Hemorrhagic Fever with Renal Syndrome Complicated by Acute Pancreatitis, High Intraocular Pressure, and Pulmonary Involvement: a Case Report.

Hemorrhagic fever with renal syndrome (HFRS), a naturally occurring epidemic disease, is primarily caused by hantaviruses. It frequently involves the lungs and is characterized by symptoms such as fever, hemorrhage, and renal failure. However, the occurrence of acute pancreatitis (AP) in HFRS patients can be neglected, and high intraocular pressure (IOP) is exceedingly uncommon. In this report, we discuss the case of a 30-year-old male who presented with fever, nausea, vomiting, and abdominal pain. Physical examination revealed extremity petechiae rashes and elevated IOP. Laboratory tests indicated coagulopathy and renal failure. A computed tomography scan confirmed AP. Further testing revealed a positive anti-hantavirus IgM antibody. The patient received supportive care, fluid hydration, hemofiltration, mannitol, brinzolamide, and brimonidine to reduce IOP. Three days post-admission, the patient developed shortness of breath and chest pain. Subsequent chest computed tomography revealed pulmonary edema and bilateral pleural effusion. Treatment included oxygen supply, respiratory support, and thoracentesis, with continued hemofiltration. The patient recovered, regaining normal pulmonary and renal functions and normalized IOP. This case underscores the importance of comprehensive evaluations and vigilant monitoring in HFRS patients, particularly measuring IOP in those with visual complaints, to save lives and reduce morbidity.

Lonicera flos and Curcuma longa L. extracts improve growth performance, antioxidant capacity and immune response in broiler chickens.

Alternatives to antibiotics are urgently needed to maintain broiler growth and health. The present study was conducted to evaluate the effects of Lonicera flos and Curcuma longa L. extracts (LCE) as antibiotic substitutes on growth performance, antioxidant capacity and immune response in broilers. A total of 480 one-day-old female broilers (WOD168) were allocated to 3 treatments with 5 replicates of 32 birds for 35 days. The 3 treatments were: an antibiotic-free basal diet (control, CON), CON +50 mg/kg spectinomycin hydrochloride and 25 mg/kg lincomycin hydrochloride (ANT), CON +500 mg/kg LCE (LCE). During the entire experimental period, supplementation of ANT and LCE increased (p < 0.01) average daily gain (ADG) and decreased (p < 0.05) feed conversion ratio (FCR), thereby resulting in greater final body weight (BW) compared with CON. Dietary LCE supplementation increased (p < 0.05) serum (glutathione peroxidase) GSH-Px, (superoxide dismutase) SOD and total antioxidant capacity (T-AOC) activities, and decreased (p < 0.05) serum malonaldehyde (MDA) concentration at day 35 compared with CON. There was no significant difference in serum catalase (CAT) activity among treatments. Birds in LCE group had lower (p < 0.05) MDA concentration and higher SOD activity in liver than those in CON and ANT groups at day 35. Birds in LCE group had higher (p < 0.05) phagocytic index and serum antibody titers to Newcastle disease virus (NDV) than those in CON group. Lower (p < 0.05) concentrations of pro-inflammatory cytokines and higher (p < 0.05) concentrations of anti-inflammatory cytokines in serum and liver were observed in birds fed LCE diet than those fed CON diet. In conclusion, dietary supplementation of LCE improved growth performance by enhancing antioxidant capacity, strengthening immune system and alleviating inflammation, which has potential as antibiotic alternatives.

