168, p < 0.001), and stress (ß = 0.113, p < 0.01) status a year later. Conclusions: Computer usage time and fried food consumption were lifestyle-related risk factors for mental health problems in male college students in Chongqing, China. These results might emphasize further preventive strategies for mental health problems, especially in male college students.

FYN regulates cell adhesion at the blood-testis barrier and the apical ectoplasmic specialization via its effect on Arp3 in the mouse testis.

FYN is a non-receptor tyrosine kinase of the SRC family that facilitates virus entry across epithelial tight junctions. However, the role of FYN in mammalian testes in maintaining the blood-testis barrier (BTB) integrity and the adhesion of germ cells to Sertoli cells are not well defined. Here, we show that FYN is a component of the BTB and the apical ectoplasmic specialization (ES) at Sertoli-Sertoli and Sertoli-spermatid interfaces, respectively, and is expressed extensively in mouse testes during postnatal development. FYN was shown to be structurally linked to the actin and microtubule-based cytoskeletons. An in vivo model was used to explore the modulatory effect of FYN on BTB and apical ES dynamics within the testes when adult mice were treated intraperitoneally with CdCl2 (3 mg/kg body weight). The CdCl2-induced epithelial restructuring was associated with a transient increase in the interaction between FYN and the actin branching/nucleation protein Arp3, as well as an induction of Arp3 phosphorylation, which possibly lead to actin cytoskeleton remodeling, resulting in BTB damage and germ cell loss in the seminiferous epithelium. Based on the results, we propose a model in which FYN and Arp3 form a protein complex that is responsible for junction reorganization events at the apical ES and the BTB. It is also possible for viruses to break through the BTB and enter the immunoprivileged testicular microenvironment via this mechanism.

Epidemiologic Correlation and Drug Resistance Analysis of Pathogenic Bacteria in Different Open Limb Injury External Conditions.

OBJECTIVE: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. METHODS: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05. RESULTS: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. CONCLUSION: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.

Differential Size Distribution and Estrogen Receptor Cargo of Oviductal Extracellular Vesicles at Various Stages of Estrous Cycle in Mice.

Oviductal extracellular vesicles (OEVs) play an important role in fertilization and embryo development. However, it remains largely unknown whether the size and protein cargo of OEVs change during the estrous cycle in mice. This study analyzed the changes in the size distribution and protein cargo of OEVs at four stages of the estrous cycle in mice. The distribution widths of OEVs according to the estrous cycle stage were as follows: proestrus, 20-690 nm in diameter, with two peaks at 50 and 250 nm; estrus, 22-420 nm in diameter, with two peaks at 40 and 200 nm; metestrus, 30-70 nm diameter, with a single peak at 40 nm; and diestrus, 10-26 nm diameter, with a single peak at 20 nm. The estrogen receptor (ER) level in OEVs at the proestrus stage differed significantly from that at estrus (P = 0.013) and diestrus (P = 0.005). The levels of CD9 and Hsc70 fluctuated across the four stages, although with no significant differences. Furthermore, OEVs were observed among the cilia and microvilli of epithelial cells at the proestrus, estrus, and diestrus stages, but not at the metestrus stage. The number of observed OEVs was the highest at the proestrus stage, followed by the estrus, and the diestrus stage. Endosomes were also observed at the estrus and diestrus stages. The change of the OEV size and ER cargo is associated with the estrous cycle in mice. Our findings increase the understanding of the physiological characteristics of OEVs, which may have clinical applications.

Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by Helicobacter pylori-induced activator protein-1 promotes gastric tumorigenesis via the PI3K/AKT/mTOR pathway.

