Platelets-to-serum Ca2+ ratio as a risk factor for postoperative cerebral vasospasm in surgically treated aneurysmal subarachnoid hemorrhage patients.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) generally requires surgical intervention to secure the aneurysm(s). Cerebral vasospasm (CVS) is a common complication of aSAH that occurs before and after a clipping or coiling procedure. However, we have limited options for the prevention or early detection of CVS by far. Although some biomarkers were studied regarding the purpose, some of which are rather complicated and actually hard to obtain. We conducted this study to investigate the potential correlations between the platelets-to-serum Ca2+ ratio (P/C) and the occurrence of postoperative CVS in aSAH patients. PATIENTS AND METHODS: We enrolled 262 patients in this retrospective study, clinical features and lab results were collected from an electronic medical record (EMR) system. The variables were consecutively analyzed in univariate and multivariate analyses; p-values < 0.05 were considered significant. The predictive values of several certain variables for CVS were further assessed through receiver operating characteristic (ROC) analysis. RESULTS: The prevalence of CVS in our study was 33.6%. Patients suffering from CVS had significantly increased P/C levels compared to those who did not (p = 0.045). Multivariate logistic analysis revealed that P/C was independently associated with postoperative CVS (p = 0.041). ROC curves demonstrated prominent interactions between P/C and clinical rankings, in terms of predicting postoperative CVS in aSAH patients. At a cutoff value of 112.53, patients with higher P/C levels in the early stage of aSAH were more likely to develop symptomatic CVS after aneurysm occlusion (p = 0.004). CONCLUSIONS: Among aSAH patients, a higher P/C at admission increases the risk of postoperative CVS events and, with easy access, it may serve as a novel predictor for the complication.

Delayed intracerebral hemorrhage after ventriculo-peritoneal shunt procedure: two case reports and a review of literature.

OBJECTIVE: Ventriculo-peritoneal shunt (VPS) is a commonly used procedure for treating hydrocephalus of various causes. Delayed intracerebral hemorrhage (DICH) is regarded as a very rare complication after VPS procedure, with mechanisms still indeterminate. We report two cases of this condition whereby we discuss the characteristics and potential explanations for it in a short review of literature. CASE REPORT: Two female patients, aged 49, 76 respectively, were admitted to our hospital for hydrocephalus in the year 2021 as ordinary participants among many other patients with the same diagnosis. Unforeseeably, what made them special was DICH situations occurred after regular VPS procedures. Luckily both of them responded well to subsequent conservative treatment with no deterioration and were discharged promisingly in the end. Surprisingly, both of the valve mechanisms in these two functioned properly so far even after the ominous DICH events. Quality of life also improved a lot for them, thus we could consider the VPS surgery successful as well as the later management of the unwanted hematomas, in other words, a full recovery from DICH. CONCLUSIONS: Only few cases or series of DICH were reported in the past decades and the mechanisms of it still lack a verdict. We intend to attribute physical vascular injury due to a closer contact between cerebral blood vessels and the VPS catheter for DICH in the younger patient, while degenerative changes of brain tissue might be the protagonist in the elder one. More discreetness should be expected in perioperative management of VPS patients, with still a long way to go to fully understand the mechanisms of DICH and prevent the complication in highest measure.

Muscle wasting, a neglected complication associated with physical dysfunction in elderly patients with rheumatoid arthritis: a cross-sectional observational study.