TG2 as a novel breast cancer prognostic marker promotes cell proliferation and glycolysis by activating the MEK/ERK/LDH pathway.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor among women worldwide. Tissue transglutaminase 2 (TG2) has been reported as a major player across several types of cancer. However, the effects of TG2 in breast cancer are less known. METHODS: The expression of TG2 in patients with BC was detected by immunochemistry staining and RT-qPCR. The correlation of TG2 expression and clinicopathological factors or overall survival (OS) was analyzed by Chi-square test, Kaplan-Meier, and Cox-regression analysis. The effects of TG2 on cell proliferation and glycolysis were investigated in vivo and in vitro by gain- and loss-of-function experiments. RESULT: Both mRNA and protein levels of TG2 were overexpressed in BC tissues and cultured cells. Clinical stage (p = 0.011), molecular subtype (p<0.001) and survival status (p<0.001) were significantly correlated with TG2 expression. Specifically, TG2 expression was positively associated with the clinical stage (r = 0.193, p = 0.005) and OS (r = 0.230, p = 0.001), while negatively associated with molecular subtype (r = - 0.161, p = 0.020). Overexpressed TG2 was a prognostic factor of poor OS by Cox-regression analysis. Gain- and loss-of-function experiments indicated that cell proliferation and glycolysis were regulated by TG2 via the MEK/ERK/LDH pathway. TG2-induced activation of the MEK/ERK/LDH pathway and glycolysis were attenuated by MEK inhibitor U0126. CONCLUSION: TG2 is overexpressed in BC, which can serve as an independent prognostic factor for OS. TG2 promotes tumor cell proliferation and increases glycolysis associated with the activation of the MEK/ERK/LHD pathway.

D-serine and NMDA Receptor 1 Expression in Patients with Intractable Epilepsy.

AIM: To investigate the expression patterns of D-serine and N-methyl-D-aspartate (NMDA) receptor 1 in the temporal lobes of patients with intractable epilepsy. MATERIAL AND METHODS: Cortical temporal lobe brain tissue samples were collected from 20 patients with intractable epilepsy and 6 patients with brain trauma. The expression patterns of D-serine and NMDA receptor 1 were detected by immunofluorescence staining and western blot analysis. RESULTS: A total of 20 patients (11 males, 9 females) were included in the present study. D-serine expression was significantly higher in the neurons and glial cells of patients with intractable epilepsy than in control individuals. The mean integrated optical density (IOD) value for the intractable epilepsy group (13.37 ± 1.88) was significantly higher than that for the control group (9.27 ± 0.62, p < 0.05). The mean absorbance value of the NMDA receptor 1 protein strip obtained from intractable epileptic patients was 0.4175 ± 0.2321, which was significantly higher than the value of 0.2402 ± 0.1458 for the control group (p < 0.05). CONCLUSION: D-serine and NMDA receptor 1 expressions increased significantly in patients with intractable epilepsy compared with control patients. Therefore, the D-serine signaling pathway may represent a potential neurochemical target for epilepsy treatment.

Advances in Understanding CREB Signaling-Mediated Regulation of the Pathogenesis and Progression of Epilepsy.

Recent studies have indicated that the transcription factor cyclic adenosine monophosphate response element binding protein (CREB) is involved in the etiology of epilepsy. With regard to its transcriptional regulation, CREB phosphorylation is critical for the transmission of multiple extracellular signals, which implicates the activation of downstream target genes in the pathogenesis and progression of epilepsy. This review mainly focuses on recent discoveries of associations between the molecular and structural characteristics of CREB as well as the related CREB signaling pathway and epilepsy.

Structural characterization and in vitro-in vivo evaluation of effect of a polysaccharide from Sanguisorba officinalis on acute kidney injury.

We report here an acidic polysaccharide, namely RSP-3, which ameliorates acute kidney injury and is obtained from Sanguisorba officinalis. We extracted and purified two polysaccharides from this herb based on the acidity and screened them for their effect in regulating the immunological activity of macrophages. Among them, RSP-3 exhibited significant anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated macrophages by decreasing TNF-α and IL-6 levels. Subsequently, we found that RSP-3 suppressed ER stress, reduced ROS production and blocked NF-κBp65 translocation. After fully characterizing RSP-3 with a series of analytical technologies, we tested its anti-acute kidney injury (AKI) effect in vivo. In a murine AKI model induced by LPS, treatment with RSP-3 effectively ameliorated renal function. Besides, it decreased the levels of TNF-α and IL-6 in serum and reduced macrophage infiltration in injured kidney tissue. In sum, RSP-3, with a significant protective effect against AKI by showing anti-inflammatory activity, may become a meaningful drug candidate for treatment of AKI.

Performance of Serum Glypican 3 in Diagnosis of Hepatocellular Carcinoma: A meta-analysis.