BACKGROUND: Gastric cancer (GC) is a common malignant tumor with high incidence and mortality rates globally, especially in East Asian countries. Helicobacter pylori (H. pylori) infection is a significant and independent risk factor for GC. However, its underlying mechanism of action is not fully understood. Dickkopf-related protein (DKK) 1 is a Wnt signaling antagonist, and cytoskeleton-associated protein (CKAP) 4 is a newly identified DKK1 receptor. Recent studies found that the binding of DKK1 to CAKP4 mediated the procancer signaling of DKK1 inde-pendent of Wnt signaling. We hypothesize that H. pylori-induced activation of DKK1/CKAP4 signaling contributes to the initiation and progression of GC. AIM: To investigate the interaction of H. pylori infection, DKK1 and CAKP4 in GC, as well as the underlying molecular mechanisms. METHODS: RNA sequencing was used to identify differentially expressed genes (DEGs) between H. pylori-infected and uninfected primary GC cells. Gain- and loss-of-function experiments were performed to verify the H. pylori-induced upregulation of activator protein-1 (AP-1) in GC cells. A dual-luciferase reporter assay and co-immunoprecipitation were used to determine the binding of AP-1 to the DKK1 promoter and DKK1 to CKAP4. Western blotting and immunohistochemistry detected the expression of DKK1, CKAP4, and phos-phatidylinositol 3-kinase (PI3K) pathway-related proteins in GC cells and tissues. Functional experiments and tumorigenicity in nude mice detected malignant behavior of GC cells in vitro and in vivo. RESULTS: We identified 32 DEGs between primary GC cells with and without H. pylori infection, including JUN, fos-like antigen-1 (FOSL1), and DKK1, and confirmed that the three proteins and CKAP4 were highly expressed in H. pylori-infected GC cells, H. pylori-infected gerbil gastric tissues, and human GC tissues. JUN and FOSL1 form AP-1 to transcriptionally activate DKK1 expression by binding to the DKK1 promoter. Activated DKK1 bound to CKAP4, but not the most common Wnt coreceptor low-density lipoprotein receptor-related protein 5/6, to promote GC cell growth, colony formation, migration, invasion, and xenograft tumor growth in nude mice. All these effects were driven by activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. Targeting the PI3K signaling pathway by LY294002 inhibited DKK1-mediated CKAP4/PI3K signaling activity and the malignant behavior of GC cells. CONCLUSION: H. pylori induces JUN and FOSL1 expression to form AP-1, which transcriptionally activates DKK1. Binding of DKK1 to KAKP4 contributes to gastric tumorigenesis via the PI3K/AKT/mTOR pathway.

Hsp90 modulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways.

BACKGROUND: Heat shock protein 90 (Hsp90) is a highly abundant eukaryotic molecular chaperone that plays important roles in client protein maturation, protein folding and degradation, and signal transduction. Previously, we found that both Hsp90 and its co-chaperone cell division cycle protein 37 (Cdc37) were expressed in human sperm. Hsp90 is known to be involved in human sperm capacitation via unknown underlying mechanism(s). As Cdc37 was a kinase-specific co-chaperone of Hsp90, Hsp90 may regulate human sperm capacitation via other kinases. It has been reported that two major mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase 1/2 (Erk1/2) and p38, are expressed in human sperm in the same locations as Hsp90 and Cdc37. Phosphorylated Erk1/2 has been shown to promote sperm hyperactivated motility and acrosome reaction, while phosphorylated p38 inhibits sperm motility. Therefore, in this study we explored whether Hsp90 modulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways. METHODS: Human sperm was treated with the Hsp90-specific inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) during capacitation. Computer-assisted sperm analyzer (CASA) was used to detect sperm motility and hyperactivation. The sperm acrosome reaction was analyzed by using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (PSA-FITC) staining. The interactions between Hsp90, Cdc37, Erk1/2 and p38 were assessed using co-immunoprecipitation (Co-IP) experiments. Western blotting analysis was used to evaluate the levels of protein expression and phosphorylation. RESULTS: Human sperm hyperactivation and acrosome reaction were inhibited by 17-AAG, suggesting that Hsp90 is involved in human sperm capacitation. In addition, Co-IP experiments revealed that 17-AAG reduced the interaction between Hsp90 and Cdc37, leading to the dissociation of Erk1/2 from the Hsp90-Cdc37 protein complex. Western blotting analysis revealed that levels of Erk1/2 and its phosphorylated form were subsequently decreased. Decreasing of Hsp90-Cdc37 complex also affected the interaction between Hsp90 and p38. Nevertheless, p38 dissociated from the Hsp90 protein complex and was activated by autophosphorylation. CONCLUSIONS: Taken together, our findings indicate that Hsp90 is involved in human sperm hyperactivation and acrosome reaction. In particular, Hsp90 and its co-chaperone Cdc37 form a protein complex with Erk1/2 and p38 to regulate their kinase activity. These results suggest that Hsp90 regulates human sperm capacitation via the Erk1/2 and p38 MAPK signaling pathways.