Objective: Little is known about muscle wasting in elderly patients with rheumatoid arthritis (RA). We examined muscle characteristics and their clinical significance in this group.Method: Consecutive RA patients were recruited and clinical data were collected. Muscle mass and distribution were assessed using bioelectric impedance analysis. Myopenia was defined as an appendicular skeletal muscle mass index (ASMI) ≤ 7.0 kg/m2 (men) and ≤ 5.7 kg/m2 (women).Results: Among the 643 RA patients recruited, 165 (25.7%) were elderly patients (age ≥ 60 years) with a mean age of 65.1 ± 4.5 years. Compared with young patients (age < 60 years), elderly RA patients had significantly higher Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) (median 3.4 vs 3.2), Health Assessment Questionnaire Disability Index (HAQ-DI) (0.38 vs 0.13), and modified total Sharp score (mTSS) (16 vs 9), and a higher proportion of myopenia (54.5% vs 41.4%; all p < 0.01). Elderly RA patients with myopenia (n = 90, 14.0%) had significantly higher DAS28-CRP (3.6 vs 3.0), HAQ-DI (0.50 vs 0.12), and mTSS (21 vs 7) than young RA patients without myopenia (n = 280, 43.5%; all p < 0.0083). Multivariate logistic and linear regression analyses showed that myopenia, high HAQ-DI, active smoking, hypertension, diabetes, and coronary atherosclerotic heart disease were the main relevant characteristics of elderly RA patients. Age positively correlated with HAQ-DI, and ASMI negatively correlated with HAQ-DI (both p < 0.01). Further mediation analysis showed that ASMI partially mediated the association between age and HAQ-DI.Conclusion: Our data reveal that half of elderly RA patients manifest myopenia which aggravates physical dysfunction as a mediator of age. Myopenia, a neglected complication in elderly RA patients, should be recognized and further investigated.

MiR-200b-5p inhibits proliferation of ovarian cancer cells by targeting ATAD2 and regulating PI3K/AKT signaling pathway.

OBJECTIVE: The purpose of this study was to investigate the influences of micro ribonucleic acid (miR)-200b-5p on proliferation and apoptosis of ovarian cancer (OC) cells, and to explore its correlations with the target gene ATPase family, AAA domain containing 2 (ATAD2), and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. MATERIALS AND METHODS: Human ovarian fibroblasts (HOFs) or human OC cell lines (A2780) were cultured in vitro, and then, A2780 cells were separately transfected with miR-200b mimics or miR-NC or cultured with ATAD2-specific inhibitor BAY-850. Thereafter, the expression levels of miR-200b and ATAD2 messenger RNA (mRNA) were measured via qRT-PCR, and the proliferative capacity of cells was detected by CCK-8 assay. Next, the cell apoptosis was determined by means of flow cytometry and one-step TUNEL assay. Finally, the targeted regulatory relationship between miR-200b and ATAD2 was examined using a Luciferase reporter assay system, and the protein expressions were detected through Western blot (WB) assay. RESULTS: It was found that the expression level of miR-200b was remarkably lower (p<0.05), while the mRNA expression level of ATAD2 was notably higher (p<0.05) in A2780 cells than those in HOFs. The transfection with miR-200b mimics markedly reduced the mRNA expression level of ATAD2 (p<0.05) and the proliferative capacity (p<0.05) and increased the apoptosis rate (p<0.05) of A2780 cells. Besides, it was detected via the Luciferase reporter assay system that miR-200b inhibited ATAD2. BAY-850 significantly decreased the expression level of ATAD2 protein (p<0.05) and the proliferative capacity (p<0.05) but improved the apoptosis rate (p<0.05) of cells. Moreover, both miR-200b mimics and BAY-850 could distinctly repress the protein expression levels of PI3K and p-Akt of the PI3K/Akt signaling pathway (p<0.05) and enhance the expression of suppressor gene p53 (p<0.05). CONCLUSIONS: MiR-200b-5p can inhibit the proliferation and promote the apoptosis of OC cells through targeted inhibition of ATAD2 expression and regulation of the PI3K/Akt signaling pathway.

Advances in SARS-CoV-2: a systematic review.