INTRODUCTION AND AIM: Serum glypican-3 (GPC3) has been explored as a non-invasive biomarker of hepatocellular carcinoma (HCC). However, controversy remains on its diagnostic accuracy. Therefore, we aimed to conduct a systematic review and metaanalysis to evaluate the differential diagnostic accuracy of serum GPC3 between HCC and liver cirrhosis (LC) cases. MATERIAL AND METHODS: After the strict filtering and screening of studies from NCBI, PUBMED, Clinical Trials, Cochrane library, Embase, Prospero and Web of Science databases, 11 studies were selected. All studies provided the sensitivity and specificity of GPC3 and the alpha-fetoprotein (AFP) in the HCC and LC diagnosis. The sensitivity and specificity, and the area under the receiver operating characteristic curve (AUC) were determined and compared between GPC3 and AFP, which was set as a positive control. RESULTS: Pooled sensitivity (95% CI) and specificity (95% CI) were 0.55 (0.52-0.58) and 0.58 (0.54-0.61) for GPC3, 0.54 (0.51-0.57) and 0.83 (0.80-0.85) for AFP, and 0.85 (0.81-0.89) and 0.79 (0.73-0.84) for GPC3 + AFP, respectively. The AUCs of GPC3, AFP and GPC3 + AfP were 0.7793, 0.7867 and 0.9366, respectively. GPC3 had a nearly similar sensitivity as AFP, while the specificity and AUC of GPC3 was lower than that of AFP. The combination of GPC3 and AFP yielded a better sensitivity and AUC than GPC3 or AFP. CONCLUSION: Serum GPC3 is inferior to AFP in the differential diagnosis between HCC and LC. However, the combination of GPC3 and AFP exhibited a much better performance.

Immunohistochemical analysis of matrix metalloproteinase-9 predicts papillary thyroid carcinoma prognosis.

The present study aimed to explore the association between immunohistochemical matrix metalloproteinase-9 (MMP-9) expression and the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC), and to determine whether it may be used as a diagnostic or prognostic tool for PTC. Immunohistochemical staining of MMP-9 was performed in thyroid tissues obtained from 112 patients with PTC and 42 subjects with benign thyroid nodules (BTNs). The receiver operating characteristic curve was used to evaluate the legitimacy of MMP-9 as a diagnostic tool for PTC, and a predictor for structurally persistent/recurrent disease (SPRD) and disease status. Cox regression was applied to identify the risk factors of disease status and SPRD. The present study revealed that MMP-9 was overexpressed in PTC tissues, compared with in BTN tissues. Furthermore, MMP-9 scores yielded an area under the curve (AUC) of 0.842 (95% CI, 0.776-0.908) for differentially diagnosing PTC from BTN. In addition, the MMP-9 score was greater if patients previously had central lymph node metastasis, lateral lymph node metastasis or an advanced tumor-node-metastasis stage (III+IV). When MMP-9 was employed to predict disease status and SPRD, an AUC of 0.811 (95% CI, 0.706-0.917) and 0.806 (95% CI, 0.620-0.992) was obtained, respectively. A tumor size of >2 cm and an MMP-9 staining score of ≥6 were independent risk factors for predicting disease status, whereas vascular invasion and an MMP-9 staining score of ≥8 were risk factors for predicting SPRD. Furthermore, an MMP-9 staining score of ≥6 and ≥8 indicated shortened disease-free survival and survival without SPRD, respectively. In conclusion, the assessment of MMP-9 expression in thyroid carcinoma samples may represent a potential and supplementary tool for the diagnosis and prognostic prediction of PTC.

Predictive Significance of Serum MMP-9 in Papillary Thyroid Carcinoma.