Hsp90 interacts with Cdc37, is phosphorylated by PKA/PKC, and regulates Src phosphorylation in human sperm capacitation.

BACKGROUND: Heat shock protein 90 (Hsp90) signaling pathways participate in protein phosphorylation during sperm capacitation. However, the underlying mechanism is largely unknown. OBJECTIVE: The aim of this study was to explore the interaction between Hsp90 and its co-chaperone protein, cell division cycle protein Cdc37 (Cdc37), in human spermatozoa. MATERIALS AND METHODS: We examined the effects of H-89 (a protein kinase A [PKA] inhibitor) and Go6983 (a protein kinase C [PKC] inhibitor) on the phosphorylation of serine, threonine, and tyrosine residues in Hsp90; the effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG, Hsp90 inhibitor) on Y416-Src phosphorylation; and the effects of 17-AAG and geldanamycin on threonine phosphorylation during human sperm capacitation. RESULTS: Hsp90 co-localized and interacted with Cdc37. During human sperm capacitation, Hsp90 phosphorylation at serine, threonine, and tyrosine residues was inhibited by H-89 and Go6983. In addition, phosphorylation of residue Y416 in the tyrosine kinase Src (its active site) was inhibited by 17-AAG, and the threonine phosphorylation levels of some proteins were decreased by 17-AAG and geldanamycin. DISCUSSION AND CONCLUSION: Taken together, our data showed that the interaction of Hsp90 with Cdc37 regulates total protein threonine phosphorylation and Src phosphorylation via its serine, threonine, and tyrosine phosphorylation, which are controlled by PKA and PKC during human sperm capacitation. The results of this study help understand the mechanism underlying Hsp90 regulation of sperm function.

Tranexamic Acid Inhibits Angiogenesis and Melanogenesis in Vitro by Targeting VEGF Receptors.

Melasma is a common but complex skin condition concerning cosmetic problems. Tranexamic acid (TA) has been proved to be effective in treatment of melasma with still unclear mechanisms. Here, we show that VEGF165 enhanced the expression of VEGF receptors (VEGFRs, including VEGFR-1, VEGFR-2 and NRP-1) in human umbilical vein endothelial cells (HUVECs), which was attenuated by TA. VEGF165 also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in HUVECs, which was again abolished by TA. TA further showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting cell proliferation, migration, invasion and tube formation of HUVECs induced by VEGF165, suggesting that TA could inhibit angiogenesis by targeting VEGFRs in HUVECs. In addition, VEGF165 enhanced the expression of VEGFRs and promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2 in normal human melanocytes, which were also attenuated by TA. Furthermore, TA showed similar effects to neutralization of VEGFR-1 and VEGFR-2 in inhibiting tyrosinase activity, melanin production and even melanogenic proteins induced by VEGF165, suggesting that TA could reduce melanogenesis via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that TA can inhibit angiogenesis and melanogenesis in vitro at least in part by targeting VEGFRs, which may offer a new understanding of the pathogenesis of melasma as well as the molecular mechanism for TA in treatment of the disease.

Effect of deoxynivalenol on the porcine acquired immune response and potential remediation by a novel modified HSCAS adsorbent.

The objective of this study was to determine the immunotoxic effects of deoxynivalenol (DON) in weaning piglets, and potential efficacy of a modified hydrated sodium calcium aluminosilicate (HSCAS) adsorbent to reduce DON toxicity. Four groups of 21-day-old male piglets (n = 7/group) were fed a control diet or diet containing 1.0 or 3.0 mg DON/kg, or 3.0 mg DON/kg plus 0.05% modified HSCAS for 4 weeks. Compared to the control, the DON diets decreased serum porcine circovirus antibody titer and the dermal hypersensitivity response to OVA at day 21 or 28. DON also induced focal necrosis and proliferation of cortical lymphocytes and apoptosis and increased the total antioxidant capacity and reduced glutathione, protein carbonyl concentrations in thymus. DON increased thymus mRNA, protein and (or) enzyme levels, cytokines (IL-6, IL-10, and TNF-α) and apoptosis-related genes (Caspase-3), while hematopoietic cell kinase (HCK) decreased. Intriguingly, the modified HSCAS alleviated the DON-induced changes on serum antibody titer, and thymic histopathology, apoptosis, redox status, inflammation and apoptosis signaling. In conclusion, these findings help to explain the toxic effects and mechanisms of DON and demonstrated the modified HSCAS adsorbent could be used to reduce the toxicity of DON in weaning piglets.