OBJECTIVE: In December 2019, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection broke out in Wuhan, China. However, we still lack a comprehensive understanding of this emerging virus. In this manuscript, we collected relevant articles and reviewed the characteristics about SARS-CoV-2. MATERIALS AND METHODS: We performed an online search on PubMed and Web of Science with the keywords COVID-19, 2019-nCoV and SARS-CoV-2, and summarized the epidemiology, virology, clinical features and treatments of SARS-CoV-2 infection. RESULTS: We retrieved 157 published papers about SARS-CoV-2 from January, 2020 to April, 2020. We found that SARS-CoV-2 was a kind of virus with low mortality rate and high infectivity. This virus can enter human cells through angiotensin-converting enzyme 2 (ACE2) in alveoli and activate immune response in human body. SARS-CoV-2 infection can be classified as asymptomatic, mild, common, severe, and critical. We summarized antiviral drugs against SARS-CoV-2, such as remdesivir, hydroxychloroquine and favipiravir. Because the vaccine of SARS-CoV-2 is developing, more clinical studies are needed to verify the safety and efficacy of these treatments. CONCLUSIONS: SARS-CoV-2 is a novel coronavirus that has caused a global pandemic. We should pay more attention to prevent SARS-CoV-2 and try to control it sooner.

MiR-221 affects proliferation and apoptosis of gastric cancer cells through targeting SOCS3.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-221 affects proliferation and apoptosis of gastric cancer cells through targeting SOCS3, by Q.-Y. Zhou, P.-L. Peng, Y.-H. Xu, published in Eur Rev Med Pharmacol Sci 2019; 23 (21): 9427-9435-DOI: 10.26355/eurrev_201911_19436-PMID: 31773681" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19436.

MiR-221 affects proliferation and apoptosis of gastric cancer cells through targeting SOCS3.

OBJECTIVE: The suppressors of cytokine signaling 3 (SOCS3) negatively regulates the JAK-STAT pathway. The bioinformatics analysis revealed a targeted binding site between miR-221 and the 3'-UTR of SOCS3 mRNA. This study investigated the role of miR-221 in the proliferation and apoptosis of gastric cancer cells. PATIENTS AND METHODS: The Dual-Luciferase reporter gene assay validated the target relationship between miR-221 and SOCS3. Gastric cancer tissues were collected and compared with adjacent tissues to detect the expression of miR-221 and SOCS3. The Kaplan-Meier method was used to analyze the survival rate between patients with high and low miR-221 expression. Human gastric cancer SGC7901 cells were cultured and divided into the miR-NC group and miR-221 inhibitor group, followed by an analysis of the expression of miR-221, SOCS3, p-JAK2 and p-STAT3, cell apoptosis, and proliferation. RESULTS: Compared with adjacent tissues, miR-221 expression was significantly increased in tumor tissues, and SCOS3 mRNA expression was decreased. Compared with those with lower miR-221 expression, the prognosis of patients with higher miR-221 expression was significantly worse. There was a targeted regulatory relationship between miR-221 and SOCS3 mRNA. Compared with GES-1 cells, miR-221 expression in gastric cancer MGC803 and SGC7901 was significantly increased, and the expression of SOCS3 mRNA and protein was significantly decreased. The transfection of miR-221 inhibitor significantly increased SOCS3 expression in gastric cancer SGC7901 cells, decreased p-JAK2, p-STAT3 protein expression, increased cell apoptosis, and decreased cell proliferation. CONCLUSIONS: Increased miR-221 expression and decreased SOCS3 expression are related to gastric cancer. MiR-221 regulates the proliferation and apoptosis of gastric cancer cells by regulating SOCS3 expression.

Study on the relationship between the expression of IGF-1 in umbilical cord blood and abnormal glucose metabolism during pregnancy.

OBJECTIVE: To explore the relationship between the expression of insulin-like growth factor-1 (IGF-1) in neonatal umbilical cord blood and abnormal glucose metabolism during pregnancy. PATIENTS AND METHODS: We have selected 63 cases of delivery randomly, term birth and maternal from January 2015 to January 2016 in our hospital, gestational diabetes mellitus for Group A, abnormal gestational glucose tolerance for Group B and normal for Group C with 21 cases in each group. The venous blood samples were collected from all the pregnant females 2 weeks before delivery, and the levels of HbA1c in serum were detected by Elisa method. During the delivery, the umbilical cord blood was collected and the levels of IGF-1 were measured by double site immune enzyme analysis. The neonatal weight was recorded and the correlation analysis was made in respect of the measurement results. RESULTS: The level of HbA1c in Group A was significantly higher than that in Group C (p < 0.05); IGF-1 level and neonatal weight of Group B were significantly higher than that of Group C (p < 0.05), IGF-1 has a significant correlation with neonatal weight in Group C, and HbA1c and IGF-1 were positively correlated (p < 0.05); IGF-1 was positively correlated with neonatal weight in Group A and Group B (p < 0.05). There was a significant positive correlation between the IGF-1 level of neonatal umbilical cord blood and the neonatal weight (p < 0.05). Also, the level of HbA1c was positively correlated with the level of IGF-1 in neonatal umbilical cord blood at the end of pregnancy (p < 0.05). CONCLUSIONS: The expression level of IGF-1 in the final stage of pregnant females can be detected to predict the expression level of IGF-1 in newborn infants and then the growth status of the fetus can be obtained.