OBJECTIVE: The incidence of papillary thyroid carcinoma (PTC) is increasing, and there are no reliable serum biomarkers for the diagnosis and prognosis of PTC. This study aimed to assess whether serum matrix metalloproteinase-9 (MMP-9) could serve as an auxiliary diagnostic/prognostic marker for PTC after total and partial thyroidectomy. MATERIAL AND METHODS: Postoperative serum MMP-9 concentrations were measured in 182 male patients with PTC, 86 male patients with benign thyroid nodule (BTN), and 62 male healthy controls (HCs). Multivariate logistic regression and Cox regression were applied to evaluate the correlation between variables. The performance of serum MMP-9 in diagnosing PTC and predicting structural persistent/recurrent disease (SPRD) during 48 months of follow-up after initial surgery was evaluated by receiving operating characteristic curve analysis. RESULTS: The median serum MMP-9 concentration in the PTC group (79.45 ng/ml) was significantly higher than those in the BTN group (47.35 ng/ml) and HC group (47.71 ng/ml). The area under the curve (AUC) for predicting PTC from BTN was 0.852 at a cut-off value of 60.59 ng/ml. Serum MMP-9 was negatively correlated with disease-free survival (OR 1.026, P=0.001). Serum MMP-9 exhibited good performance in predicting SPRD at a cutoff value of 99.25 ng/ml with an AUC of 0.818. Advanced TNM stage (OR 31.371, P=0.019) and serum MMP-9 ≥99.25 ng/ml (OR 4.103, P=0.022) were independent risk factors for SPRD. CONCLUSIONS: Serum MMP-9 potentially represents a good predictive biomarker for PTC diagnosis and prognosis after thyroidectomy in Chinese male patients for whom radio-imaging indicates suspected PTC.

CREB Protects against Temporal Lobe Epilepsy Associated with Cognitive Impairment by Controlling Oxidative Neuronal Damage.

BACKGROUND: Cognitive dysfunction as a common comorbidity of epilepsy often manifests as learning and memory impairments in patients with temporal lobe epilepsy (TLE). The pathogenetic molecular mechanisms underlying epilepsy-associated cognitive dysfunction are incompletely understood. We investigated the role of cAMP response element binding protein (CREB) and its downstream signaling pathways in the pathogenesis of cognitive impairment in mice with TLE. METHODS: Plasmid vectors of CREB-specific short-hairpin RNAs and CREB cDNA were prepared and transfected into primary neurons. Neuronal apoptosis and mitochondrial oxidative stress were assessed by flow cytometry. For in vivo studies, TLE in mice was induced by pilocarpine injection, and TLE-associated memory decline was evaluated using the Morris water maze after treatment with the CREB inhibitor 666-15, with or without the mitochondria-specific antioxidant MitoQ. CREB and its downstream mediators were examined by Western blotting analysis and quantitative reverse transcription polymerase chain reaction. RESULTS: CREB knockdown induced mitochondrial reactive oxygen species production and apoptosis in primary neurons whereas CREB overexpression brought the opposite effects. The TLE mice exhibited elevated oxidative stress and neuronal apoptosis with decreased expression of CREB and its downstream mediators including PKA, CaMKIV, arc, and c-fos. CREB inhibition exacerbated TLE-associated oxidative neuronal apoptosis and memory decline. MitoQ treatment restored the expression of CREB and its downstream mediators, and prevented TLE-associated oxidative neuronal damage and memory deficits aggravated by CREB inhibition. CONCLUSION: CREB plays a significant role in TLE-associated oxidative neuronal damage and memory impairment. This novel finding provides the evidence of the relationship between CREB and mitochondrial oxidative stress and cognitive dysfunction in epilepsy. Mitochondria-specific antioxidants such as MitoQ may alleviate TLE-associated cognitive dysfunction through activation of CREB and its downstream signaling pathways.

Predictive significance of serum dipeptidyl peptidase-IV in papillary thyroid carcinoma.

BACKGROUND: The significance of serum dipeptidyl peptidase-IV (DPP-IV) in papillary thyroid carcinoma (PTC) has not been elucidated. OBJECTIVE: This study aimed to assess the role of serum DPP-IV in the carcinogenesis and prognosis of PTC. METHODS: The serum DPP-IV concentration was measured in 171 male patients with PTC, 81 male patients with a benign thyroid nodule (BTN), and 52 male healthy controls (HCs). Multivariate logistic regression and Cox regression analyses were performed to evaluate the correlations between variables. Receiver operating characteristic (ROC) curves were used to calculate the diagnosis accuracy. RESULTS: The ROC curve indicated a good performance of DPP-IV for discriminating PTC from BTN, with an area under the curve (AUC) of 0.881 (95% CI, 0.840-0.922). Serum DPP-IV demonstrated a modest performance in predicting nonstructurally persistent disease/recurrent disease (NSPRD) survival, with an AUC of 0.778 (95% CI, 0.635-0.922). A serum DPP-IV level ⩾ 250 nkat/L (HR, 6.529; 95% CI, 2.090-20.398; P= 0.001) and an advanced tumor, lymph node, metastasis (TNM) stage (HR, 4.677; 95% CI, 1.498-14.605; P= 0.008) were found to be independent factors for predicting SPRD. PTC patients with a DPP-IV level ⩾ 250 nkat/L had a worse outcome than those with a DPP-IV level < 250 nkat/L (P< 0.001). CONCLUSIONS: Serum DPP-IV may be a predictive biomarker for PTC diagnosis and prognosis in Chinese male patients.