Activation of VEGF receptors in response to UVB promotes cell proliferation and melanogenesis of normal human melanocytes.

VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and signaling via VEGFRs extends beyond the classical roles in blood vessel formation. We previously showed VEGFRs were also expressed in epidermal keratinocytes and activation of VEGFR-2 by ultraviolet B (UVB) was involved in the pro-survival mechanism. Here, we show that both VEGF165 and UVB enhanced the expression of VEGFRs (including VEGFR-1, VEGFR-2 and NRP-1) in normal human melanocytes, and increased expression of VEGFRs by UVB was mediated through hypoxia and oxidative stress. Also, VEGF165 and UVB promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2, and UVB-induced phosphorylation of VEGFR-1 and VEGFR-2 required PKA but not P38 MAPK. In addition, UVB and VEGF165 contributed to the over-expression of melanogenic proteins in melanocytes, which could be reduced by neutralization of VEGFR-1 and/or VEGFR-2. UVB, but not VEGF165 promoted cell proliferation, while neutralization of VEGFR-1 and/or VEGFR-2 abolished this effect. UVB showed stronger than VEGF165 in promoting tyrosinase activity and melanin production, while neutralization of VEGFR-2 was stronger in reducing these effects than that of VEGFR-1. Furthermore, tranexamic acid (TA) decreased tyrosinase activity and melanin production via inhibiting activation of VEGFRs and subsequent expression of melanogenic proteins in melanocytes. Taken together, we demonstrate that VEGFRs are functionally involved in UVB-induced melanogenesis, and TA can inhibit melanogenesis at least in part by targeting VEGFRs in melanocytes.

The response of glandular gastric transcriptome to T-2 toxin in chicks.

This study was conducted to determine the effect of T-2 toxin on the transcriptome of the glandular stomach in chicks using RNA-sequencing (RNA-Seq). Four groups of 1-day-old Cobb male broilers (n = 4 cages/group, 6 chicks/cage) were fed a corn-soybean-based diet (control) and control supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. The histological results showed that dietary supplementation of T-2 toxin at 3.0 and 6.0 mg/kg induced glandular gastric injury including serious inflammation, increased inflammatory cells, mucosal edema, and necrosis and desquamation of the epithelial cells in the glandular stomach of chicks. RNA-Seq analysis revealed that there were 671, 1393, and 1394 genes displayed ≥2 (P < 0.05) differential expression in the dietary supplemental T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, compared with the control group. Notably, 204 differently expressed genes had shared similar changes among these three doses of T-2 toxin. GO and KEGG pathway analysis results showed that many genes involved in oxidation-reduction process, inflammation, wound healing/bleeding, and apoptosis/carcinogenesis were affected by T-2 toxin exposure. In conclusion, this study systematically elucidated toxic mechanisms of T-2 toxin on the glandular stomach, which might provide novel ideas to prevent adverse effects of T-2 toxin in chicks.

Selenium Deficiency Aggravates Aflatoxin B1-Induced Immunotoxicity in Chick Spleen by Regulating 6 Selenoprotein Genes and Redox/Inflammation/Apoptotic Signaling.

