Deviatoric stress-induced metallization, layer reconstruction and collapse of van der Waals bonded zirconium disulfide.

In contrast to two-dimensional (2D) monolayer materials, van der Waals layered transition metal dichalcogenides exhibit rich polymorphism, making them promising candidates for novel superconductor, topological insulators and electrochemical catalysts. Here, we highlight the role of hydrostatic pressure on the evolution of electronic and crystal structures of layered ZrS2. Under deviatoric stress, our electrical experiments demonstrate a semiconductor-to-metal transition above 30.2 GPa, while quasi-hydrostatic compression postponed the metallization to 38.9 GPa. Both X-ray diffraction and Raman results reveal structural phase transitions different from those under hydrostatic pressure. Under deviatoric stress, ZrS2 rearranges the original ZrS6 octahedra into ZrS8 cuboids at 5.5 GPa, in which the unique cuboids coordination of Zr atoms is thermodynamically metastable. The structure collapses to a partially disordered phase at 17.4 GPa. These complex phase transitions present the importance of deviatoric stress on the highly tunable electronic properties of ZrS2 with possible implications for optoelectronic devices.

Decreased circulating omega-3 fatty acids increase the risk of myocardial infarction: a two-sample Mendelian randomization study.

Background: Many studies have shown that omega-3 fatty acids may play critical roles in cardiovascular diseases. Myocardial infarction (MI) typically results from a thrombotic occlusion of a coronary artery leading to myocardial ischemia. Thus, this study aims to examine the association between omega-3 fatty acids and MI. Methods: A two-sample Mendelian randomization study was used to explore the causal relationship between circulating omega-3 fatty acids and the risk of MI performed by MR-Egger regression, inverse-variance weighted (IVW), weighted median, and weighted mode. Results: Five single-nucleotide polymorphisms strongly related to circulating omega-3 fatty acids were selected as instrumental variables from a published genome-wide association study (GWAS) meta-analysis including 13,544 subjects. We extracted summary data for the risk of MI from another GWAS meta-analysis including 171,875 individuals (43,676 cases and 128,199 controls). The genetically predicted lower circulating omega-3 increased the risk of myocardial infarction showed by the results of IVW [odds ratio (OR) = 1.224, 95% CI = 1.045-1.433, P = 0.012], weighted median method (OR = 1.171, 95% CI = 1.042-1.315, P = 0.008), and weighted mode (OR = 1.149, 95% CI = 1.002-1.317, P = 0.117), although the result of MR-Egger was not significant (OR = 0.950, 95% CI = 0.513-1.760, P = 0.880) with a wider confidence interval. Conclusion: The findings from our Mendelian randomization analysis suggest that the association between omega-3 fatty acid levels and MI is likely causal.

Predictive value of atherogenic index of plasma and atherogenic index of plasma combined with low-density lipoprotein cholesterol for the risk of acute myocardial infarction.

Background and aims: Acute myocardial infarction (AMI) is a prevalent medical condition associated with significant morbidity and mortality rates. The principal underlying factor leading to myocardial infarction is atherosclerosis, with dyslipidemia being a key risk factor. Nonetheless, relying solely on a single lipid level is insufficient for accurately predicting the onset and progression of AMI. The present investigation aims to assess established clinical indicators in China, to identify practical, precise, and effective tools for predicting AMI. Methods: The study enrolled 267 patients diagnosed with acute myocardial infarction as the experimental group, while the control group consisted of 73 hospitalized patients with normal coronary angiography. The investigators collected general clinical data and relevant laboratory test results and computed the Atherogenic Index of Plasma (AIP) for each participant. Using acute myocardial infarction status as the dependent variable and controlling for confounding factors such as smoking history, fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), blood pressure at admission, and diabetes history, the researchers conducted multivariate logistic regression analysis with AIP as an independent variable. Receiver operating characteristic (ROC) curves were employed to determine the predictive value of AIP and AIP combined with LDL-C for acute myocardial infarction. Result: The results of the multivariate logistic regression analysis indicated that the AIP was an independent predictor of acute myocardial infarction. The optimal cut-off value for AIP to predict AMI was -0.06142, with a sensitivity of 81.3%, a specificity of 65.8%, and an area under the curve (AUC) of 0.801 (95% confidence interval [CI]: 0.743-0.859, P < 0.001). When AIP was combined with LDL-C, the best cut-off value for predicting acute myocardial infarction was 0.756107, with a sensitivity of 79%, a specificity of 74%, and an AUC of 0.819 (95% CI: 0.759-0.879, P < 0.001). Conclusions: The AIP is considered an autonomous determinant of risk for AMI. Utilizing the AIP index alone, as well as in conjunction with LDL-C, can serve as effective predictors of AMI.