The SUMO-specific protease SENP5 controls DNA damage response and promotes tumorigenesis in hepatocellular carcinoma.

OBJECTIVE: SUMOylation plays critical roles in a variety of physiological and pathological processes including tumorigenesis. SUMOylation is a reversible process which is mediated by the SENP (Sentrin/SUMO-specific protease) family to remove SUMO from conjugated substrates. SENP5 has been reported to play critical roles in the control of several cancers including breast cancer, osteosarcoma and oral squamous cell carcinoma. In this study, we uncovered a role of SENP5 in promoting tumorigenesis process in hepatocellular carcinoma (HCC) via regulating DNA damage response. MATERIALS AND METHODS: The mRNA and protein levels of SENP5 in 10 pairs of HCC samples were determined by Realtime PCR and Western blot, respectively. SiRNAs were used to silence the expression of SENP5 in HepG2 cells. Male BALB/c nude mice were used to determine the roles of SENP5 on tumorigenesis. In vivo SUMOylation assay was used to detect the SUMOylation of ATRIP. Immunoprecipitation (IP) was used to detect the interaction between SENP5 and ATRIP. RESULTS: We found that SENP5 was over-expressed in HCC samples and required for HCC cells proliferation both in vitro and in vivo. SENP5-depleted HepG2 cells exhibited hypersensitivity to IR and etoposide treatment with defective checkpoint activation including decreased activation of ATR and phosphorylation of ATR targets. At the molecular level, we found that SENP5 interacted with ATRIP and promoted ATRIP deSUMOylation. CONCLUSIONS: Overall, our data suggest that SENP5 is required for HCC cell growth and might be a promising drug target for HCC.

Supraglottic jet oxygenation and ventilation during colonoscopy under monitored anesthesia care: a controlled randomized clinical trial.

OBJECTIVE: Supraglottic jet oxygenation and ventilation may provide active pulse oxygenation and ventilation in patients with respiratory suppression. This randomized controlled clinical study was designed to determine the efficacy and safety of supraglottic jet oxygenation/ventilation during monitored anesthesia care (MAC) by intravenous (IV) infusion of propofol in patients undergoing colonoscopy. PATIENTS AND METHODS: Forty-nine adult patients receiving colonoscopy were randomly divided into two groups: the control group with passive oxygen supply from regular nasal cannula (N = 24) and the supraglottic jet oxygenation/ventilation (SJV) group with active pulse oxygen supply and ventilation using a manual jet ventilator (N = 25). MAC was induced and maintained by intravenous injection of propofol. HR, ECG, BP, SaO2 were continuously monitored during and 1 hour after the procedure. RESULTS: Demographic characteristics were similar in height, weight, age and BMI (Body Mass Index) between the two groups. Compared to the control group, the SJV group had similar averaged lowest SaO2, but highest SaO2 in SJV group were significantly lower during operation (p = 0.01). The proportion of maximum chest rise movement were increased significantly in SJV group (p = 0.03) compared with control group. Demographic characteristics were similar in the times needed to use facial mask ventilation, percentage of time to maintain SaO2 above 96%, average PetCO2 during the procedure, or complications between the two groups. CONCLUSIONS: SJV can provide adequate oxygenation/ventilation during monitored anesthesia care and convenient monitoring for patients' breath, without complications.

Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014.

With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22,774 and 84,572 annually. Rates of extended-spectrum ß-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.

Integrated regulatory network involving differently expressed genes and protein-protein interaction on pancreatic cancer.

OBJECTIVE: Pancreatic cancer is a deadly disease with poor prognosis. However, comprehensive understanding about its pathogenesis remains insufficient. In this study, we aimed to find potential novel approaches for the treatment of pancreatic cancer and explore the regulatory mechanisms underlying pancreatic cancer progression. MATERIALS AND METHODS: The gene expression profile data GSE32688 were downloaded from Gene Expression Omnibus database followed by background correction and normalization through GCRMA (GC Robust Multi-array Average) method. Then DEGs (differentially expressed genes) were identified using t-test method and DEGs-related PPIs (protein-protein interaction) were extracted from STRING database. The PPI networks were constructed by calculating the pearson correlation coefficient under different conditions. Moreover, the network was divided into a number of unit modules, and KEGG pathway and GO analysis were performed for genes in module networks using clusterProfiler. RESULTS: In total, 199 DEGs (165 up-regulated genes and 34 down-regulated genes) were screened between tumor and normal samples. The integrated DEG. PPI network was established by comparing two different networks under tumor and normal conditions respectively. The top ten genes with high degrees such as ANLN, PSRC1 and ECT2 were identified in the integrated network, and they were mainly enriched in cell cycle pathway. CONCLUSIONS: ECT2 and PSRC1 might be used as two novel biomarkers for diagnosis and management of pancreatic cancer.

Increased Angiogenesis and Decreased Programmed Cell Death Increases the Risk of Uterine Cervical Cancer.

INTRODUCTION: Cervical cancer is one of the most common female malignancies and leading cause for high mortality rate. In the present study we made an attempt to determine the extent of angiogenesis, apoptosis, accumulation of mutant p53 protein, cell proliferation rate in the uterine cervical cancer tissues. MATERIALS AND METHODS: Cervical cancer samples were obtained from patients and they were subjected to PCR analysis and immunocytochemistry. RESULTS: A total of 30 cervical cancer tissue samples were analyzed, by PCR, we found 25 collected cervical cancer samples showed HPV-16 and E6 positive. Further, we observed the increased CD34 expression was associated with HPV-16 and E6 positive cancer tissues when compared to the corresponding control tissues. This elevated level of CD34 confirms the increased extent of angiogenesis in cervical cancer tissues. Further by immunocytochemistry we have demonstrated that the rate of apoptosis is reduced, over expression of bcl-2, Ki 67 and thus increases rate of cell proliferation. DISCUSSION: Therefore, our data suggest that development of new anticancer or antiviral drugs could efficiently compromise the HPV-16 mediated angiogenesis and reduced apoptosis in cervical cancer and thus will improve the survival rate of patients.

USP14 inhibitor IU1 prevents ventilator-induced lung injury in rats.

The pathophysiology of ventilator-induced lung injury (VILI) involves multiple mechanisms including inflammation. USP14 removes the ubiquitin chain of I-κB, therefore inducing I-κB degradation and increasing cytokine release. The purpose of this study was to examine the protecting roles and mechanisms of USP14 inhibitor on I-κB expression and lung injury induced by high tidal volume ventilation in normal rat lung. Male Sprague-Dawley rats were divided into follows: Two ventilation modalities were used: rats in Groups LD (low volume + DMSO) and LI (low volume + IU1) received ventilation with a tidal volume of 8 ml/kg, while the rats in Groups HD (high volume + DMSO) and HI (high volume + IU1) were ventilated with a tidal volume of 40 ml/kg. The levels of lung wet-to-dry weight ratio were used as indicators of water metabolism in lung tissue; the detection of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid was used to indicate inflammatory response, while lung injury was assessed by injury score and morphological changes under light microscope. The USP14 and I-κB protein level was measured in lung tissue by Western blot. Our results indicated that administration of IU1 alleviated ventilator-induced lung injury which was accompanied by reduced MPO activity, wet-to-dry weight ratio, lower TNF-α, IL-1ß, IL-6 and IL-8 levels and increased I-κB expression in lung tissue. IU1 could significantly alleviate ventilator-induced rat lung injury by attenuate intrapulmonary inflammatory response.