BACKGROUND: Selenium (Se) plays a protective role in aflatoxin B1 (AFB1)-induced splenic immunotoxicity in chicks. OBJECTIVE: This study was designed to reveal the underlying mechanism of Se-mediated protection against AFB1-induced splenic injury in broilers. METHODS: Four groups of 1-d-old Cobb male broilers (n = 5 cages/diet, 6 chicks/cage) were arranged in a 3-wk 2 × 2 factorial design trial whereby they were fed an Se-deficient, corn- and soy-based diet [base diet (BD), 36 µg Se/kg], BD plus 1.0 mg AFB1/kg, BD plus 0.3 mg Se/kg, or BD plus 1.0 mg AFB1/kg and 0.3 mg Se/kg (as 2-hydroxy-4-methylselenobutanoic acid). Serum and spleen were collected at week 3 to assay for cytokines, histology, redox status, selected inflammation- and apoptosis-related genes and proteins, and the selenogenome. RESULTS: Dietary AFB1 induced growth retardation and spleen injury, decreasing (P < 0.05) body weight gain, feed intake, feed conversion efficiency, and serum interleukin-1ß by 17.8-98.1% and increasing (P < 0.05) the spleen index and serum interleukin-6 by 37.6-113%. It also reduced the splenic lymphocyte number, the white pulp region, and histiocyte proliferation in Se-adequate groups. However, Se deficiency aggravated (P < 0.05) these AFB1-induced alterations by 16.2-103%. Moreover, Se deficiency decreased (P < 0.05) splenic glutathione peroxidase (GPX) activity and glutathione-S transferase and glutathione concentrations by 35.6-89.4% in AFB1-exposed groups. Furthermore, Se deficiency upregulated (P < 0.05) the apoptotic (Caspase 3 and Caspase 9) and antimicrobial (ß defensin 1 and 2) genes, but downregulated (P < 0.05) antiapoptotic (B-cell lymphoma 2) and inflammatory (E3 ubiquitin-protein ligase CBL-B) genes at the mRNA and/or protein level in AFB1 supplementation groups. Additionally, Se deficiency downregulated (P < 0.05) GPX3, thioredoxin reductase 1 (TXNRD 1), GPX4, and selenoprotein (SELENO) S, and upregulated (P < 0.05) SELENOT and SELENOU in spleen in AFB1 administered groups. CONCLUSIONS: Dietary Se deficiency exacerbated AFB1-induced spleen injury in chicks, partially through the regulation of oxidative stress, inflammatory and apoptotic signaling, and 6 selenoproteins.

Comparison of interleukin-6, interleukin-10, procalcitonin and C-reactive protein in identifying high-risk febrile illness in pediatric cancer patients: A prospective observational study.

The aim of this study is to systematically compare the performance of C-reactive protein (CRP), procalcitonin (PCT) and serum cytokines in identifying pediatric cancer patients with high-risk infection. A prospective observational study was performed from January 2014 through December 2016. Consecutive pediatric cancer patients who experienced febrile illness during hospitalization were enrolled. The CRP, PCT, interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were determined within 6 h of fever onset. A total of 3118 episodes of febrile illness were included, with 13.1% episodes documented as bloodstream infection (BSI) and 3.5% diagnosed as septic shock. Patients with BSI presented much higher levels of PCT, IL-6, IL-10 and TNF-α than patients with other types of fever and have much higher incidence of septic shock (11.2% vs. 2.3%, P < 0.001). IL-6 and IL-10 showed better performance in identifying patients with gram-negative bacteremia (GNB) and septic shock than CRP and PCT, respectively. The area under the curve (AUCs) of receiver operating characteristic (ROC) curve for septic shock prediction were 0.65, 0.78, 0.89 and 0.87 for CRP, PCT, IL-6 and IL-10, respectively. Furthermore, elevation of IL-6 and IL-10 were strongly associated with the development of GNB and septic shock. Our results indicate that BSI, especially GNB, is a high-risk form of infection which results in high incidence of septic shock. IL-6 and IL-10 performance better than CRP and PCT in identifying patients with high-risk febrile illness.

Emerging role for SRC family kinases in junction dynamics during spermatogenesis.

SRC family kinases (SFKs) are known regulators of multiple cellular events, including cell movement, differentiation, proliferation, survival and apoptosis. SFKs are expressed virtually by all mammalian cells. They are non-receptor protein kinases that phosphorylate a variety of cellular proteins on tyrosine, leading to the activation of protein targets in response to environmental stimuli. Among SFKs, SRC, YES and FYN are the ubiquitously expressed and best studied members. In fact, SRC, the prototypical SFK, was the first tyrosine kinase identified in mammalian cells. Studies have shown that SFKs are regulators of cell junctions, and function in endocytosis and membrane trafficking to regulate junction restructuring events. Herein, we briefly summarize the recent findings in the field regarding the role of SFKs in the testis in regulating spermatogenesis, particularly in Sertoli-Sertoli and Sertoli-germ cell adhesion. While it is almost 50 years since the identification of the oncogene v-Src encoded by Rous sarcoma transforming virus, the understanding of SFK involvement during spermatogenesis in the testis remains far behind that in other epithelia and tissues. The goal of this review is to bridge this gap.