Clinical significance of carotid intima-media thickness and plasma homocysteine in acute ST-segment elevation myocardial infarction.

Background: Patients with acute ST-segment elevation myocardial infarction (STEMI) often have fewer identifiable traditional risk factors compared to other types of acute coronary syndrome. Therefore, it is necessary to explore more sensitive predictive models different from traditional cardiovascular scoring systems to identify high-risk populations. The retrospective case-control study aimed to investigate the predictive value of carotid intima-media thickness (CIMT) and homocysteine (Hcy) on the occurrence of STEMI. Methods: A total of 198 patients with first STEMI were continuously selected into the observation group, who received emergency coronary angiography in Hefei Hospital Affiliated to Anhui Medical University from January 2020 to January 2022, and a total of 129 patients with chest pain and chest tightness who received coronary angiography to exclude significant coronary artery disease were selected as the control group in the above hospitals during the same period. Hcy was biochemical index determined by fasting blood sampling within 48 h after admission, while CIMT and carotid plaque was measured using ultrasound. Univariate and multivariate logistic regression analysis was used to screen out independent risk factors including Hcy, CIMT and carotid plaque of STEMI. On the basis of traditional risk factors, Hcy, CIMT and carotid plaque were introduced in order to form different combined diagnosis models. The receiver operating characteristic (ROC) curve of single indicator and multi-indicator combined diagnosis were plotted to evaluate the clinical usefulness of the study factors or diagnostic models. Based on those, a Nomogram was constructed to predict STEMI. Results: Hcy (OR =1.161, 95% CI: 1.084-1.244, P<0.001), CIMT (OR =206.968, 95% CI: 22.375-1,914.468, P<0.001), carotid plaque (OR =2.499, 95% CI: 1.214-5.142, P=0.013) were independent risk factors for STEMI (P<0.01). ROC results suggested that the area under the curve (AUC) of Hcy was 0.729, the optimal cut-off value was 13.525 µmol/L. The AUC of CIMT is 0.763, and the optimal cut-off value is 0.875mm. Combined with the independent predictors including smoking, diabetes, high density lipoprotein cholesterol, low density lipoprotein cholesterol, Hcy, CIMT, carotid plaque, the AUC of the diagnosis model was 0.892 (95% CI: 0.856-0.928, P<0.001). Based on the above results, a Nomogram for predicting STEMI was constructed with a C-index of 0.892. The results of the H-L fitting test show that χ2=1.5049, df=2, P=0.4712; the calibration curve of the Nomogram is close to the ideal curve, and the internal validation C-index was 0.880. The clinical decision curve analysis (DCA) shows that the "nomogram line" of the model is far from the "All line" and the "None line". Conclusions: Hcy, CIMT, and carotid artery plaque could be independent risk factors of STEMI. The inclusion of these factors in addition to traditional risk factors can more fully and accurately predict the risk of STEMI. The Nomogram based on the results of this study is feasible and can bring clinical net benefit.

SUN5 Interacting With Nesprin3 Plays an Essential Role in Sperm Head-to-Tail Linkage: Research on Sun5 Gene Knockout Mice.

Acephalic spermatozoa syndrome is a rare genetic and reproductive disease. Recent studies have shown that approximately 33-47% of patients with acephalic spermatozoa syndrome have SUN5 mutations, but the molecular mechanism underlying this phenomenon has not been elucidated. In this study, we generated Sun5 knockout mice and found that the head-to-tail linkage was broken in Sun5-/- mice, which was similar to human acephalic spermatozoa syndrome. Furthermore, ultrastructural imaging revealed that the head-tail coupling apparatus (HTCA) and the centrosome were distant from the nucleus at steps 9-10 during spermatid elongation. With the manchette disappearing at steps 13-14, the head and the tail segregated. To explore the molecular mechanism underlying this process, bioinformatic analysis was performed and showed that Sun5 may interact with Nesprin3. Further coimmunoprecipitation (Co-IP) and immunofluorescence assays confirmed that Sun5 and Nesprin3 were indeed bona fide interaction partners that formed the linker of the nucleoskeleton and cytoskeleton (LINC) complex participating in the connection of the head and tail of spermatozoa. Nesprin3 was located posterior and anterior to the nucleus during spermiogenesis in wild-type mice, whereas it lost its localization at the implantation fossa of the posterior region in Sun5-/- mice. Without correct localization of Nesprin3 at the nuclear membrane, the centrosome, which is the originator of the flagellum, was distant from the nucleus, which led to the separation of the head and tail. In addition, isobaric tag for relative and absolute quantitation results showed that 47 proteins were upregulated, and 56 proteins were downregulated, in the testis in Sun5-/- mice, and the downregulation of spermatogenesis-related proteins (Odf1 and Odf2) may also contribute to the damage to the spermatozoa head-to-tail linkage. Our findings suggested that Sun5 is essential for the localization of Nesprin3 at the posterior nuclear membrane, which plays an essential role in the sperm head-tail connection.

Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression.

OBJECTIVES: Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. METHODS: We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. RESULTS: First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. CONCLUSION: Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.

Corrigendum: A Novel wx2 Gene of Toxoplasma gondii Inhibits the Parasitic Invasion and Proliferation in vitro and Attenuates Virulence in vivo via Immune Response Modulation.

[This corrects the article DOI: 10.3389/fmicb.2020.00399.].

Association of ABCB1 C3435T Polymorphism with Echocardiographic Index Among Patients with Atherosclerotic Ischemic Stroke and Transient Ischemic Attack.

Emerging evidence has suggested that patients with ischemic stroke (IS) and/or transient ischemic attack (TIA) are more likely to exhibit myocardial disorders, which can be reflected by transthoracic echocardiography (TTE). ATP binding cassette transporter 1 (ABCB1) plays an important role in the development and progression of atherosclerotic pathology. The objective of the current study was to investigate the associations of ABCB1 C3435T polymorphism with echocardiographic performances among patients with acute ischemic stroke. Patients with IS or TIA, who were hospitalized and received TTE between October 2016 to March 2019, were enrolled in this study. Demographic data and echocardiographic parameters of each participant were recorded. We included 122 patients, with the respective distribution of 12.30%, 48.36%, and 39.34% in CC, CT, and TT genotypes. There were significant differences among the three ABCB1 types, with respect to RV (P = 0.036). The presence of the TT genotype was associated with increased MVE (OR = 0.13, P = 0.02) but correlated with decreased RV (OR = -1.46, P = 0.02). Our study indicated that ABCB1 C3435T polymorphism is associated with echocardiographic parameters among patients with acute ischemic stroke. The presence of the TT genotype is associated with diastolic function and cardiac hypertrophy.

A Novel wx2 Gene of Toxoplasma gondii Inhibits the Parasitic Invasion and Proliferation in vitro and Attenuates Virulence in vivo via Immune Response Modulation.

Toxoplasma gondii (T. gondii) is an obligate intracellular apicomplexan protozoan that can parasitize most warm-blooded animals and cause severe diseases in immunocompromised individuals or fetal abnormalities in pregnant woman. The treatment of toxoplamosis has been limited by effective drugs. Our previous work indicated that the novel gene wx2 of T. gondii may serve as a vaccine antigen candidate. To further investigate the molecular functions of wx2 in highly virulent T. gondii (RH strain), a wx2 gene deletion mutant RH strain (KO-wx2) was established using CRISPR-Cas9. The phynotype of KO-wx2 was analyzed by plaque, invasion, and replication assays in vitro as well as in vivo virulence assays. The results indicated that the targeted deletion of the wx2 gene significantly inhibited in vitro parasite growth and replication in the host cells as well as attenuated parasite virulence in the mouse model. Notably, the percentage of pro-inflammatory factors of interferon gamma (IFN-γ) and interlukin-17A (IL-17A) and anti-inflammatory factor of interlukin-10 (IL-10) in the lymph nodes were upregulated in mice infected with the KO-wx2 strain. Our data suggested that the wx2 gene plays an important role in the process of the parasite's life cycle and virulence in mice. In addition, it also plays an important role in the host's immunity reaction, mainly via Th1 and Th17 cellular immunity, not Th2.

Extracellular Vesicles (EVs) from Lung Adenocarcinoma Cells Promote Human Umbilical Vein Endothelial Cell (HUVEC) Angiogenesis through Yes Kinase-associated Protein (YAP) Transport.