Adenovirus mediated knockdown of bone morphogenetic protein 2 inhibits human lung cancer growth and invasion in vitro and in vivo.

Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-beta superfamily of signaling molecules, and has been shown to function as a tumor suppressor involved in development and progression of many malignancies. BMP-2 has previously been reported to be closely correlated with lung cancer. But, the role and molecular mechanisms of BMP-2 in lung cancer have not yet been comprehensively explained. The present study aims to elucidate the role of BMP-2 in growth and invasion of human lung adenocarcinoma (LAC) in vitro and in vivo. Adenovirus vector-mediated BMP-2 small hairpin RNA (shBMP-2) was used to transfect into A549 LAC cells to determine the functional relevance of BMP-2 and tumor growth and invasion in vitro and in vivo, and further investigate the expression levels of BMP-2, vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9), phosphatidylinositol 3-kinase p85alpha (PI3Kp85alpha) and phosphorylated AKT (p-AKT). As a result, LAC cell proliferation and invasion were significantly diminished by knockdown of BMP-2 indicated by MTT and Transwell assays, and cell apoptosis and cycle arrest were markedly induced indicated by flow cytometry. When BMP-2 expression was knocked down, the expression of PI3Kp85alpha, p-AKT, VEGF and MMP-9 was also down-regulated in LAC cells. In addition, the tumor volumes in LAC subcutaneous nude mouse model treated with shBMP-2 were significantly smaller than those in control and ad-GFP groups. Taken together, our findings indicate that knockdown of BMP-2 inhibits growth and invasion of LAC cells possibly via blockade of the PI3K/AKT signaling pathway, and BMP-2 may be a potential therapeutic target for lung cancer.

Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinson's disease.

Epidemiological studies have raised the possibility of caffeine serving as a neuroprotective agent in Parkinson's disease (PD). This possibility has gained support from findings that dopaminergic neuron toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or other neurotoxins is attenuated by co-administration of caffeine in mice. Here we examined the time window of caffeine's neuroprotection as well as the effects of caffeine's metabolites (theophylline and paraxanthine) in the MPTP mouse model of PD. In the first experiment, caffeine pre-treatment (30 mg/kg ip) significantly attenuated MPTP-induced striatal dopamine depletion when it was given 10 min, 30 min, 1 h, or 2 h but not 6 h before MPTP (40 mg/kg ip) treatment. Meanwhile, caffeine post-treatment also significantly attenuated striatal dopamine loss when it was given 10 min, 30 min, 1 h or 2 h but not 4 h, 8 h or 24 h after MPTP injection. In the second experiment, both theophylline (10 or 20 mg/kg) and paraxanthine (10 or 30 mg/kg) administration (10 min before MPTP) significantly attenuated MPTP-induced dopamine depletion in mice, as did caffeine (10 mg/kg) treatment. Thus the metabolites of caffeine also provide neuroprotective effects in this mouse model of PD. The data suggest that if caffeine protects against putative toxin-induced dopaminergic neuron injury in humans, then precise temporal pairing between caffeine and toxin exposures may not be critical because the duration of neuroprotection by caffeine may be extended by protective effects of its major metabolites.

Differential proteomic analysis of HeLa cells treated with Honokiol using a quantitative proteomic strategy.

Honokiol (HNK) is an active component purified from Magnolia officinalis. HNK exhibits antitumor effects by inducing apoptosis and inhibiting the growth of many cancer cell lines, while proteins involved in antitumor effects in proteomic level are still unclear. In our study, HNK could inhibit HeLa cell proliferation and induce apoptosis in a concentration- and time-dependent manner. We utilized a quantitative proteomic technique termed SILAC (Stable isotope labeling with amino acids in cell culture)-MS (mass spectrometry) to study the differential proteomic profiling of HeLa cells treated by HNK. A total of 85 proteins were changed after HeLa cells were treated with 12 microg/ml HNK for 8 h, and 8 proteins showed up-regulation while 77 proteins down-regulated. The changed proteins were classified into 9 different categories, which covered a broad variety of cellular functions. In conclusion, HNK performs cytotoxicity to HeLa cells through co-operating of many proteins and different pathways.