Synthesis, structure and photoluminescence properties of a three-dimensional cadmium(II) (4,5)-connected coordination network.

The assembly of coordination polymers from metal ions and organic moieties is currently attracting considerable attention in crystal engineering due to their intriguing architectures and potential applications as functional materials. A new coordination polymer, namely poly[[µ2-trans-1,2-bis(pyridin-3-yl)ethylene-κ2N:N']bis(µ4-4,4'-oxydibenzoato-κ6O:O,O':O'':O'',O''')dicadmium(II)], [Cd2(C14H8O5)2(C12H10N2)]n or [Cd2(4,4'-OBB)2(3,3'-BPE)]n, has been synthesized by the the self-assembly of Cd(NO3)2·4H2O, 4,4'-oxydibenzoic acid (4,4'-H2OBB) and trans-1,2-bis(pyridin-3-yl)ethene (3,3'-BPE) under hydrothermal conditions. The title compound was structurally characterized by IR spectroscopy, elemental analysis and single-crystal X-ray diffraction analysis. Each CdII centre is coordinated by six carboxylate O atoms from four different 4,4'-OBB2- ligands and by one pyridyl N atom form a 3,3'-BPE ligand. Adjacent crystallographically equivalent CdII ions are bridged by 4,4'-OBB2- ligands, affording a two-dimensional [Cd(4,4'-OBB)]n net extending in the ac plane. Neighbouring [Cd(4,4'-OBB)]n nets are interlinked by 3,3'-BPE along the b axis to form a three-dimensional (3D) [Cd2(4,4'-OBB)2(3,3'-BPE)]n coordination network. In the network, each CdII centre is linked by four different 4,4'-OBB2- ligands and one 3,3'-BPE ligand. Meanwhile, each 4,4'-OBB2- ligand connects four separate CdII ions. Therefore, if the 4,4'-OBB2- ligands and CdII ions are considered as 4- and 5-connecting nodes, the structure of the title compound can be simplified as a 3D (4,5)-connected binodal framework with the rare (4462)(4466) TCS topology (Pearson, 1985; Blake et al., 2011). The thermal stability and photoluminescence properties of the title compound have also been investigated.

Substituent effects of two isophthalate derivatives on the construction of cadmium coordination polymers incorporating a dipyridyl ligand.

In recent years, the design and construction of crystalline coordination complexes by the assembly of metal ions with multitopic ligands have attracted considerable attention because of the unique architectures and potential applications of these compounds. Two new coordination polymers, namely poly[[µ-trans-1-(2-aminopyridin-3-yl)-2-(pyridin-4-yl)ethene-κ2N:N'](µ3-5-methylisophthalato-κ4O1,O1':O3:O3')cadmium(II)], [Cd(C9H6O4)(C12H11N3)]n or [Cd(5-Me-ip)(2-NH2-3,4-bpe)]n, (I), and poly[[µ-trans-1-(2-aminopyridin-3-yl)-2-(pyridin-4-yl)ethene-κ2N:N'](µ2-5-hydroxyisophthalato-κ4O1,O1':O3:O5)cadmium(II)], [Cd(C8H4O5)(C12H11N3)]n or [Cd(5-HO-ip)(2-NH2-3,4-bpe)]n, (II), have been prepared hydrothermally by the self-assembly of Cd(NO3)2·4H2O and trans-1-(2-aminopyridin-3-yl)-2-(pyridin-4-yl)ethene (2-NH2-3,4-bpe) with two similar dicarboxylic acids, i.e. 5-methylisophthalic acid (5-Me-H2ip) and 5-hydroxyisophthalic acid (5-HO-H2ip). The coordination network of (I) is a two-dimensional sql net parallel to (101). Adjacent sql nets are further linked to form a three-dimensional supramolecular framework via hydrogen-bonding interactions. Compound (II) is a two-dimensional (3,5)-connected coordination network parallel to (010) with the point symbol (63)(55647). As the other reactants and reaction conditions are the same, the structural differences between (I) and (II) are undoubtedly determined by the different substituent groups in the 5-position of isophthalic acid. Both (I) and (II) exhibit good thermal stabilities and photoluminescence properties.