Yes kinase-associated protein (YAP) plays an important role in angiogenesis and can promote the occurrence and development of many tumor types. However, whether YAP affects tumor angiogenesis in lung cancer, and its potential mechanism in lung cancer, are unknown. In this study, we explored the role of YAP in the angiogenesis of lung adenocarcinoma, and further illustrated its possible mechanism. The expression levels of YAP and the vascular endothelial marker protein CD31 were examined by immunohistochemistry and immunofluorescence in human lung adenocarcinoma tissues, revealing a possible positive correlation between YAP and CD31 in lung adenocarcinoma. The results of the western blotting (WB) of Human Umbilical Vein Endothelial Cells (HUVECs) after coculture with lung adenocarcinoma H1975 cells, H1975 cell-supernatants and H1975-derived EVs showed that YAP derived from H1975 cells can enter HUVECs via EVs. These results were confirmed by immunofluorescence. Finally, we generated H1975 low-YAP expression cells by transfecting the cells with a shYAP lentivirus, and confirmed that the low expression of YAP in H1975 cells inhibits HUVEC angiogenesis by reducing the amount of YAP that enters HUVECs. We found, for the first time, that YAP promotes angiogenesis in lung adenocarcinoma via EVs, at least partially. Our work may provide a promising method for lung cancer treatment by targeting angiogenesis in the future.

Efficient AuPd@GO-based electrochemical nanoprobe for sensitive detection of histone acetylase activity and its inhibitor.

Histone acetylase (HAT p300), which has aroused great concern in fundamental research and clinical applications, serves as one class of significant tumor markers. In our work, a sensitive electrochemical immunoassay for testing HAT p300 based on both graphene-assisted supported AuPd nanomaterial (AuPd@GO composite) and a typical amperometric i-t technique with fast response is developed favorably. The AuPd@GO-based sensing mechanisms are distributed as follows: the HAT p300 derived acetylation reaction occurs at the customized peptide-immobilized electrode; the AuPd@GO composite acts as carrier to immobilize acetyl antibody, thus constructing a sandwich-type electrochemical immunosensor via an antigen and antibody interaction; importantly, a distinct electrochemical signal could be caught due to the AuPd@GO nanomaterial with a favorable electrocatalytic property to the commercialized 3,3,5',5'-tetramethyl benzidine solution (TMB). Taking advantage of AuPd@GO composite, the established immunosensor displays a wide linear range from 1 pM to 1000 nM, and the detection limit is 0.5 pM (S/N = 3) for HAT p300. Next, the biosensor is also used to analyze the inhibitor of HAT p300 successfully, which is promising for promoting the development of electrochemical HAT-related biodetection and drug discovery. Graphical abstract A sensitive electrochemical immunoassay for testing HAT p300 based on both graphene-assisted supported AuPd nanomaterial (AuPd@GO composite) and a typical amperometric i-t technique with fast response is developed favorably.

Characterization of metallization and amorphization for GaP under different hydrostatic environments in diamond anvil cell up to 40.0 GPa.

High-pressure phase stability of gallium phosphide was explored under different hydrostatic environments up to 40.0 GPa in a diamond anvil cell. Two irreversible phase transitions from the semiconductor to metal to an amorphous state appear at 19.8 and 31.5 GPa and as well as 22.6 and 35.3 GPa under nonhydrostatic and hydrostatic environments, respectively. Furthermore, the hysteresis effect of the high-pressure phase transition of a sphalerite-structure compound under a hydrostatic environment was disclosed. All of the obtained results can provide new insight into the underlying structural evolution and electrical transport characteristics for the semiconducting compound at different hydrostatic environments.

SPAG4L/SPAG4Lß interacts with Nesprin2 to participate in the meiosis of spermatogenesis.

SUN domain proteins are identified as a novel family of nuclear envelope proteins which are involved in spermatogenesis. SPAG4L is identified as the fifth member of this family. Previous studies have revealed that SPAG4L is involved in spermatogenesis and the mutations occurring in SPAG4L will lead to male infertility. However, the transcriptions of SPAG4L and its interacting proteins in the testis are still unclear. In this study, we identified a shorter transcript variant of SPAG4L, named SPAG4Lß, in human testis by northern blot and reverse transcription-polymerase chain reaction. Bioinformatics analysis showed that it encodes a protein consisting of 311 amino acids, and subcellular localization analysis revealed that it is mainly expressed in the cytoplasm. In situ hybridization and immunofluorescence assay revealed that SPAG4L/SPAG4Lß is involved in meiosis. Furthermore, co-IP results demonstrated that SPAG4L/SPAG4Lß interacts with Nesprin2, a KASH domain protein to form the LINC (linker of nucleoskeleton and cytoskeleton) complexes. Immunofluorescence results revealed that the LINC complexes of Spag4l/Nesprin2 in mouse are involved in spermatocyte division. Our data indicated that SPAG4L/SPAG4Lß may play an important role in the meiotic process.