Impaired cutaneous wound healing in granulocyte/macrophage colony-stimulating factor knockout mice.

BACKGROUND: Wound healing involves various cells and cytokines, resulting in the regular progression of remodelling events. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a multifunctional pleiotropic cytokine and is known to facilitate wound healing, although the precise molecular and cellular mechanisms remain to be explored. OBJECTIVES: To use GM-CSF gene knockout (GM-CSF KO) mice to investigate the role of GM-CSF in cutaneous wound healing following full-thickness skin injury. METHODS: Full-thickness skin wounds were made in GM-CSF KO and wild-type mice. The wound closure, leucocyte infiltration, vascularization and extent of cytokine production were determined. RESULTS: Wound healing was significantly delayed in GM-CSF KO mice, accompanied by reduced cytokine production (interleukin-6, monocyte chemoattractant protein-1 and macrophage inflammatory protein-2), and platelet-endothelial cell adhesion molecule-1 expression. Consequently there was reduced recruitment of neutrophils and macrophages and reduced vascularization in the wounds of GM-CSF KO mice. Although collagen deposition was delayed, it was significantly increased in the wounds of the GM-CSF KO mice in the later stages of wound healing. CONCLUSIONS: We conclude that GM-CSF plays an important role in the complex network of effector molecules that regulate keratinocyte proliferation and the inflammatory response. These data have important implications for further development of the therapeutic manipulation of wound healing using GM-CSF.

Effectiveness of ganciclovir against human herpesvirus-6 excreted in saliva in stem cell transplant recipients.

The aim of this study was to evaluate the effect of ganciclovir on human herpesvirus-6 (HHV)-6. Forty allogeneic stem cell transplant recipients were prospectively studied by repeated sampling of the saliva. The saliva samples were assayed for HHV-6 by quantitative polymerase chain reaction. HHV-6 was detected in 33 patients. Ganciclovir was given as preemptive therapy for cytomegalovirus infection during 15 episodes that were compared to 18 episodes without any concomitant antiviral therapy. The mean HHV-6 load decreased 0.49 (s.e. 0.31) log(10)/week in patients receiving ganciclovir whereas it increased 0.15 (s.e. 0.17) log(10)/week in episodes without antiviral therapy (P=0.04). We conclude that ganciclovir can decrease the HHV-6 viral load in saliva.

Identification of a 98-kb DNA segment containing the rice Eui gene controlling uppermost internode elongation, and construction of a TAC transgene sublibrary.

The recessive 'tall rice' phenotype associated with the mutation eui (elongated upper-most internode) is an important agronomic trait that has been introduced into hybrid rice to eliminate panicle enclosure in all types of male-sterile lines and produce good-quality seeds in high yield and at low cost. Based on our previous Eui mapping data, we conducted fine-structure mapping and positional cloning of the gene using an F2 population comprising more than 5000 individuals derived from a cross of the near-isogenic lines 307T (eui/eui) with the recurrent parent Zhenshan 97 (Eui/Eui). In total 45 CAPS (cleaved amplified polymorphic sequences) markers located within an interval of 14.5 cM were analyzed in the subpopulation of 1298 homozygous recessive plants. The resulting high-resolution map defined a 98-kb interval containing the Eui locus flanked by the markers M0387 and M01, and three markers were found to co-segregate with Eui. In order to facilitate the identification of the Eui gene, we used a transformation-competent artificial chromosome (TAC) vector to construct a set of contiguous TAC clones from the Nipponbare BACs (obtained from the Clemson University Genome Institute; CUGI) spanning this region. These clones can be used to streamline complementation testing. The markers tightly linked to the Eui locus can also be used in breeding male-sterile lines with the elongated uppermost internode.