Novel flavagline-like compounds with potent Fli-1 inhibitory activity suppress diverse types of leukemia.

E26 transformation-specific (ETS) gene family contains a common DNA-binding domain, the ETS domain, responsible for sequence-specific DNA recognition on target promoters. The Fli-1 oncogene, a member of ETS gene family, plays a critical role in hematopoiesis and is overexpressed in diverse hematological malignancies. This ETS transcription factor regulates genes controlling several hallmarks of cancer and thus represents an excellent target for cancer therapy. By screening compounds isolated from the medicinal plant Dysoxylum binectariferum in China, we identified two chemically related flavagline-like compounds including 4'-demethoxy-3',4'-methylenedioxyrocaglaol and rocaglaol that strongly inhibited Fli-1 transactivation ability. These compounds altered expression of Fli-1 target genes including GATA1, EKLF, SHIP1, and BCL2. Consequently, the flavagline-like compounds suppressed proliferation, induced apoptosis, and promoted erythroid differentiation of leukemic cells in culture. These compounds also suppressed erythroleukemogenesis in vivo in a Fli-1-driven mouse model. Mechanistically, the compounds blocked c-Raf-MEK-MAPK/ERK signaling, reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), and inhibited Fli-1 protein synthesis. Consistent with its high expression in myelomas, B-cell lymphoma, and B chronic lymphocytic leukemia (B-CLL), pharmacological inhibition of Fli-1 by the flavagline-like compounds or genetic knock-down via shRNA significantly hindered proliferation of corresponding cell lines and patients' samples. These results uncover a critical role of Fli-1 in growth and survival of various hematological malignancies and point to flavagline-like agents as lead compounds for the development of anti-Fli-1 drugs to treat leukemias/lymphomas overexpressing Fli-1.

Prognostic value of transcranial facial nerve motor-evoked potentials in predicting facial nerve function following cerebellopontine angle tumorectomy.

Facial nerve paralysis is a common complication following cerebellopontine angle (CPA) surgery. This study investigated the prognostic value of facial nerve motor-evoked potentials (FNMEPs) elicited by transcranial electrical stimulation for facial nerve outcome after CPA tumorectomy.A total of 95 patients were enrolled in this study between January 2014 and January 2016. All these patients underwent CPA tumorectomy (unilateral, n = 95; bilateral, n = 1). Intraoperative FNMEP elicited by transcranial electrical stimulation was recorded. The short- and long-term postoperative facial nerve functions were evaluated according to the House-Brackmann (HB) scale. The correlation between perioperative changes in the FNMEP stimulus threshold (delta FNMEP = postoperative stimulus threshold level-preoperative stimulus threshold level) and postoperative facial nerve functions were analyzed.On the first day postoperatively, the facial nerve function was HB grade I in 67, grade II in 17, grade III in 7, and grade IV in 5 facial nerves. One year postoperatively, the facial nerve function was grade I in 80, grade II in 11, grade III in 3, and grade IV in 2 facial nerves. The delta FNMEP was significantly correlated with the short- and long-term facial nerve function; receiver operating characteristic (ROC) curves yielded a cut-off delta FNMEP value of 30 V (sensitivity, 91.3%; specificity, 98.6%) and 75 V (sensitivity, 100%; specificity, 98.8%) for predicting short- and long-term facial nerve function damage, respectively.FNMEP elicited by transcranial electrical stimulation is an effective and safe approach for predicting facial nerve function in CPA tumorectomy. A high delta FNMEP is a potential indicator for the prediction of postoperative facial nerve damage.

Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes.