Phase Transition and Metallization of Orpiment by Raman Spectroscopy, Electrical Conductivity and Theoretical Calculation under High Pressure.

The structural, vibrational, and electronic characteristics in orpiment were performed in the diamond anvil cell (DAC), combined with a series of experimental and theoretical research, including Raman spectroscopy, impedance spectroscopy, atomic force microscopy (AFM), high-resolution transmission electron microscopy (HRTEM), and first-principles theoretical calculations. The isostructural phase transition at ~25.0 GPa was manifested as noticeable changes in the compressibility, bond lengths, and slope of the conductivity, as well as in a continuous change in the pressure dependence of the unit cell volume. Furthermore, a pressure-induced metallization occurred at ~42.0 GPa, accompanied by reversible electrical conductivity. We also determined the metallicity of orpiment at 45.0 GPa by first-principles theoretical calculations, and the results were in good agreement with the results of the temperature-dependent conductivity measurements. The HRTEM and AFM images of the recovered sample confirmed that orpiment remains in the crystalline phase with an intact layered structure and available crystal-shaped clusters. These high-pressure behaviors of orpiment present some crucial information on the structural phase transition, metallization, amorphization and superconductivity for the A2B3-type of engineering materials at high pressure.

Pressure-induced metallization in MoSe2 under different pressure conditions.

In this study, the vibrational and electrical transport properties of molybdenum diselenide were investigated under both non-hydrostatic and hydrostatic conditions up to ∼40.2 GPa using the diamond anvil cell in conjunction with Raman spectroscopy, electrical conductivity, high-resolution transmission electron microscopy, atomic force microscopy, and first-principles theoretical calculations. The results obtained indicated that the semiconductor-to-metal electronic phase transition of MoSe2 can be extrapolated by some characteristic parameters including abrupt changes in the full width at half maximum of Raman modes, electrical conductivity and calculated bandgap. Under the non-hydrostatic condition, metallization occurred at ∼26.1 GPa and it was irreversible. However, reversible metallization occurred at ∼29.4 GPa under the hydrostatic condition. In addition, the pressure-induced metallization reversibility of MoSe2 can be revealed by high-resolution transmission electron and atomic force microscopy of the recovered samples under different hydrostatic conditions. This discrepancy in the metallization phenomenon of MoSe2 in different hydrostatic environments was attributed to the mitigated interlayer van der Waals coupling and shear stress caused by the insertion of pressure medium into the layers.

[Functions of lamin B1 and the new progress of its roles in neurological diseases and tumors].

Lamin B1 is one of the essential members of the nuclear lamina protein family. Its main function is to maintain the integrity of nuclear skeleton, as well as to participate in the cell proliferation and aging by affecting the chromosome distribution. gene expression, and DNA damage repair. The abnormal expression of lamin B1 is related to certain diseases, including neurological diseases [e.g. neural tube defects (NDTs), adult-onset autosomal dominant leukodystrophy (ADLD)] and tumors (e.g. pancreatic cancer). It is also a potential tumor marker as well as drug target. Further research on lamin B1 will help people understand the molecular mechanism of the emergence and development of neural system diseases and tumors, and define a new future in drug target.

Neuropilin-1 (NRP-1) upregulated by IL-6/STAT3 signaling contributes to invasion in pancreatic neuroendocrine neoplasms.

Although the upregulation of Neuropilin-1 (NRP-1) is associated with many solid tumors, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The aim of this study was to investigate the role of NRP-1 in improving treatment and determining the prognosis of pNEN. In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analyzed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with small interfering RNAs against NRP-1 or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The expression of NRP-1 in pNEN tissues was markedly increased compared with adjacent normal pancreatic tissues. High NRP-1 expression was strongly correlated with tumor grades (P = .026), lymph node metastasis (P = .025), and tumor-node-metastasis stages (P = .012). Furthermore, NRP-1 downregulation notably inhibited the metastatic capacity of pNEN cells, and STAT3 knockdown was found to downregulate the expression of NRP-1. BON1 cells upregulated NRP-1 expression upon stimulation with IL-6. This was accompanied by activation/phosphorylation of the AKT and STAT3 signaling pathways. Western blot of extracts of human pNENs confirmed increased NRP-1 expression, as well as AKT/STAT3 phosphorylation in tissue of pNENs with elevated expression levels of IL-6. In conclusion, our findings suggest that NRP-1 is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with the IL-6/STAT3 signaling pathway.

Autotaxin upregulated by STAT3 activation contributes to invasion in pancreatic neuroendocrine neoplasms.

Although the upregulation of autotaxin (ATX) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The expression of ATX in pNEN tissues and pNEN cell line BON1 was analysed by Western blot, PCR and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with siRNAs against ATX or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The following results were obtained. The expression of ATX in pNEN tissues was significantly increased compared with that in normal pancreatic tissues. High ATX expression was strongly correlated with tumour grade, lymph node metastasis and tumour-node-metastasis stage. Furthermore, ATX downregulation notably inhibited the metastatic capacity of pNEN cells, whereas STAT3 knockdown was found to downregulate the expression of ATX. ATX expression was upregulated in BON1 cells upon stimulation with IL-6, and this was accompanied by activation/phosphorylation of STAT3. Western blot analysis of human pNEN tissue extracts confirmed increased ATX expression and STAT3 phosphorylation with elevated expression levels of IL-6. In conclusion, ATX is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with STAT3 activation.

Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis.

The aim of the present study was to investigate the protective effect of eugenol on the transplanted heart and explore its mechanisms of action. Male Sprague-Dawley rats were randomly divided into a sham group (n=10), a eugenol group (n=10 pairs, donors and recipients) and a control group (n=10 pairs, donors and recipients). The recipients in the eugenol group received an intraperitoneal injection of eugenol (20 mg/kg/day). The sham group and the control group received equal volumes of physiological saline by intraperitoneal injection. After 15 days the recipients in the control and eugenol groups underwent abdominal heterotopic heart transplantation, while the sham group received only a coeliotomy. The orthotopic hearts in the sham group and the heterotopic hearts in the eugenol and control groups, as well as the peripheral blood samples from all three groups were taken 3 h post operation for biochemical, histopathological, molecular and apoptosis analyses. Compared with the control group, the eugenol treatment significantly reduced the myocardial malondialdehyde content, serum cardiac troponin I, creatine kinase-MB, tumor necresis factor-α and interleukin-6 levels (P<0.05) and significantly alleviated myocardial injury. Western blot analysis demonstrated that the protein expression of cleaved Poly (ADP-ribose) polymerase 1, BAX and active caspase-3 in the eugenol group were significantly decreased, while B-cell lymphoma 2 expression was significantly increased compared with the control group (P<0.05). The myocardial apoptosis rate of the eugenol group was significantly decreased compared with the control group (P<0.05). In conclusion eugenol treatment significantly reduced myocardial injury and demonstrated protective effects for the transplanted heart.

HE4 expression in lung cancer, a meta-analysis.

BACKGROUND: The prognostic role of Human epididymis protein 4 (HE4) expression in lung cancer remains controversial. We performed this meta-analysis to assess the prognostic value of HE4 expression in lung cancer. METHODS: A systematic literature search was conducted to identify eligible studies in PubMed, Embase and Wanfang databases. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to assess the relationship. RESULTS: A total of 1412 patients from 8 studies were included in this meta-analysis. The results of univariate analysis (HR=1.73, 95% CI: 1.19-2.52, P=0.004) and multivariate analysis (HR=2.49, 95% CI: 1.89-3.28, P<0.001) demonstrated that high HE4 expression in lung cancer patients was correlated with poor overall survival (OS). We observed through further stratified analysis of the results of the univariate analysis that high HE4 expression was associated with worse OS in Asian lung cancer patients (HR=2.48, 95% CI: 1.88-3.26, P<0.001). However, there was no significant association between high HE4 expression and poor OS in Caucasian patients (HR=1.12, 95% CI: 0.80-1.55, P=0.513). CONCLUSION: High serum HE4 level was a marker of poor prognosis in lung cancer patients, particularly in Asian patients with lung cancer.