Breast cancer is one of the main types of cancer affecting the health of females worldwide. Despite improvements in therapeutic approaches, cancer patients succumb to the disease due to metastasis itself, rather than the primary tumor from which metastases arise, emphasizing the need for the better understanding of the biological bases that contribute to disease progression. RAB22A, a member of the proto-oncogene RAS family, plays an important role in the formation, trafficking and metabolism of exosomes, and is associated with the occurrence and development of multiple human cancers. In this study, we demonstrate that the upregulation of RAB22A is associated with breast cancer progression and lymph node metastasis. We identified a signature of RAB22A and miR-193b that exhibited a negative association in metastatic as opposed to the surrounding normal cells, and RAB22A was identified as the target gene of miR-193b. While RAB22A was found to regulate exosomes-mediated breast cancer cell proliferation, invasion and migration, these biological characteristics were diminished in the breast cancer cells in which the RAB22A gene was knocked down or in the cells in which the exosomes were dissolved by proteinase K/RNase treatment. On the whole, the findings of this study demonstrate the critical role that miR-193b plays in the regulation of RAB22A-mediated exosome function during cancer growth and metastasis, which may have significant implications on cancer therapy.

Serum MMP-2 as a potential predictive marker for papillary thyroid carcinoma.

OBJECTIVE: The prevalence of papillary thyroid carcinoma (PTC) is rising rapidly. However, there are no reliable serum biomarkers for PTC. This study aimed to investigate the validity of preoperative serum matrix metalloproteinase-2 (MMP-2) as a biomarker for predicting prognosis of PTC after total or partial thyroidectomy. METHODS: Male patients with PTC or a benign thyroid nodule (BTN) and healthy controls (HCs) were retrospectively included. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance of preoperative serum MMP-2 in diagnosing PTC, predicting lymph node metastasis (LNM), and predicting structurally persistent/recurrent disease (SPRD). Multivariate logistic regression and Cox regression were applied to identify independent risk factors for SPRD. RESULTS: The preoperative serum MMP-2 concentration in the PTC group was higher than those in BTN and HC groups. The concentration of postoperative serum MMP-2 decreased in comparison with pre-operation. ROC curves showed that serum MMP-2 could differentially diagnose PTC from BTN at the cutoff value of 86.30 ng/ml with an area under the curve (AUC) of 0.905 and could predict central LNM (CLNM) at the cutoff value of 101.55 ng/ml with an AUC of 0.711. Serum MMP-2 ≥101.55 ng/ml, age ≥45 years, and advanced TNM stage were independent risk factors for CLNM. Patients with SPRD had a higher median MMP-2 level (149.22 ng/ml) than patients without SPRD (104.55 ng/ml). Serum MMP-2 at the cutoff value of 144.04 ng/ml could predict SPRD in PTC patients with an AUC of 0.803. Advanced TNM stage and serum MMP-2 ≥144.04 ng/ml were independent risk factors for SPRD. Patients with serum MMP-2 ≥144.04 ng/ml had a worse clinical outcome than those with MMP-2 <144.04 ng/ml. CONCLUSION: Preoperative serum MMP-2 may serve as a biomarker for diagnosing PTC and a predictive indicator for LNM and SPRD in male patients with PTC.

Effect of vasopressin on hippocampal injury in a rodent model of asphyxial cardiopulmonary arrest.

The effect of vasopressin on the neuronal injury following the restoration of spontaneous circulation (ROSC) in cardiac arrest (CA) is not yet fully understood. The present study was conducted in order to investigate the effect of vasopressin alone, or in combination with epinephrine, on the ROSC and hippocampal injury in a rat model of asphyxial CA. Asphyxial CA was induced in 144 rats by clamping the tracheal tube, and animals were allocated equally into the following three groups: Treatment with vasopressin (0.8 U/kg); epinephrine (0.2 mg/kg); or vasopressin (0.8 U/kg) plus epinephrine (0.2 mg/kg). An additional 48 rats underwent a sham surgical procedure without asphyxial CA and cardiopulmonary resuscitation. Hippocampal tissue was harvested at 1, 3, 6 and 12 h post-ROSC, and the levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 were determined using immunohistochemistry. In comparison with rats treated with epinephrine alone, higher ROSC success rates were observed in rats treated with vasopressin, or vasopressin plus epinephrine. In addition, treatment with vasopressin attenuated hippocampal injury and reduced hippocampal p38 MAPK and NF-κB expression more efficiently compared with epinephrine alone. In conclusion, treatment with vasopressin exhibits a protective effect in patients experiencing CA, and this may be attributed to the inhibition of p38 MAPK and NF-κB expression.

Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients.

BACKGROUND: Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. OBJECTIVE: The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. METHODS: Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). RESULTS: Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. CONCLUSION: Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

A sensitive and selective LC-MS/MS method for the quantitative determination of segetalin A from the plasma of rats.

A sensitive and selective LC-MS/MS method was developed and validated for the determination and pharmacokinetic investigation of segetalin A in rat plasma. Sample preparation was accomplished through a simple SPE procedure for the removal and preconcentration of the analyte and IS. Plasma samples were separated by HPLC on a Symmetry C18 column using a mobile phase consisting of methanol and 0.1% formic acid in water (70:30, v/v) with isocratic elution. The quantification was performed using multiple reaction monitoring with the transitions m/z 610.3 → 511.2 for segetalin A and m/z 779.4 → 751.4 for IS, respectively. The calibration curve was linear over the range of 8.0-4000 ng/mL with a limit of quantitation (LOQ) of 8.0 ng/mL. This method was applied in a pharmacokinetic study of segetalin A in rats. For intravenous (i.v.) administration, the plasma concentrations of segetalin A decreased quickly (t1/2z, 1.31 ± 0.341 h). For oral administration, the plasma concentrations of segetalin A increased to a peak value at 1.50 ± 0.577 h, followed by a gradual decrease to the LOQ in 12 h. The mean AUC values after i.v. and oral administration were 553 ± 105 and 1482 ± 110 ng h/mL, respectively.

Erythropoietin Protects Rat Brain Injury from Carbon Monoxide Poisoning by Inhibiting Toll-Like Receptor 4/NF-kappa B-Dependent Inflammatory Responses.

Inflammatory responses play critical roles in carbon monoxide (CO) poisoning-induced cerebral injury. The present study investigated whether erythropoietin (EPO) modulates the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) inflammatory signaling pathways in brain injury after acute CO poisoning. EPO (2500 and 5000 U/kg) was injected subcutaneously twice a day after acute CO poisoning for 2 days. At 48 h after treatment, the expression levels of TLR4 and NF-κB as well as the levels of inflammatory cytokines in the hippocampal tissues were measured. Our results showed that CO poisoning induced a significant upregulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat hippocampal tissues. Treatment with EPO remarkably suppressed the gene and protein expression levels of TLR4 and NF-κB, as well as the concentrations of TNF-α, IL-1ß, and IL-6 in the hippocampal tissues. EPO treatment ameliorated CO poisoning-induced histological edema and neuronal necrosis. These results suggested that EPO protected against CO poisoning-induced brain damage by inhibiting the TLR4-NF-κB inflammatory signaling pathway.

Development and validation of a UPLC-MS/MS method for the determination of cucurbitacin B in rat plasma and application to a pharmacokinetic study.

Cucurbitacin B (CuB), one of the most abundant forms of cucurbitacins, is a promising natural anticancer drug candidate. Although the anticancer activity of CuB has been well demonstrated, information regarding the pharmacokinetics is limited. A rapid, selective and sensitive UPLC-MS/MS for CuB was developed and validated using hemslecin A (HeA) as internal standard (IS). Plasma samples were pre-treated by liquid-liquid extraction with dichloromethane. Separation was achieved on a reversed-phase C18 column (50 × 4.6 mm, 5 µm) at 35°C using isocratic elution with water-methanol (25:75, v/v) at a flow rate of 0.3 mL/min. The analytes were monitored by a triple quadrupole tandem mass spectrometer with positive electrospray ionization mode. The calibration curve was linear (r > 0.995) in a concentration range of 0.3-100 ng/mL with a limit of quantification of 0.3 ng/mL. Intra- and inter-day accuracy and precision were validated by percentage relative error and relative standard deviation, respectively, which were both lower than the limit of 15%. This assay was successfully applied to a pharmacokinetic study of CuB in Wistar rats.